This article has been updated. Latest update 27/9/2022.
Statistics from the adverse event databases have been updated along with the sections about India, about vaccinating children and adolescents, about variants, and about vaccine ‘passports’ and certificates.
- The Pfizer-BioNTech, AstraZeneca-Oxford, Moderna vaccines are being administered under emergency use authorisations in the UK. The UK regulator has also approved use of the Janssen Biotech, Nuvaxovid, and Valneva vaccines under conditional marketing authorisations.
- The Moderna vaccine, the Covid-19 vaccine developed by the Johnson & Johnson subsidiary Janssen Biotech, and the Novavax Covid-19 vaccine are being administered in the US under emergency use authorisations. The FDA approved the Biologics Licence Application submitted by BioNTech for the mRNA BNT162b2 vaccine.
- Documents from the Pfizer file that the FDA has released in response to a Freedom of Information Act request and a court order can be found here.
- The European Commission has granted conditional marketing authorisations for the Pfizer-BioNTech, AstraZeneca-Oxford, Moderna, Janssen Biotech, and Nuvaxovid vaccines.
- The Therapeutic Goods Administration in Australia has granted the Pfizer-BioNTech, AstraZeneca, Moderna, and Novavax vaccines provisional approval.
- Nine Covid vaccines are approved in India, seven for restricted emergency use and two under a conditional marketing authorisation.
- Vaccine manufacturers are seeking strategies to combat virus variants.
- Covid vaccine booster doses are being administered in dozens of countries.
- The WHO’s VigiBase, VAERS, EudraVigilance, and other databases in the UK, Australia, and France list hundreds of thousands of reported adverse reactions after Covid vaccination, including thousands of deaths. Adverse reactions include heart inflammation, Bell’s palsy, and Guillain-Barré syndrome.
- The Pfizer-BioNTech and Moderna Covid vaccines have been authorised in the US for children from six months of age.
- There are concerns that there may be disease enhancement with some vaccines.
- Covid vaccination ‘passports’ or certificates were introduced in numerous countries and regulations limiting access to certain places and facilities to those who have been vaccinated became rapidly widespread.
- There have been protests against vaccine mandates and the segregation of the non-vaccinated.
Covid vaccination drives are continuing around the world, mostly under emergency use authorisations.
According to the Our World in Data website, about 12.68 billion Covid vaccine doses have been administered worldwide. About 4.12 million doses are administered every day and 67.9% of the world’s population has received at least one dose.
As politicians, health authorities, and a mostly enthusiastic public express joy and relief at what they view as the beginning of the end of the pandemic, sceptics point to the growing number of adverse reactions after Covid vaccination, the risks of long-term adverse effects, and the lack of conclusive evidence that vaccination is preventing SARS-CoV-2 infection and virus spread.
There is particular disquiet about DNA and RNA vaccines, which have never previously been approved for human use.
The World Health Organisation’s global pharmacovigilance database, VigiBase, lists more than 4.3 million individual case reports of adverse reactions following Covid vaccination, including more than 21,500 deaths.
Pfizer’s own post-authorisation analysis shows that, as of February 28, 2021, there had been 42,086 reports of suspected adverse reactions to its Covid-19 vaccine (158,893 individual-symptom events). The reports included 1,223 deaths. (Further details here.)
The first temporary authorisation for emergency supply of the Pfizer-BioNTech vaccine was given on December 1, 2020.
The global death toll from Covid-19 is now put at more than 6.5 million.
Differences in viewpoints about Covid vaccination, and particularly about the implementation of Covid vaccine certificates and mandatory vaccination, have caused relationship breakdowns, including traumatic splits in families.
Those who have chosen not to receive a Covid vaccination are shamed and the hesitant are pressured. Financial and other incentives to encourage people to get a Covid vaccination became rapidly widespread.
Most mainstream journalists dismiss or condemn all vaccine hesitancy as wrong and, on social media, serious abuse is levelled at those who argue that they have the right to refuse Covid vaccination. Employers increasingly made Covid vaccination a requirement for their staff.
There have been demonstrations in numerous countries against vaccine mandates and the restrictions imposed on the non-vaccinated. In Australia, police fired on demonstrators with rubber bullets, and protestors and journalists were injured by tear gas and pepper sprays.
Those, including the US president, Joe Biden, who said the world was in a “pandemic of the unvaccinated” are being challenged more strongly than ever now that the vaccinated are being infected in large numbers by the Omicron variant, which spreads far more rapidly and easily than the original SARS-CoV-2 and other variants.
The definition of ‘fully vaccinated’ is changing all the time and, in some countries, it no longer means double-vaccinated, it means having also received a third dose or booster.
The director of the Centers for Disease Control and Prevention (CDC) in the US, Rochelle Walensky, said that fully vaccinated still meant two doses of the Moderna or Pfizer vaccines or one dose of the Janssen vaccine.
She added that the CDC was working to “pivot the language to make sure that everybody is as up to date with their Covid-19 vaccines as they personally could be– should be – based on when they got their last vaccine”.
The CDC now states on its website: “You are up to date with your Covid-19 vaccines when you have received all doses in the primary series and all boosters recommended for you, when eligible.
It says that people are considered “fully vaccinated” two weeks after their second dose in a two-dose series, such as in the case of the Pfizer-BioNTech and Moderna vaccines, or two weeks after the single-dose J&J/Janssen vaccine.
Speaking about the Omicron variant during an interview with Yahoo Finance on January 10, 2022, the CEO of Pfizer, Albert Bourla, said: “We know that the two doses of a vaccine offer very limited protection, if any. The three doses with a booster, they offer reasonable protection against hospitalisation and deaths.”
Bourla said during a healthcare conference on the same day that Pfizer and BioNTech were working on a vaccine that specifically targetted Omicron and one that included the previous vaccine and one targetting Omicron.
A new bivalent Pfizer-BioNtech vaccine, which targets the BA.4 and BA.5 Omicron variants, has since been authorised in the US for use as a single 30-microgram booster dose for individuals 12 years of age and older.
On September 16, 2022, the European Medicines Agency (EMA) announced that its Committee for Medicinal Products for Human Use (CHMP) had recommended converting the conditional marketing authorisations for Pfizer-BioNTech’s Comirnaty vaccine and Moderna’s Spikevax to full (standard) marketing authorisations for administration of the vaccines to people aged 12 years and above who have received at least a primary course of Covid vaccination.
“These no longer need to be renewed annually,” the EMA said. “All other obligations for the companies remain in place.”
The EMA said the CHMP’s recommendation “covers all existing and upcoming adapted Comirnaty and Spikevax vaccines, including the recently approved adapted Comirnaty Original/Omicron BA.1, Comirnaty Original/Omicron BA.4/5 and Spikevax bivalent Original/Omicron BA.1.”
The European Commission (EC) will review the CHMP’s recommendations and is expected to make a final decision soon.
On September 1, 2022, the CHMP recommended that Nuvaxovid should be authorised as a booster dose for adults who have had Nuvaxovid, an mRNA vaccine, or an adenoviral vector vaccine as their primary vaccination.
New mucosal Covid vaccines administered via inhalation have been approved in India and China and have also been developed in Iran and Cuba.
The Russian Health Ministry has meanwhile registered an intranasal version of the Sputnik V Covid vaccine.
CanSino Biologics announced in September 2022 that the National Medical Products Administration of China (NMPA) had granted the company approval for its ‘Recombinant COVID-19 Vaccine (Adenovirus Type 5 Vector) for Inhalation’, marketed as Convidecia Air, to be used as a booster dose administered through the mouth.
The same adenovirus vector is used for Convidecia Air as for the intramuscular version of the vaccine, Convidecia.
In India, Bharat BioTech has received approval for its adenovirus vectored vaccine BBV154, which is administered via the nose.
There is widespread misunderstanding among the general public about what vaccine efficacy means and many people misguidedly believe that, once vaccinated, they can cast aside their masks and hug their relatives and friends without risk. There remain many uncertainties about how effective Covid-19 vaccines are in preventing the transmission of SARS-CoV-2, not least since the emergence of the Omicron variant.
The main efficacy percentages initially vaunted by the front-running manufacturers related to the number of confirmed cases of Covid-19 that occurred during the trials and an analysis of how many of those cases occurred among those vaccinated and how many were among those who received a saline placebo or, in the case of some of the AstraZeneca-Oxford trials, a meningitis vaccine. The main percentages provided from the trials relate to disease prevention, not the prevention of infection.
Associate editor of The BMJ Peter Doshi wrote in an opinion piece published on November 26, 2020, that Pfizer and Moderna were reporting relative risk reduction rather than absolute risk reduction, which, Doshi said, appeared to be less than 1%.
There are concerns that spike protein vaccines against SARS-CoV-2 carry the risk of pathogenic priming, also known as disease enhancement.
During studies of spike protein vaccines against SARS-CoV-1, the exposure of vaccinated animals to the virus led to increased morbidity and mortality.
There is also worry about mix-and-match experiments and potential problems when people are given one dose of one vaccine followed by a dose of a different one, or two doses of one vaccine and a booster of a different one.
The co-authors of a study on the safety of mRNA Covid-19 vaccines that called for full transparency of Covid-19 vaccine clinical trial data have written an open letter to Albert Bourla and the CEO of Moderna, Stéphane Bancel.
The seven researchers, who include two medical doctors from the US and Peter Doshi, published the letter in The BMJ on August 31, 2022, as a Rapid Response to an article by Jennifer Block entitled ‘Covid-19: Researchers face wait for patient level data from Pfizer and Moderna vaccine trials’, published in The BMJ on July 12, 2022.
The researchers’ study of serious adverse events in the Pfizer and Moderna phase 3 Covid-19 vaccine trials was published in the peer-reviewed journal Vaccine.
“The results showed the Pfizer and Moderna both exhibited an absolute risk increase of serious adverse events of special interest (combined, 1 per 800 vaccinated), raising concerns that mRNA vaccines are associated with more harm than initially estimated at the time of emergency authorisation,” Doshi et al. wrote.
“We acknowledge that our estimates are only approximations because the original data remain sequestered. For example, we could not stratify by age, which would help clarify the populations in which benefits outweigh harms.”
A more definitive determination of the actual harms and benefits required individual participant data (IPD) that remained unavailable to research investigators, Doshi et al. added.
“In the summer of 2020, before results from the trials were announced, vaccine manufacturers were criticised for keeping the trial protocols secret. In response, the protocols were released. Yet the same did not happen for the trial data,” the researchers wrote.
“Unlike its European counterpart, the US regulator FDA does hold electronic IPD datasets, and in a meeting to discuss our study last March, we requested they repeat our analysis using IPD, but to our knowledge, this has not occurred. With the publication of our study, we have written the FDA again to reiterate our request.”
Doshi et al. added: “Covid-19 vaccines are now among the most widely disseminated medicines in the history of the world. Yet, results from the pivotal clinical trials cannot be verified by independent analysts.
“The public has a legitimate right to an impartial analysis of these data. Covid vaccinations have cost taxpayers tens of billions of dollars, perhaps even rivalling the annual NIH budget for all aspects of biomedical and behavioural research.”
Block noted in her article that independent researchers looking to obtain patient level data from the Pfizer and Moderna Covid-19 vaccine trials may now have to wait longer.
“In status reports filed recently with the US federal trials registry (clinicaltrials.gov) between February and May, both companies extended the dates by which the trials will be completed, Pfizer by nine months, from 15 May 2023 to 8 February 2024. Moderna’s expected completion date is delayed from 27 October to 29 December 2022,” she wrote.
Results from the study by Doshi et al.
In August 2022, health and risk communication researcher and health journalist Yaffa Shir-Raz broke the story of a cover-up by the Israeli Ministry of Heath of findings about adverse reactions to Covid vaccination.
Shir-Raz said a leaked video revealed that, in June 2022, researchers in a team led by the head of the clinical pharmacology and toxicology unit at the Shamir Medical Centre, Mati Berkowitz, presented findings to the health ministry that indicated long-term effects from Covid vaccination, including some not listed by Pfizer, and a causal relationship.
“The ministry published a manipulative report, and told the public that no new signal was found,” she added.
Shir-Raz tweeted on September 2:
🇮🇱In a leaked video, a research team commissioned by the Israeli MoH warns: "We’ll have to think medical-legal – how to present our findings to avoid lawsuits. Why? Because of quite a few side effects we said: 'OK, it exists and reports exist, BUT STILL GET VACCINATED'". pic.twitter.com/IgXavuYaSH
— Yaffa Shir-Raz (@YaffaRaz) September 1, 2022
She added: “In the zoom meeting, which took place in early June, the research team reports to MoH senior staff on its findings regarding the safety of the Pfizer vaccine, based on an analysis of SE reports received from Dec. 2021 to May 2022 from a new reporting system launched Dec 2021.”
4/Nevertheless, the IMOH withheld the findings for 2 months, even from their own expert committee which decided 3 weeks later to clear the vaccine for infants. Only on August 9, two months later, the IMoH decided to publish a formal report: https://t.co/9GS8QHAAcU pic.twitter.com/RYtAOEJtb8
— Yaffa Shir-Raz (@YaffaRaz) September 1, 2022
She said that, in contrast to the researchers’ findings and conclusions presented to it, the ministry “blatantly claimed in the report that there were no new signals found in the study that are not already known”.
Shir-Raz also said the ministry manipulated the reporting rate of adverse events by using a denominator of the total number of doses given in Israel for the entire year and a half since the beginning of the vaccine rollout: about 18 million doses.
The new reporting system was launched in December 2021 when the majority of Israelis had already got two to three vaccine doses, which meant that adverse events reported in the study were an underrepresentation, she said.
She says the ministry hid the fact that they only instituted the system in December 2021, and that the analysis was done on reports received during the six months until May 2022, from one small health maintenance organisation (HMO).
“This manipulation – using the denominator of the total doses, was repeated in each of the categories of the side effects in the report,” she wrote.
She tweeted: “Even worse! They calculated the denominator of vaccines against the reports of menstrual irregularities using TOTAL NUMBER OF ADULT DOSES – meaning, men were included in the equation of how common menstrual irregularities were,” she tweeted.
“And if all this is not enough, the MoH also framed the findings as representing the ENTIRE POPULATION, hiding the fact that only one small HMO out of the 4 operating in Israel handed over their reports, thus the study only covers ~15% of the population.”
Shir-Raz notes that the researchers only analysed the five most common groups of adverse effects: neurological injuries, general adverse effects, menstrual irregularities, musculoskeletal system disorders, and digestive system/kidney and urinary system disorders. There were 17 other categories, including cardiovascular events, which were the 6th most common, that they had not yet analysed.
The researchers found many cases of re-challenge – a recurrence or worsening of an adverse effect following repeated doses of the vaccine. They identified cases of re-challenge in all the five most common categories of adverse reactions.
Shir-Raz also notes that, since the beginning of the vaccination campaign in Israel, many Israeli experts have expressed serious concerns regarding the ability of the health ministry to monitor the safety of Covid vaccination and provide reliable data to the world.
She quotes professor Retsef Levy from the Massachusetts Institute of Technology (MIT) as saying during a VRBPAC meeting that Israel’s Covid vaccination monitoring system was dysfunctional.
“Only at the end of December 2021, a year after starting the vaccine rollout did the MoH finally institute a proper system, to coincide with the rollout of Covid-19 vaccines in children aged five–11,” Shir-Raz wrote.
Cardiologist Dr Aseem Malhotra has published a landmark paper (Part 1 and Part 2) about mRNA Covid vaccines. A strong advocate of Covid vaccination in the past, Malhotra now writes: “It cannot be said that the consent to receive these agents was fully informed, as is required ethically and legally. A pause and reappraisal of global vaccination policies for Covid-19 is long overdue.”
After lengthy research Malhotra now says: “There is a strong scientific, ethical and moral case to be made that the current Covid vaccine administration must stop until all the raw data has been subjected to fully independent scrutiny.”
He is convinced that his own father’s cardiac arrest and death in July 2021 were caused by Covid vaccination.
“As far as I’m concerned, the evidence is overwhelming,” Malhotra said. “This vaccine does have a strong link with increasing cardiac arrest, risk and cardiac death.”
Malhotra points to Pfizer’s own trial data. He says the company stated that there were four cardiac arrests in the vaccinated cohort and one in the control group. “When you put it all together, it makes a very strong case that there is a clear link between this particular vaccine and increasing cardiac risk,” Malhotra said in an interview with James Freeman.
Malhotra says his review of evidence from randomised trials and real world data relating to Covid mRNA vaccines indicates that, in the non-elderly population, the number of people who would need to be vaccinated so as to prevent a single death from Covid-19 ran into the thousands.
“Re-analysis of randomised controlled trials using the messenger ribonucleic acid (mRNA) technology suggests a greater risk of serious adverse events from the vaccines than being hospitalised from Covid-19,” Malhotra writes in his new paper.
He says there is a “pandemic of misinformed doctors and a misinformed and unwittingly harmed public” and writes that “coercively mandating these Covid-19 vaccinations” has been a “particularly egregious mis-step, especially in the light of clear indicators suggesting that the use of these pharmaceutical interventions –especially in younger age groups – should have been suspended”.
He added: “Authorities and sections of the medical profession have supported unethical, coercive, and misinformed policies such as vaccine mandates and vaccine passports, undermining the principles of ethical evidence-based medical practice and informed consent.”
Malhotra told Freeman that the Pfizer Covid vaccine caused myocarditis in up to one in 2,700 people and that recent data from Israel published in one of Nature’s Scientific Reports showed that there had been a 25% increase in heart attacks or cardiac arrests in people aged between 16 and 39 years that was not linked to Covid, but was “absolutely linked to mRNA vaccines”.
The current system is “encouraging good people to do bad things”, Malhotra says.
Malhotra says he realised that there was something particularly sinister going on when Covid vaccination was mandated.
“The root of this problem are very powerful corporations that have too much influence on government, on health care, on media, and their primary responsibility is to produce profit for their shareholders, not to give you the best treatment.” Malhotra said.
He added: “This has been well documented, that these corporations unfortunately, and the way that they go about their business, by misleading people, by their business model being fraud, they act like psychopaths and they are a psychopathic entity.
“Ultimately the conclusion is that we have a psychopathic entity influencing health policy and that needs to stop and it needs to stop now.”
Malhotra said that his father, who was a doctor himself and had been vice-president of the British Medical Association, was a very fit and well 73-year-old, who, during the whole of lockdown, was walking 10,000 to 15,000 steps a day.
“He was very conscientious of his diet,” Malhotra said. “I had assessed his heart a few years earlier. And in fact he actually had improved his lifestyle since then.
“But his post mortem findings really shocked me. There were two severe blockages in his coronary arteries which didn’t really make any sense, with everything I know both as a cardiologist (someone who has an expertise in this particular area), but also intimately knowing my dad’s lifestyle and his health.”
Malhotra says that, not long after his father’s death, data started to emerge that suggested there was a possible link between the MMR vaccine and an increased risk of heart attacks “from a mechanism of increasing inflammation around the coronary arteries”.
He says he was then contacted by a whistleblower in a very prestigious university in the UK, a cardiologist himself, who explained that there were similar research findings in his department, but the researchers had essentially decided to cover them up because they were worried about losing research funding from the pharmaceutical industry.
Global vaccination drives
In the United States, where Covid vaccination began on December 14, 2020, more than 612 million doses have been given so far.
In the UK, where Covid vaccination began on December 8, 2020, more than 151 million doses have been administered.
In China, about 3.44 billion Covid vaccine doses are reported to have been administered. More than 175 million doses are reported to have been administered in Russia.
India started administering Covid vaccinations on January 16, 2021, and about 2.16 billion doses have been administered so far.
Brazil started administering the CoronaVac vaccine, developed by the Chinese company Sinovac Biotech, on January 17, 2021, and, since then, more than 471 million Covid vaccine doses have been administered.
The Seychelles, Israel, the United Arab Emirates, and Bahrain are the four countries that vaccinated their populations the fastest.
Israel saw a sharp drop in daily mortality and infection rates and the number of Covid-19 patients in serious condition dropped below 100 on May 3, 2021. However, on June 25, the authorities reimposed an indoor mask requirement after more than two hundred new Covid-19 cases were recorded the day before. This was the highest daily total recorded since April 7. The health ministry also called on Israelis to wear face coverings when attending mass gatherings outdoors and urged people in at-risk groups to avoid gatherings altogether.On July 16, the health ministry reported 1,118 new cases of Covid-19, which was the highest daily number in nearly four months.
On July 21, the number of active Covid-19 cases was 9,134. The number of patients in a serious condition had risen to 75 and the death toll had increased to 6,457, the ministry said.
On September 14, worldometers.info, put the number of active cases at 83,316 and the number of deaths at 7,433. A total 690 patients were reported to be seriously ill with Covid-19.
By October 1, the number of active cases had fallen to 45,412 and the number of serious or critical cases had gone down to 586. The death toll was 7,766.
By January 25, 2022, there were 615,247 active cases, 732 of which were serious or critical, and the death toll was 8,488.
The total 16,115 SARS-CoV-2 infections diagnosed on January 5 was the highest number of new infections reported in a single day since the start of the Covid-19 pandemic. A total 12,554 cases were reported on January 4.
At the end of July 2021, Israel started giving a third booster dose to people aged 60 years and above who were vaccinated with a second dose more than five months earlier. On August 13, eligibility for a third vaccine dose was extended to those aged over 50 years and younger people employed in geriatric and health care institutions, or who suffer from underlying medical conditions.
On August 29, Israel made booster doses of the Covid-19 vaccine available to everyone age 12 and up who received the second shot at least five months earlier. As of September 11, more than two million Israelis had received a third dose.
On December 31, the country started its rollout of a fourth Covid vaccine dose, which is being administered to people with weakened immune systems along with elderly residents and employees in care homes.
A team of Israeli researchers said in August that their findings indicated a “strong effect of waning immunity” in all age groups six months after administration of the Pfizer-BioNTech vaccine.
In a preprint published on medRxiv on August 30, 2021, Yair Goldberg et al. said that quantifying the effect of waning immunity on vaccine effectiveness was “critical for policy makers worldwide facing the dilemma of administering booster vaccinations”.
They said the results presented in their paper were the basis of the decision by Israel’s Ministry of Health to give a third dose of Covid-19 vaccine to people aged 60 or over who had been vaccinated at least five months previously.
The researchers explained that, after a period with almost no SARS-CoV-2 infections, a resurgent Covid-19 outbreak began mid-June 2021.
“Possible reasons for the breakthrough were reduced vaccine effectiveness against the Delta variant, and waning immunity,” they wrote.
The researchers analysed data on all the positive PCR test results between July 11 and 31, 2021, from Israeli residents who were fully vaccinated before June 2021.
They looked at the infection rates and severe Covid-19 outcomes for people who were vaccinated in different time periods.
“We extracted from the database all documented SARS-CoV-2 infections diagnosed in the period in which the Delta variant was dominant, and the severity of the disease following infection,” the researchers wrote.
“The rates of both documented SARS-CoV-2 infections and severe Covid-19 exhibit a statistically significant increase as time from second vaccine dose elapsed.”
“Elderly individuals (60+) who received their second dose in March 2021 were 1.6 (CI: [1.3, 2]) times more protected against infection and 1.7 (CI: [1.0, 2.7]) times more protected against severe Covid-19 compared to those who received their second dose in January 2021.”
Data analysed related to 4,785,245 people, of whom 12,927 had a positive PCR test and 348 deteriorated to a severe condition.
The researchers refer to a paper about the longer-term follow-up of participants in the Phase 2/3 randomised trial of the Pfizer-BioNTech vaccine in which a reduction in vaccine efficacy from 96% (as of seven days to less than two months after vaccination) to 90% (as of two months to less than four months after vaccination) and 84% (as of four months to about seven months after vaccination) was reported.
“There is also a preliminary report of waning effectiveness of the same vaccine from a health maintenance organisation in Israel, and evidence of a decay in vaccine-induced neutralisation titres during the first six months following the second dose,” Goldberg et al. wrote.
The researchers say that, in contrast to early findings from the UK, in Israel about two thirds of the cases of severe Covid-19 during the study period were among people who received two doses of the Pfizer-BioNTech vaccine.
“Two major differences exist between the vaccination policies of Israel and the UK,” Goldberg et al. added. “First, the current analysis used data from July 2021, a time when, for the majority of the Israeli population, at least five months passed from the second dose to the outbreak of the Delta variant.
The UK data were collected during April–June 2021 with a much shorter time from vaccination to the outbreak, the researchers said.
“Second, Israel has followed the original Pfizer protocol of administering the second dose three weeks after the initial vaccination in the vast majority of recipients, while in the UK the time between doses has been typically longer,” they added.
Data released by Israel’s health ministry in July 2021 indicated that close to 40% of people who developed Covid-19 during the most recent outbreak were vaccinated, according to local media.
Of more than 7,700 new cases, 3,000 were in patients who had been vaccinated, according to media reports. Just 72 cases were in people who had previously been infected with SARS-CoV-2.
According to a report from Israel’s health ministry released on July 21, 2021, the Pfizer-BioNTech vaccine was, on average, only 39% effective against SARS-CoV-2 infection and 40.5% effective in preventing symptomatic Covid-19.
The report said the vaccine provided 88% protection against hospitalisation from Covid-19 and 91.4% protection against severe Covid-19 illness.
The report also indicated waning protection against SARS-CoV-2 infection, showing just 16% effectiveness against infection transmission among those who received a second dose in January 2021, 44% effectiveness for those vaccinated in February, 67% effectiveness if the second dose was received in March, and 75% for those vaccinated in April.
Other Israeli data showed that, among those aged over 65 years, there were 69 serious cases of Covid-19 per million people among those vaccinated and 72 serious cases per million people among the non-vaccinated. It was also reported that about 90 per cent of new confirmed Covid-19 cases in those aged over 50 years were in people who were fully vaccinated.
In the Seychelles, there was a surge in Covid cases in May 2021 and restrictions, including school closures, were reimposed. On June 25, 2021, public health and social measures were reinforced. This was in light of community transmission of SARS-CoV-2, an increasing number of deaths from Covid-19, and confirmation that virus variants were circulating in the population.
In Iceland, a large percentage of those recorded as being SARS-CoV-2 positive were fully vaccinated.
In north Africa, Morocco started its vaccination drive after the delivery of shipments of the BBIBP-CorV vaccine developed by Sinopharm and the AstraZeneca-Oxford vaccine, which is branded as Covishield in India. By July 10, 2022, more than 54.8 million Covid-19 vaccine doses had been administered in Morocco.
Algeria started its Covid vaccination drive on January 30, 2021, administering Russia’s Sputnik V vaccine. By July 10, 2022, more than 15.2 million Covid vaccine doses had been administered.
Egypt began the vaccination of medical staff on January 25, 2021, administering the BBIBP-CorV vaccine at a hospital in the northeastern province of Ismailia.
On May 13, 2021, the country received 1,768,800 doses of the AstraZeneca-Oxford vaccine doses via the COVAX Facility, which is a mechanism established by Gavi, the Vaccine Alliance (GAVI), the global Coalition for Epidemic Preparedness Innovations (CEPI), and the WHO that aims to provide governments with early access to Covid vaccines produced by multiple manufacturers. A month earlier, the country received its first shipment containing 854,400 doses.
By July 10, 2022, more than 91.4 million Covid vaccine doses had been administered in Egypt.
On February 4, 2021, the Palestinian Authority received 10,000 doses of the Sputnik V vaccine and, on March 29, it received 100,000 doses of Sinopharm’s Covid-19 vaccine, donated by China.
UNICEF said that, on March 17, the authority had received the first shipment of 37,440 doses of the Pfizer-BioNTech vaccine and 24,000 doses of the AstraZeneca-Oxford vaccine from the COVAX Facility. Further consignments of COVAX vaccine doses were planned to cover 20 per cent of the Palestinian population of approximately 1 million people, UNICEF said, and all consignments were for both the West Bank and the Gaza Strip.
The Palestinian Authority began vaccinating health workers in the occupied West Bank on February 2, 2021, after receiving 5,000 doses of the Moderna vaccine from Israel and, as of July 10, 2022, more than 3.7 million Covid vaccine doses had been administered in Palestine.
About 320,000 doses of the Pfizer-BioNTech vaccine were allocated to four African countries – Cabo Verde, Rwanda, South Africa and Tunisia.
The vaccine received WHO emergency use approval, but countries were required to be able to store and distribute doses at minus 70 degrees Celsius.
In addition to the vaccines being supplied by the COVAX Facility, the African Union secured 670 million vaccine doses for the continent.
The FDA has authorised booster doses of the Pfizer-BioNTech, Moderna, and Janssen Covid vaccines. The Pfizer-BioNTech booster is now authorised for children and adolescents aged 12 to 17 years. The Moderna and Janssen vaccines are authorised for individuals aged 18 years and older.
On January 3, 2022, the FDA said the time between the completion of primary vaccination with the Pfizer-BioNTech vaccine and a booster dose should be shortened from six months to at least five months. Rochelle Walensky endorsed the change.
On January 7 the agency also amended the emergency use authorisation (EUA) for the Moderna vaccine to shorten the time between the completion of a primary series and a booster dose to at least five months. The Moderna single booster dose is half of the dose that is administered in the primary series.
The booster interval recommended for people who have received the Janssen vaccine is still two months.
In November 2021 the FDA amended the EUAs to authorise use of a single booster dose for all individuals aged 18 years and above at least six months after the completion of primary vaccination with the Moderna or Pfizer-BioNTech vaccines or at least two months after the completion of primary vaccination with the Janssen Biotech Covid vaccine.
Administration of boosters was previously recommended only for specific groups of people such as those aged 65 years or above and 18- to 64-year-olds who were at high risk of developing severe Covid-19.
On January 5, 2022, the CDC’s Advisory Committee on Immunization Practices (ACIP) voted 13–one in favour of Pfizer-BioNTech boosters for children and adolescents aged 12 to 17 years and Rochelle Walensky endorsed the recommendation.
In making its decision to revise the interval between the Modern primary vaccination series and the booster, the FDA said it had inferred that that the safety data on the five-month interval for booster doses obtained in the population in Israel, vaccinated with the Pfizer-BioNTech vaccine, could apply to the Moderna vaccine.
The agency said it had reviewed real world evidence on the safety of booster doses provided by the Israeli Ministry of Health, which included data from about 4.1 million third (booster) doses of the Pfizer-BioNTech vaccine given to individuals 16 years of age and older at least five months after the primary series, and, the FDA said, “did not raise new safety concerns associated with the booster dose”.
The FDA said that, although the overall composition of the Moderna vaccine was different to the Pfizer-BioNTech vaccine, both were mRNA vaccines “with safety and efficacy profiles that, though not identical, are relatively similar”.
The agency added: “Acknowledging the differences, it is reasonable to make the inference that the safety data on the five-month interval for booster doses obtained in the population in Israel can apply to the Moderna Covid-19 Vaccine.”
It said that, “based on the totality of the scientific evidence available”, it had concluded that a homologous booster dose of the Moderna vaccine “may be effective” and that the known and potential benefits of the booster dose “outweigh the known and potential risks in individuals 18 years of age and older when given at least five months following the primary series”.
The FDA said that peer-reviewed data from multiple laboratories indicated that a booster dose of the Pfizer-BioNTech vaccine greatly improved an individual’s antibody response to be able to counter the Omicron variant.
“Authorising booster vaccination to take place at five months rather than six months may therefore provide better protection sooner for individuals against the highly transmissible Omicron variant,” the agency added.
The CDC has since stated that people aged 12 years and above who are moderately or severely immunocompromised may choose to receive a second booster dose of an mRNA Covid-19 vaccine at least four months after the first booster dose.
While most people receiving a primary series of Covid vaccination with an mRNA vaccine receive two doses, people with suppressed immune systems usually get three doses, so a second booster would be a fifth dose.
The CDC also stated that all adults aged 50 years and above can receive a second booster dose of an mRNA Covid-19 vaccine at least four months after the first booster dose.
Pfizer and BioNTech had only applied to the FDA for emergency use authorisation for an additional booster for adults aged 65 years and older who had received an initial booster dose of any of the authorised or approved Covid-19 vaccines.
The companies said their submission was based on two real-world data sets from Israel analysed at a time when the Omicron variant was widely circulating.
They cited an analysis of Israeli Ministry of Health records relating to 1.1 million adults aged 60 years and older who had no known history of SARS-CoV-2 infection and were eligible for an additional booster (fourth dose).
“These data showed rates of confirmed infections were two times lower and rates of severe illness were four times lower among individuals who received an additional booster dose of the Pfizer-BioNTech Covid-19 Vaccine administered at least four months after an initial booster (third) dose compared to those who received only one booster dose,” the companies said.
The companies also cited a clinical trial in Israel involving healthcare workers aged 18 years of age and above who had received three doses of the Pfizer-BioNTech vaccine.
In the case of 154 participants who received an additional dose at least four months after the initial booster, neutralising antibody titers increased approximately seven- to eight-fold at two and three weeks after the fourth dose compared to five months after the initial booster, they said.
“Additionally, there was an eight-fold and ten-fold increase in neutralising antibody titres against the Omicron variant (B.1.1.529) at one and two weeks after the additional booster dose, respectively, compared to five months after the initial booster,” the companies added.
Pfizer and BioNTech said that emerging evidence, including data from Kaiser Permanente Southern California (KPSC), suggested that effectiveness against both symptomatic Covid-19 and severe disease caused by Omicron waned three to six months after receipt of an initial booster dose.
The CDC and the FDA made their new decisions about boosters without calling meetings of their advisory panels of outside experts.
The FDA has authorised use of each of the available Covid-19 vaccines as a heterologous (‘mix-and-match’) booster dose for eligible people after completion of primary vaccination with a different available Covid-19 vaccine.
The ACIP had earlier voted against recommending a booster dose for people who are at high risk of SARS-CoV-2 infection or transmission because of their occupation or setting.
The committee said the administration of booster doses should be limited to people aged 65 and older, long-term residents of care facilities, and certain people with underlying medical conditions.
However, Rochelle Walensky overruled the ACIP’s recommendation and aligned CDC policy with the FDA’s EUA amendment.
On September 17, 2021, the Vaccines and Related Biological Products Advisory Committee (VRBPAC) in the US had voted unanimously in favour of Pfizer-BioNTech Covid vaccine boosters for people aged 65 years or above and individuals who are at high risk of developing severe Covid-19.
The committee had earlier voted by 16 members to two against booster shots being made available to all those aged 16 years and above.
In August 2022 the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK issued a conditional marketing authorisation in Britain for a Moderna bivalent booster vaccine (mRNA-1273.214) that is aimed at the original strain of SARS-Cov-2 and the Omicron BA.1 subvariant, which the European Centre for Disease Prevention and Control (ECDC) has classified as a de-escalated variant.
The ECDC de-escalated BA.1 because it was being detected at extremely low levels in the EU/EEA.
The original strain of SARS-CoV-2 is no longer circulating.
The MHRA also issued a temporary Regulation 174 authorisation for Northern Ireland for the new booster.
The authorisations are for people aged 18 years and above.
One 0.5-millilitre dose contains 25 micrograms of Covid-19 mRNA vaccine elasomeran, embedded in SM-102 lipid nanoparticles, and 25 micrograms of the Covid-19 mRNA vaccine imelasomeran, also embedded in SM-102 lipid nanoparticles.
“Imelasomeran is a single-stranded mRNA, 5’-capped, encoding a full-length, codon-optimised pre-fusion stabilised conformation variant (K983P and V984P) of the SARSCoV-2 spike (S) glycoprotein (Omicron variant, B.1.1.529),” the MHRA said.
The MHRA points out in the summary of product characteristics for the new booster that there is an increased risk for myocarditis and pericarditis following the administration of the original Moderna Covid-19 vaccine and the new bivalent Original/Omicron vaccine.
“These conditions can develop within just a few days after vaccination and have primarily occurred within 14 days,” the MHRA said.
“They have been observed more often after the second dose, and more often in younger males.”
The new booster vaccine has been authorised after extremely limited testing.
In the summary of product characteristics the MHRA provides pages of data from trials of the original Moderna Covid-19 vaccine, but, with regard to the new vaccine, it points out that testing is ongoing and refers to a study involving just 814 participants.
The agency states: “The safety, reactogenicity, and immunogenicity of a second booster dose of Spikevax bivalent Original/Omicron are evaluated in an ongoing Phase 2/3 open-label study in participants 18 years of age and older (mRNA-1273-P205).
“In this study, 437 participants received the Spikevax bivalent Original/Omicron 50 microgram booster dose, and 377 participants received Spikevax (original) 50 microgram booster dose.”
The MHRA said the new booster had a reactogenicity profile similar to that of the original vaccine given as a second booster dose.
It said the frequency of adverse reactions after administration of the new vaccine was also similar to that of a first booster dose of 50 micrograms of the original Moderna booster and “relative to” the second dose of the original Moderna primary series (100 micrograms).
The agency said that no new safety signals had been identified.
Pfizer-BioNTech’s bivalent booster targetting the original SARS-CoV-2 strain and Omicron BA.4 and BA-5 was authorised across the EU following an EC decision on September 12.
The Pfizer-BioNTech and Moderna bivalent boosters targetting the original SARS-CoV-2 strain and Omicron BA.1 were authorised across the EU following an EC decision on September 1.
On August 29, the Therapeutic Goods Administration (TGA) in Australia provisionally approved Moderna’s mRNA-1273.214 for use as a booster dose in adults 18 years and over.
On August 31, the FDA amended the EUAs for the Moderna and Pfizer-BioNTech Covid-19 vaccines to authorise bivalent formulations for use as a single booster dose at least two months following primary or booster vaccination.
The Moderna bivalent vaccine mRNA-1273.222, which targets the Omicron variants BA.4 and BA.5, is authorised for use as a single 50-microgram booster dose for individuals 18 years of age and older. The Pfizer-BioNTech bivalent vaccine, which also targets the BA.4 and BA.5 variants, is authorised for use as a single 30-microgram booster dose for individuals 12 years of age and older.
The FDA said that the bivalent vaccines included an mRNA component of the original SARS-CoV-2 strain “and an mRNA component in common between the omicron variant BA.4 and BA.5 lineages”.
Moderna said its application for an EUA was based on preclinical data “as well as clinical trial data available for the company’s BA.1 Omicron-targeting bivalent booster candidate, mRNA-1273.214”.
A phase 2/3 trial for mRNA-1273.222 was currently underway, the company said.
The new Pfizer bivalent booster was authorised without any human trial being conducted.
In the case of the bivalent boosters, Pfizer-BioNTech and Moderna test for antibody levels but not for the vaccines’ efficacy against Covid infection or severe Covid disease.
Pfizer and BioNTech said their application to the FDA followed guidance from the agency to include clinical data from the companies’ bivalent Omicron BA.1-adapted vaccine and pre-clinical and manufacturing data from the companies’ bivalent Omicron BA.4/BA.5-adapted vaccine “.
“The bivalent vaccine contains mRNA encoding the original SARS-CoV-2 spike protein, which is present in the original Pfizer-BioNTech Covid-19 vaccine, together with mRNA encoding the spike protein of the Omicron BA.4/BA.5 variant,” the companies said.
“Pre-clinical data showed a booster dose of Pfizer and BioNTech’s Omicron BA.4/BA.5-adapted bivalent vaccine generated a strong neutralising antibody response against Omicron BA.1, BA.2 and BA.4/BA.5 variants, as well as the original wild-type strain.
“A clinical study investigating the safety, tolerability and immunogenicity of the Omicron BA.4/BA.5-adapted bivalent vaccine in individuals 12 years of age and older is expected to start this month.”
The FDA said that the monovalent mRNA Covid-19 vaccines were no longer authorised as booster doses for individuals aged 12 years and above.
On September 26, Pfizer and BioNTech announced that they had completed a submission to the FDA for emergency use authorisation for a 10-microgram booster dose of its ‘Omicron BA.4/BA.5-adapted’ bivalent Covid-19 vaccine for children aged five to 11 years.
The companies said their request for an EUA was supported by safety and immunogenicity data from the companies’ bivalent ‘Omicron BA.1-adapted vaccine’, non-clinical and manufacturing data from the companies’ 10-microgram bivalent ‘Omicron BA.4/BA.5-adapted vaccine’, and pre-clinical data.
An application to extend the marketing authorisation for the bivalent vaccine to include children aged five to 11 years would be submitted to the European Medicines Agency in the coming days, the companies said.
Pfizer and BioNTech also said they had initiated a Phase 1/2/3 study to evaluate the safety, tolerability, and immunogenicity of different doses and dosing regimens of their ‘Omicron BA.4/BA.5-adapted’ bivalent vaccine in children aged six months to 11 years.
The Pfizer-BioNTech announcement followed one by Moderna on September 23 stating that it had submitted requests for FDA emergency use authorisation of its mRNA-1273.222 bivalent booster for adolescents aged 12 to 17 years and children aged six to 11 years.
The company said its application FDA authorisation for the vaccine for children aged six months to under six years was expected to be completed later this year.
At the VRBPAC meeting on June 28, 2022, the vice-president for Viral Vaccines Vaccine Research and Development at Pfizer, Kena Swanson, presented data obtained from a study of eight mice who were vaccinated with the original Pfizer Covid vaccine as a booster and the new bivalent booster.
Pfizer says the mice showed an increased response to all the Omicron variants tested, including BA.4 and BA.5.
At the June 28 VRBPAC meeting the committee members voted 19–2 to recommend inclusion of a SARS-CoV-2 Omicron component for Covid-19 booster vaccines.
One of the two members who voted against recommending the inclusion of the Omicron component was Paul Offit, who is the chair of vaccinology at the University of Pennsylvania’s Perelman School of Medicine.
Offit told the Journal of the American Medical Association (JAMA): “It is not reasonable to assume that data generated for an Omicron BA.1 vaccine can easily be extrapolated to BA.4 and BA.5.
“These new Omicron subvariants are highly transmissible. Therefore, they will require a very high level of neutralising antibodies present at the time of exposure to prevent symptomatic infection.”
Henry Bernstein, who also voted against recommending the addition of an Omicron component to Covid boosters, told JAMA: “There was no compelling evidence that adding that new element to the vaccine was going to increase vaccine effectiveness.”
On September 1, the ACIP voted 13 to 1 in favour of authorising the two new boosters and Rochelle Walensky endorsed the committee’s decision very quickly.
The CDC said that, in the coming weeks, it expected to recommend updated Covid-19 boosters for other pediatric groups, “per the discussion and evaluation of the data by ACIP on Sept. 1, 2022”.
The FDA announced on July 29 that the US Department of Health and Human Services (HHS), in collaboration with the Department of Defence, had agreed to purchase 66 million doses of Moderna’s mRNA-1273.222 booster “for potential use in the fall and winter”.
The agency said the purchase was in addition to the 105 million bivalent Covid-19 vaccine booster doses the US government had already purchased from Pfizer.
The FDA said that, in the absence of additional Covid-19 funding from Congress, the administration “was forced to pull $10 billion from critical Covid-19 response efforts in order to pay for additional vaccines and treatments”.
The funding for the most recent agreement with Moderna came from that reallocated funding, the FDA said.
On August 18, 2021, public health and medical experts from the US Department of Health and Human Services (HHS) in the US had said a booster Covid-19 vaccine shot would be needed “to maximise vaccine-induced protection and prolong its durability”.
Rochelle Walensky; the acting commissioner for the Food and Drug Administration (FDA), Janet Woodcock; and the director of the National Institutes of Health (NIH), Francis Collins, were among those who jointly issued a statement about the planned booster doses.
They said: “The available data make very clear that protection against SARS-CoV-2 infection begins to decrease over time following the initial doses of vaccination, and, in association with the dominance of the Delta variant, we are starting to see evidence of reduced protection against mild and moderate disease.
“Based on our latest assessment, the current protection against severe disease, hospitalisation, and death could diminish in the months ahead, especially among those who are at higher risk or were vaccinated during the earlier phases of the vaccination rollout. For that reason, we conclude that a booster shot will be needed to maximize vaccine-induced protection and prolong its durability.”
On October 15, 2021, the VRBPAC voted unanimously to recommend emergency use authorisation for a booster dose of the Janssen Covid vaccine for adults aged 18 years and older at least two months following initial vaccination.
The committee also recommended that the FDA grant an EUA for a 50-microgram booster dose of the Moderna vaccine for people aged 65 and older, those aged 18 to 64 years who are at high risk of severe Covid-19, and people aged 18 to 64 years whose exposure to Covid-19 puts them at risk for Covid-19 complications or severe illness. The vote was unanimous.
Moderna said that neutralising antibody titres had waned prior to boosting, particularly against variants of concern, at approximately six months. “Notably, a booster dose of mRNA-1273 at the 50 µg dose level boosted neutralising titres significantly above the Phase 3 benchmark,” the company s said. “After a booster dose, a similar level of neutralising titres was achieved across age groups, notably in older adults (ages 65 and above).”
On August 13, 2021, Moderna had announced that the FDA approved an update to the EUA for the Moderna Covid vaccine to include a 100-microgram booster for immunocompromised individuals in the US aged 18 years or older who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.
On September 9, 2021, the MHRA in the UK said that the Pfizer-BioNTech and AstraZeneca-Oxford vaccines could be used as “safe and effective booster doses”.
The MHRA’s chief executive, June Raine, said it would now be for the UK’s Joint Committee on Vaccination and Immunisation (JCVI) to advise on whether booster vaccinations would be given and if so, which vaccines should be used.
“We know that a person’s immunity may decline over time after their first vaccine course. I am pleased to confirm that the Covid-19 vaccines made by Pfizer and AstraZeneca can be used as safe and effective booster doses,” Raine said.
Britain’s Health and Social Care Secretary, Sajid Javid, said on September 1 that he had accepted the JCVI’s recommendation that a third vaccine dose should be offered to people aged 12 and above who have severely weakened immune systems.
The JCVI said: “Until more data is available, any provision of a third primary dose to persons who are immunosuppressed will draw on the assumption that a third dose is unlikely to confer significant harms or disadvantages, but may offer the possibility of benefit.
“These uncertainties in harms and benefits will need to be communicated as part of informed consent, and expectations regarding the value of a third primary dose taken into account.”
The committee said that, for people aged 18 years and above, it advised a preference for mRNA vaccines for the third primary dose, with the option of the AstraZeneca-Oxford vaccine for people who had received that vaccine previously “where this would facilitate delivery”.
The JCVI added that, “in exceptional circumstances”, people who had previously received an mRNA Covid vaccine could be offered a third primary dose of the AstraZeneca-Oxford vaccine following a decision by a health professional on a case-by-case, individualised basis. For those aged 12 to 17 years, the Pfizer-BNT162b2 vaccine remained the preferred choice, the JCVI said.
The British government announced on September 14 that a Covid vaccine booster programme, using the Pfizer-BioNTech vaccine, would begin soon for the over-50s along with vulnerable people, including frontline health workers.
On November 15, the JCVI announced that it was advising that all adults aged 40 to 49 should also be offered a booster vaccination with an mRNA Covid-19 vaccine six months after their second dose, irrespective of the vaccines given for the first and second doses.
The JCVI added that the booster doses should preferably be either a Pfizer-BioNTech vaccine dose or a half dose of the Moderna vaccine.
“Future considerations include the need for booster vaccination (third dose) for 18- to 39-year-olds who are not in an at-risk group, and whether additional booster vaccination (fourth dose) for more vulnerable adult groups may be required,” the committee said.
The committee also advised that all 16- and 17-year-olds be given a second dose of the Pfizer-BioNTech vaccine. Previously, only 16- and 17-year-olds who are considered to be in an at-risk group were eligible.
Second doses for 16- and 17-year-olds should be given at least 12 weeks after completion of their initial vaccination, the JCVI said.
Sajid Javid said he accepted the JCVI’s advice about the booster doses and the second dose for 16- and 17-year-olds.
Vaccinating children and adolescents
On June 15, 2022, the VRBPAC voted unanimously to recommend that the FDA give emergency use authorisation for the Pfizer-BioNTech and Moderna Covid vaccines to be administered to infants aged six months.
With regard to the Moderna vaccine, the 21-member panel voted on the following question: Based on the totality of scientific evidence available, do the benefits of the Moderna Covid-19 Vaccine when administered as a two-dose series (25 μg each dose) outweigh its risks for use in infants and children six months through five years of age?
With regard to the Pfizer vaccine, the panel voted on the following question: Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech Covid-19 Vaccine when administered as a three-dose series (3 μg each dose) outweigh its risks for use in infants and children six months through four years of age?
On June 18, 12 members of the ACIP also voted unanimously to recommend authorising Covid-19 vaccinations for children aged six months to five years (to 5 years in the case of Moderna and to four years in the case of Pfizer-BioNTech).
The CDC’s director, Rochelle Walensky, rapidly endorsed the ACIP’s recommendation. The CDC said that this expanded eligibility for vaccination to nearly 20 million additional children “and means that all Americans ages six months and older are now eligible for vaccination”.
All children, including children who have already had Covid-19, should get vaccinated, the CDC said. “Distribution of paediatric vaccinations for these younger children has started across the country,” the agency added.
The effectiveness data that Pfizer presented to the FDA to support an EUA for administration of its vaccine to children aged six months to four years was based on a comparison of immune responses following three doses of the vaccine in a subset of children in this age group to the immune responses among teenagers and adults aged 16 to 25 years who received two higher doses of the Pfizer-BioNTech Covid-19 vaccine in a previous study.
The immune response to the vaccine of approximately eighty children aged six to 23 months and approximately 140 children aged from two to four years were compared to the immune response of approximately 170 of the older participants.
“In these FDA analyses, the immune response to the vaccine in both age groups of children was comparable to the immune response of the older participants,” the FDA said.
In the case of the Moderna vaccine the immune responses of a subset of 230 children aged six to 23 months and a subset of 260 children aged two to five years who received a two-dose primary series of the vaccine at 25 micrograms of mRNA per dose were compared to the immune responses among 290 adults aged 18 to 25 years who received two higher doses of the vaccine in a previous study.
The FDA said its analyses indicated that the immune response to the vaccine in both age groups of children was comparable to the immune response of the adults.
On June 14, the VRBPAC voted unanimously to recommend emergency use authorisation for two doses of Moderna’s Covid-19 vaccine to be administered to children aged six years and above.
Moderna had sought an EUA for two 100 μg doses of its vaccine to be administered to adolescents aged 12–17 years, with the doses given one month apart, and for two 50 μg doses to be administered to children aged six–11 years old, with the doses also given one month apart.
On November 2, 2021, the CDC director Rochelle Walensky had endorsed the recommendation from the ACIP that children aged five to 11 years receive the Pfizer-BioNTech Covid vaccine.
The CDC said that two doses of ten micrograms would be administered three weeks apart (30-microgram doses are used for people 12 and older). This was the first time a paediatric Covid vaccination has been recommended in the US.
“CDC now expands vaccine recommendations to about 28 million children in the United States in this age group and allows providers to begin vaccinating them as soon as possible,” the CDC said.
The Pfizer-BioNTech phase 1/2/3 trial initially enrolled 4,500 children aged between six months and 11 years in the US, Finland, Poland, and Spain.
Additional children were enrolled in all age groups following study amendments and the trial eventually included approximately 8,300 children, the companies said.
The companies added that the trial was designed to evaluate the safety, tolerability, and immunogenicity of their vaccine in a two-dose schedule (with doses given about 21 days apart) in three age groups: five- to 11-year-olds, two- to four-year-olds, and children aged between six months and one year.
“Based on the Phase 1 dose-escalation portion of the trial, children ages five to under 12 years received a two-dose schedule of 10 µg each while children under age five received a lower 3 µg dose for each injection in the Phase 2/3 study,” the companies said.
On December 17, 2021, Pfizer and BioNTech announced that the companies would test a third three-microgram dose given at least two months after the second dose in children aged under five years and a third dose of the ten-microgram formulation in children aged between five and 11 years.
The companies said two doses of the vaccine generated a strong immune response in children aged between six and 24 months, but not in the cohort of children aged two to four years.
“Compared to the 16- to 25-year-old population in which high efficacy was demonstrated, non-inferiority was met for the 6- to 24-month-old population, but not for the 2- to under 5-year-old population in this analysis,” Pfizer and BioNTech said.
The ACIP voted 14-0 in favour of use of the Pfizer-BioNTech Covid vaccine for 5- to 11-year-olds.
On October 29, the FDA had authorised emergency use of the Pfizer-BioNTech vaccine for five- to 11-year-olds in the US.
The FDA’s decision followed a vote at the VRBPAC meeting on October 26. The VRBPAC members voted 17–0, with one abstention, in favour of granting an EUA for the Pfizer-BioNTech vaccine for five- to 11-year-olds. There are 28 million children in this age group in the US.
Statement on abstention from Michael Kurilla, who is the director of the Division of Clinical Innovation at the NIH’s National Center for Advancing Translational Sciences:
Pfizer said that, if the Pfizer-BioNTech vaccine was authorised and recommended by the ACIP, it would be the first Covid-19 vaccine available for five- to 11-year-olds in the US.
“The companies expect to then begin shipping pediatric vaccine doses immediately, as directed by the US government,” Pfizer said.
The company said that Pfizer and BioNTech had submitted requests for authorisation of use of their Covid-19 vaccine for five- to 11-year-olds to other regulators around the world, including the EMA.
The organisation Children’s Health Defense (CHD), which was founded by lawyer and environmentalist Robert F. Kennedy, Jr said on October 25 that it would take legal action against the FDA if the agency granted the EUA.
Kennedy and CHD board member Meryl Nass wrote in a letter addressed to the VRBPAC chairman, Arnold Monto, committee members, and all FDA staff: “CHD will seek to hold you accountable for recklessly endangering this population with a product that has little efficacy but which may put them, without warning, at risk of many adverse health consequences, including heart damage, stroke, and other thrombotic events and reproductive harms.”
On January 3, 2022, the FDA amended the emergency use authorisation for the Pfizer-BioNTech vaccine to make it available as a booster for 12- to 15-year-olds.
The agency said it had determined that the protective health benefits of a single booster dose of the Pfizer-BioNTech vaccine “to provide continued protection against Covid-19 and the associated serious consequences that can occur including hospitalisation and death” outweighed the potential risks in 12- to 15-year-olds.
The FDA said it had reviewed real-world data from Israel, including safety data from more than 6,300 12- to 15-year-olds who received a booster dose of the Pfizer-BioNTech vaccine at least five months after completion of the primary two-dose vaccination series.
“The data shows there are no new safety concerns following a booster in this population,” the FDA said. “There were no new cases of myocarditis or pericarditis reported to date in these individuals.”
After the ACIP voted 13–one in favour of Pfizer-BioNTech boosters for children and adolescents aged 12 to 17 years Rochelle Walensky endorsed the recommendation.
The FDA also authorised a third primary series dose for certain immunocompromised children aged five to 11 years of age and Walensky endorsed the change.
The CDC said that, consistent with its prior recommendation for adults, it was recommending that moderately or severely immunocompromised five- to 11-year-olds receive an additional primary dose of vaccine 28 days after their second shot.
“At this time, only the Pfizer-BioNTech Covid-19 vaccine is authorised and recommended for children aged five–11,” the CDC added.
The FDA said: “Children five through 11 years of age who have undergone solid organ transplantation, or who have been diagnosed with conditions that are considered to have an equivalent level of immunocompromise, may not respond adequately to the two-dose primary vaccination series. Thus, a third primary series dose has now been authorised for this group.”
The potential effectiveness of an additional vaccine dose for five- to 11-year-olds was extrapolated from data in adults, the FDA added.
“The agency used prior analyses conducted as part of the authorisation process for healthy children to inform safety in this population and determined that the potential benefits of the administration of a third primary series dose at least 28 days following the second dose of the two-dose regimen, outweighed the potential and known risks of the vaccine,” the FDA added. “To date, the FDA and CDC have seen no new safety signals in this age group.”
On May 17, 2022, the FDA amended the EUA for the Pfizer-BioNTech Covid-19 Vaccine, authorising the use of a single booster dose for administration to all children aged five to 11 years at least five months after completion of a primary vaccination series with the Pfizer-BioNTech vaccine.
FDA commissioner Robert M. Califf said: “While it has largely been the case that Covid-19 tends to be less severe in children than adults, the Omicron wave has seen more kids getting sick with the disease and being hospitalised, and children may also experience longer term effects, even following initially mild disease.”
The director of the FDA’s Center for Biologics Evaluation and Research, Peter Marks, said: “Since authorising the vaccine for children down to five years of age in October 2021, emerging data suggest that vaccine effectiveness against Covid-19 wanes after the second dose of the vaccine in all authorised populations.”
The FDA said the EUA for a booster dose of the Pfizer-BioNTech vaccine for five- to 11-year-olds was based on the FDA’s analysis of immune response data in a subset of children from the ongoing trial that supported the October 2021 authorisation of the primary vaccination series in the age group.
“Antibody responses were evaluated in 67 study participants who received a booster dose seven to nine months after completing a two-dose primary series of the Pfizer-BioNTech Covid-19 Vaccine,” the FDA said.
“The antibody level against the SARS-CoV-2 virus one month after the booster dose was increased compared to before the booster dose.”
The FDA did not hold a meeting of its Vaccines and Related Biological Products Advisory Committee to discuss the new amendment of the EUA.
The agency had previously convened the committee “for extensive discussions regarding the use of booster doses of Covid-19 vaccines”, the FDA said.
“After review of Pfizer’s EUA request, the FDA concluded that the request did not raise questions that would benefit from additional discussion by committee members,” the agency added.
On May 18, Rochelle Walensky endorsed the ACIP’s vote (11–1 with one abstention) in favour of giving five- to 11-year-olds the boosters at least five months after their second dose.
On December 18, Pfizer and BioNTech reported on the trial in which it was evaluating the safety, tolerability, and immunogenicity of its Covid-19 vaccine when administered to children aged six months to four years.The companies said there was shown to be a weaker immune response for the two- to four-year-olds than for the younger children.
“Compared to the 16- to 25-year-old population in which high efficacy was demonstrated, non-inferiority was met for the 6- to 24-month-old population but not for the 2- to under 5-year-old population in this analysis,” the companies said.
The companies also initiated a “low dose sub-study” of a third dose of 10 or 30 micrograms in approximately 600 adolescents aged 12 to 17 years.
On September 20, Pfizer and BioNTech announced results of the phase 2/3 trial involving children aged five to 11 years. The companies said the vaccine was “safe, well tolerated and showed robust neutralising antibody responses”.
“The antibody responses in the participants given 10 µg doses were comparable to those recorded in a previous Pfizer-BioNTech study in people 16 to 25 years of age immunised with 30 µg doses,” the companies said.
“The ten-microgram dose was carefully selected as the preferred dose for safety, tolerability and immunogenicity in children five to 11 years of age.”
Side effects from the vaccine were generally comparable to those observed in participants 16 to 25 years of age, the companies said.
Pfizer and BioNTech said that the SARS-CoV-2–neutralising antibody geometric mean titre (GMT) was 1,197.6 (95% confidence interval [CI, 1106.1, 1296.6]), “demonstrating strong immune response in this cohort of children one month after the second dose”.
This, the companies said, compared well (was non-inferior) to the GMT of 1146.5 (95% CI: 1045.5, 1257.2) from participants aged 16 to 25 years old, who were used as the control group for the analysis and who were administered a two-dose, 30-microgram regimen.
While there is a 4% difference between the GMTs for the age groups, the fact that the GMT for the younger age group lies within the confidence interval of the GMT of the 16- to 25-year-olds studied means that, statistically, there is a possibility that both groups could have the same GMT.
Reporting for STAT news, Matthew Herper pointed out that Pfizer and BioNTech provided only an average antibody level. “That could mean that some kids would have lower levels – and less protection,” he wrote.
Herper quoted William Gruber, a senior vice-president of vaccine clinical research and development at Pfizer, as saying that antibody levels were high throughout the group studied.
“Pfizer’s press release did not include any data on the extent to which the vaccine reduced the chances that children would become sick,” Herper added.
“Gruber said that there were not enough cases of illness to tell. But outside experts said it was reasonable to assume that similar levels of antibodies would mean similar protection from disease.”
Outside experts viewed the data as positive, but limited, Herper wrote.
Seventy-six, scientists, doctors, and other healthcare professionals in the UK have written to the country’s health regulator and health secretary, urging them not to rollout Covid-19 vaccination for young children.
The medical professionals and scientists say they “strongly challenge the addition of COVID-19 vaccination into the routine child immunisation programme despite no demonstrated clinical need, known and unknown risks and the fact that these vaccines still have only conditional marketing authorisation”.
The say that “the balance of benefit and risk which supported the rollout of mRNA vaccines to the elderly and vulnerable in 2021 is totally inappropriate for small children in 2022”.
They have written to June Raine; the chairman of the JCVI COVID-19 vaccines sub-committee, Lim Wei Shen; the Chief Medical Officer for England, Chris Whitty; the CEO of the UK Health Security Agency (UKHSA), Jenny Harries; and the Secretary of State for Health and Social Care, Sajid Javid.
The medical professionals and scientists list the reasons why they say the UK must not follow the US in authorising Covid vaccinations for young children.
“We would urge you to consider very carefully the move to vaccinate ever younger children against SARS-CoV-2 despite the gradual but significant reducing virulence of successive variants, the increasing evidence of rapidly waning vaccine efficacy, the increasing concerns over long-term vaccine harms, and the knowledge that the vast majority of this young age group have already been exposed to SARS-CoV-2 repeatedly and have demonstrably effective immunity,” they write.
The doctors and scientists say that young healthy children are at minimal risk from Covid-19, especially since the arrival of the Omicron variant.
“The vaccines are of brief efficacy, have known short- to medium-term risks and unknown long-term safety,” they write.
“Data for clinically useful efficacy in small children are scant or absent. In older children, for whom the vaccines are already licensed, they have been promoted via ethically dubious schemes to the potential detriment of other, and vital, parts of the childhood vaccination programme.
“For a tiny minority of children for whom the potential for benefit clearly and unequivocally outweighed the potential for harm, vaccination could have been facilitated by restrictive licences. Whether following the precautionary principle or the instruction to First Do No Harm, such vaccines have no place in a routine childhood immunisation programme.”
The 76 medical professionals and scientists are highly critical of the data presented by Pfizer in support of its request for approval of its vaccine for administration to children aged six months to four years.
“Astonishingly, the results were based on just three participants in the younger age group (one vaccinated and two placebo) and just seven participants in the older two- to four-year-olds (two vaccinated and five placebo),” they write.
“Indeed, for the younger age group the confidence intervals ranged from minus-367% to plus-99%. The manufacturer stated that the numbers were too low to draw any confident conclusions. Moreover, these limited numbers come only from children infected more than seven days after the third dose.”
One of the letter’s signatories, Dr Clare Craig, points out that there were six children, aged two to four years, who had severe Covid-19 in the vaccine group, but only one in the placebo group.
“So on that basis, the likelihood that this vaccine is actually causing severe Covid is higher than the likelihood that it isn’t. There was actually one child who was hospitalised in this trial. They had a fever and a seizure. They had been vaccinated,” Craig said.
Craig accuses Pfizer of twisting the trial data. “They vaccinated the children and they waited three weeks after the first dose before the second dose. In that three-week period, 34 of the vaccinated children got Covid and only 13 in the placebo group, which worked out as a 30% increased chance of catching COVID in that three-week period if you were vaccinated. So they ignored that data.
“And then there was an eight-week gap between the second dose and the third dose where again, children were getting plenty of Covid in the vaccine arm. So they ignored that data.”
Craig says that, in the end, Pfizer ignored 97% of the Covid-19 that occurred during the trial.
She and her fellow letter signatories say that, over the whole trial time period, 225 children tested positive for SARS-CoV-2 infection in the vaccinated cohort as compared with 150 in the placebo group, “giving a calculated vaccine efficacy of only 25% (14% for the six–23 months, and 33% for 2–4s).
“The additional immunogenicity studies against Omicron, requested by the FDA, only involved a total of 66 children tested one month after the third dose,” the letter signatories add.
“It is incomprehensible that the FDA considered that this represents sufficient evidence on which to base a decision to vaccinate healthy children. When it comes to safety, the data are even thinner: only 1,057 children, some already unblinded, were followed for just two months.”
On February 24, 2022, the EMA announced that its human medicines committee had recommended granting “an extension of indication” for the Moderna vaccine to include administration to children aged 6 to 11 years. The vaccine had already been approved for people aged 12 and above.
The dose for six- to 11-year-olds would be 50 micrograms (half the dose administered to people aged 12 and above). Two doses would be given, four weeks apart.
“A main study in children aged six to 11 showed that the immune response to the lower dose of Spikevax (50 µg) was comparable to that seen with the higher dose (100 µg) in 18- to 25-year-olds, as measured by the level of antibodies against SARS-CoV-2,” the EMA said.
The EMA said the most common side effects in children aged six to 11 years were similar to those in people aged 12 and above. They included pain, redness and swelling at the injection site, tiredness, headache, chills, nausea, vomiting, swollen or tender lymph nodes under the arm, fever, and muscle and joint pain.
The CHMP also recommended that a booster dose of Comirnaty may be given “where appropriate” to children and adolescents from 12 years of age.
In September 2022 the CHMP recommended approval for Comirnaty as a 10-microgram booster dose given at least six months after completion of a primary series for children aged five to 11 years.
A primary course of Comirnaty has been authorised in the EU for administration to adolescents aged 16 to 17 years since February 2021 and for children and adolescents aged 12 years and above since May 2021. It was subsequently authorised for administration to five- to 11-year-olds.
In announcing the CHMP’s recommendation that the Moderna vaccine should be authorised for 12- to 17-year-olds, the EMA said on July 23, 2021, that the effects of the vaccine had been investigated in a study involving 3,732 children and adolescents aged 12 to 17 years.
The agency said the study showed that the vaccine produced a comparable antibody response in 12- to 17-year-olds to that seen in young adults aged 18 to 25 years (as measured by the level of antibodies against SARS-CoV-2).
“In addition, none of 2,163 children receiving the vaccine developed Covid-19 compared with four of 1,073 children given a dummy injection,” the EMA said.
The CHMP said that, given the limited number of children and adolescents included in the study, the trial could not have detected new uncommon side effects or estimated the risk of known side effects such as myocarditis and pericarditis.
“However, the overall safety profile of Spikevax determined in adults was confirmed in the adolescent study,” the EMA said. “The CHMP therefore considered that the benefits of Spikevax in children aged 12 to 17 outweigh the risks, in particular in those with conditions that increase the risk of severe Covid-19.”
The most common adverse effects in 12- to 17-year-olds were similar to those experienced by people aged 18 and above, the EMA said.
“They include pain and swelling at the injection site, tiredness, headache, muscle and joint pain, enlarged lymph nodes, chills, nausea, vomiting, and fever,” the agency added.
These effects were usually mild or moderate and improved within a few days, the EMA said.
On August 17, the MHRA extended its conditional marketing authorisation for the Moderna vaccine to allow its use in Britain for 12- to 17-year-olds.
The Moderna vaccine was already authorised for use for 12- to 17-year-olds in Northern Ireland under the CMA extension granted by the EMA on July 23.
On April 14, the MHRA approved the Moderna vaccine for administration to six- to 11-year olds. The vaccine is approved for administration to children aged six to 11 years in Northern Ireland under the updated authorisation granted by the EMA on March 2.
The UK government had said on February 16, 2022, that Covid vaccination would be offered to all children aged five to 11 years. This followed similar announcements in Scotland, Wales, and Northern Ireland.
Sajid Javid said he had accepted guidance from the JCVI that all five- to 11-year-olds should be able to receive the Pfizer-BioNTech vaccine.
The JCVI said: “Although this age group is generally at very low risk of serious illness from the virus, a very small number of children who get infected do develop severe disease.”
The JCVI said it had advised “a non-urgent offer” of two ten microgram doses of the Pfizer-BioNTech paediatric vaccine to five- to 11-year-olds who are not in a clinical risk group. There should be an interval of at least 12 weeks between doses, the JCVI said. (In December 2021 the JCVI had already recommended that the Pfizer-BioNTech vaccine be offered to at-risk 5- to 11-year-olds and this rollout began at the beginning of February 2022.)
The committee said its intention in extending its recommendation to all 5- to 11-year-olds was to “increase the immunity of vaccinated individuals against severe Covid-19 in advance of a potential future wave of Covid-19″.
The JCVI added: Vaccination of children aged 5 to 11 who are not in a clinical risk group is not expected to have an impact on the current wave of Omicron infection. The potential benefits from vaccination will apply mainly to a future wave of infection; the more severe a future wave, the greater the likely benefits from vaccination. Conversely, the less severe a future wave, the smaller the likely benefits from vaccination.”
The committee said it considered its advice about vaccinating 5- to 11-year olds who are not in a clinical risk group as a “one-off pandemic response programme” and added: “As the Covid-19 pandemic moves further towards endemicity in the UK, JCVI will review whether, in the longer term, an offer of vaccination to this, and other paediatric age groups, continues to be advised.”
On December 5, 2021, the TGA in Australia announced that it had provisionally approved the Pfizer-BioNTech vaccine for children aged five to 11 years. The rollout began on January 10, 2022.
“This decision follows the provisional approvals granted by the TGA to Pfizer for the use of Comirnaty in individuals 12 years and older on 22 July 2021 and the booster dose for use in adults 18 years and older on 26 October 2021,” the TGA said when announcing the approval.
The administration said five- to 11-year-olds would be given a lower dose than that given to people aged 12 years and older (10 micrograms instead of 30 micrograms). The vaccine would be supplied in an orange vial rather than the grey or purple vials used to supply the higher dose and would be given in two doses at least three weeks apart.
“Provisional approval of this vaccine is valid for two years and means it can now be legally supplied in Australia,” the TGA said. “The approval is subject to certain strict conditions, such as the requirement for Pfizer to continue providing information to the TGA on longer term efficacy and safety from ongoing clinical trials and post-market assessment.”
On July 19, 2022, the TGA said it had provisionally approved a paediatric dose of the Moderna COVID-19 vaccine for administration to children aged six months to five years.
The TGA said the vaccine should be administered as two doses at least 28 days apart. “The paediatric vaccine is made in the same way as the vaccines for older persons, however it contains a lower concentration of the active ingredient,” the administration said.
The administration said children aged six months to five years would receive 25 micrograms of the vaccine in a 0.25ml vial, those aged six to 11 years will receive 50 micrograms in a 0.25ml vial, and those aged 12 years and older would receive 100 micrograms in a 0.5ml vial.
The Moderna vaccine had already been provisionally approved for children and adolescents aged six years and above (a primary series of two doses administered at least 28 days apart) and it is also provisionally approved as a booster dose for adults aged 18 years and older.
On August 3, however, the ATAGI said it was only recommending Covid-19 vaccination for children aged 6 months to under five years who had severe immunocompromise or disability, and those who had complex and/or multiple health conditions that increased the risk of severe Covid-19.
The ATAGI said it was taking into account the very low risk of severe Covid-19 (e.g. hospitalisation due to Covid-19) in healthy children aged six months to under five years.
“This age group is one of the least likely age groups to require hospitalisation due to Covid-19,” the group said. “Among the small number who are hospitalised or who die due to Covid-19, underlying medical conditions or immunocompromise are frequently present.”
The ATAGI reiterated its previous recommendation that all children aged five years or above should receive a two-dose course of Covid-19 vaccination, but said it did not currently recommend Covid-19 vaccination for children aged six months to under five years who were not in the above risk categories for severe Covid-19.
“Data on benefits in children with complex medical issues or severe immunocompromise are currently limited, but vaccination is recommended based on first principles and evidence of benefit in other age groups,” the group added.
The ATAGI said that up to one in four children in the six -months to under-five-years age group had a fever following administration of the Moderna vaccine, with higher rates seen in those with a history of previous Covid-19.
“As fever in this age group can sometimes result in medical review and/or investigations, and occasionally trigger a febrile convulsion, the side effect profile for this vaccination needs to be considered in the risk-benefit discussion,” the group added.
“There is insufficient evidence to suggest that vaccination of infants and children would impact community transmission.”
In announcing the new provisional approval the TGA said that it had carefully considered data from the KidCOVE clinical trial, which was conducted at multiple sites throughout Canada and the US and included more than 6,000 participants aged six months to six years.
“The study demonstrated that the immune response to the vaccine in children was similar to that seen in young adults (18 to 25 years) with a favourable safety profile,” the TGA said.
The TGA said that most adverse events seen in clinical trials in children aged six months to six years were mild to moderate and were generally reported after the second dose.
They included irritability and/or crying, redness and/or swelling at the injection site, fatigue, fever, muscle pain, and axillary (groin) swelling or tenderness.
The TGA added that provisional approval of the vaccine for children aged six months to five years was valid for two years.
Moderna would be required to continue providing information to the TGA on longer term efficacy and safety from ongoing clinical trials and post-market assessment, the administration added.
The Australian government said on February 23, 2022, that it had accepted advice from the ATAGI to make the Moderna vaccine available for children aged six years and older from February 24. The vaccine was at that time already available to children and adolescents aged 12 years and above.
The TGA approved the administration of Moderna to children aged six years and above on February 17.
For children aged between six and 11 years, the paediatric dose of Moderna is half the dose currently provided for people aged 12 years and above: two 50-microgram doses administered eight weeks apart, or three doses for immunocompromised children.
The government said the recommended eight-week interval could be shortened to four weeks for children at risk of moderate to severe Covid-19, for example those with underlying health conditions. The interval could also be shortened in the case of a Covid-19 outbreak or before international travel, the government added.
The Comirnaty children’s formulation is the only Covid-19 vaccine approved for five-year-olds in Australia and no Covid vaccines are currently approved for children four years of age and under in the country.
In Denmark, since July 1, 2022, it has no longer been possible for children and young people under the age of 18 to get the first Covid vaccination, and, from September 1, 2022, it will no longer be possible to get the second vaccination.
The Danish Health Authority said: “Children and young people only very rarely become seriously ill from Covid-19 with the Omicron variant.
“Quite a few children with a particularly increased risk of a serious course will still have the option of vaccination, after an individual assessment by a doctor.”
Sweden’s Public Health Agency said on January 27, 2022, that the medical benefit for the individual child with a general vaccination against Covid-19 for children aged five–11 years was currently small.
“Therefore, for the spring term 2022 the authority is not recommending general vaccination of children under 12 years of age in Sweden,” the agency said.
“A general vaccination from the age of five is also not expected to have any major effect on the spread of infection at present, neither in the group of children aged 5–11 nor among other groups in the population.”
The director-general of the agency, Karin Tegmark Wisell, said: “We will continue to follow the issue. We are constantly assessing the state of knowledge and the development of the pandemic in Sweden and the rest of the world, and a new position will be taken on this issue before the autumn term.”
The health agency said that children were at a significantly lower risk of developing severe Covid-19 disease compared with adults.
“In general, the younger the child, the lower the risk,” the agency said. “Since the end of October 2021, the Swedish Public Health Agency has been recommending general vaccination against covid-19 from the age of 12 in Sweden. This is based on the benefit to the individual child.”
Covid-19 vaccination is approved in Sweden for children from the age of five years, and has been recommended since the end of December 2021 for children between the ages of five and 11 who are particularly susceptible to respiratory infections.
The FDA expanded the emergency use authorisation for the Pfizer-BioNTech vaccine to include adolescents aged 12 to 15 years on May 10, 2021. It was the first authorisation in the US for use of a Covid vaccine for this age group.
The FDA said it had determined that the vaccine had met the statutory criteria to amend the EUA, and that “the known and potential benefits of this vaccine in individuals 12 years of age and older outweigh the known and potential risks, supporting the vaccine’s use in this population”.
The administration said that from March 1, 2020 to April 30, 2021, approximately 1.5 million Covid-19 cases in individuals aged 11 to 17 years had been reported to the CDC.
“Children and adolescents generally have a milder Covid-19 disease course as compared to adults,” the FDA said.
The Pfizer-BioNTech vaccine would be administered to 12- to 15-year-olds as a series of two doses, three weeks apart as in the case of people aged 16 years and above, the FDA said.
The FDA said that immune response to the vaccine in 190 participants aged between 12 and 15 was compared to the immune response of 170 participants aged between 16 and 25 years.
“In this analysis, the immune response of adolescents was non-inferior to (at least as good as) the immune response of the older participants,” the FDA said.
The FDA said it conducted an analysis of cases of Covid-19 occurring seven days after the second vaccine dose among participants aged between 12 and 15 years.
“In this analysis, among participants without evidence of prior infection with SARS-CoV-2, no cases of Covid-19 occurred among 1,005 vaccine recipients and 16 cases of Covid-19 occurred among 978 placebo recipients,” the FDA said.
The FDA said it concluded that, based on the available data “it is reasonable to believe” that the Pfizer-BioNTech vaccine “may be effective in individuals 12 through 15 years of age”.
Pfizer said the FDA based its decision on data from a Phase 3 clinical trial in which 2,260 participants aged 12 to 15 years were enrolled.
Results from the trial were were published in The New England Journal of Medicine on May 27.
A total 2,260 children aged 12 to 15 years of age received two injections, 21 days apart, of 30 micrograms of BNT162b2 or a placebo (1,131 children received BNT162b2 and 1,129 received a placebo).
Robert W. Frenck, Jr et al. said that BNT162b2 had a “favourable safety and side-effect profile”, with mainly transient mild-to-moderate reactogenicity. The side effects were predominantly injection-site pain (in 79 to 86% of participants), fatigue (in 60 to 66% of participants), and headache (in 55 to 65% of participants). There were no vaccine-related serious adverse events and few overall severe adverse events, the researchers said.
Among the 1,983 trial participants who could be evaluated, and did not have evidence of previous SARS-CoV-2 infection, no cases of Covid-19 with an onset of seven or more days after the second dose were observed among BNT162b2 recipients (1,005 children) and 16 cases were observed among placebo recipients (978 children).
In the group that included all 2,229 participants in the cohort who could be evaluated, regardless of whether they had evidence of previous SARS-CoV-2 infection, no Covid-19 cases were observed among BNT162b2 recipients from seven days after the second vaccine dose and 18 cases were observed among placebo recipients.
After dose 1 and before dose 2, three Covid-19 cases were noted (within 11 days after dose 1) among BNT162b2 recipients, as compared with 12 cases among placebo recipients. No cases of severe Covid-19 were observed in the age cohort studied.
Pfizer had announced on March 25 that the first children in the paediatric trial of the Pfizer-BioNTech Covid vaccine had received their initial vaccine doses. The first doses were given to the cohort aged five to 11 years.
Pfizer said that Phase 1 of the trial was an “open-label, dose-finding study” to identify the preferred dose level(s) of BNT162b2 from up to three different levels (10, 20, and 30 micrograms) with an option for three micrograms, in three age groups (five to 11 years, two to five years, and six months to two years.
The primary endpoints of the study were to evaluate the safety and immunogenicity of the vaccine, Pfizer said. “Vaccine effectiveness in the study will be inferred through immunobridging to the 16- to 25-year-old population from the pivotal Phase 3 trial,” the company added.
Pfizer said that children younger than six months of age might subsequently be evaluated once an “acceptable safety profile” had been established.
On May 28, the European Commission announced that its CMA for the Pfizer-BioNTech vaccine had been expanded to include children aged 12 to 15. This followed a recommendation by the CHMP to authorise use for the 12–15 age group. The extended authorisation is valid in all 27 EU member states. The vaccine had already been approved for use in adults and adolescents aged 16 years and above.
The EC’s decision was also based on data from the Phase 3 trial involving 2,260 children.
Each EU member state can decide whether or not to administer the vaccine to individuals in the 12-15 age group, the EMA said.
The Pfizer-BioNTech vaccine was the first Covid-19 vaccine to receive authorisation in the EU and is the first to have its CMA extended to adolescents.
In Germany, the STIKO has said that only children and adolescents with certain pre-existing conditions should be given the Pfizer-BioNTech vaccine.
The committee said on May 10 that it was only recommending the vaccine for children and adolescents with a condition that raises their risk of a developing a serious case of Covid-19. It cited obesity, immunosuppression, heart defects, chronic lung disease or kidney failure, and diabetes, and children and adolescents with trisomy 21
The STIKO, which is an independent advisory group, also recommends vaccinating children and adolescents who are in close contact with relatives or other people who are at high risk of severe Covid-19 but cannot be vaccinated themselves.
The committee said it was not currently recommending use of the Pfizer-BioNTech vaccine for 12- to 17-year-olds without pre-existing conditions, but advised that the vaccine could be administered after medical advice and with “individual risk acceptance”.
In the UK the JCVI has recommended Covid-19 vaccination for some children and adolescents. The committee said on July 19: “From today, the JCVI is advising that children at increased risk of serious Covid-19 disease are offered the Pfizer-BioNTech vaccine.
“That includes children aged 12 to 15 with severe neurodisabilities, Down’s syndrome, immunosuppression, and multiple or severe learning disabilities.”
The Pfizer-BioNTech vaccine is the only vaccine that has been authorised for children in the UK, for those aged 12 years or older.
The JCVI said it was also recommending that children and young people aged 12 to 17 who live with an immunosuppressed person should be offered the vaccine.
“Under existing advice, young people aged 16 to 17 with underlying health conditions which put them at higher risk of serious Covid-19 should have already been offered vaccination,” the JCVI said.
The committee said that, based on the current evidence, it was not currently advising routine vaccination of children outside of these specified groups.
“As evidence shows that Covid-19 rarely causes severe disease in children without underlying health conditions, at this time the JCVI’s view is that the minimal health benefits of offering universal Covid-19 vaccination to children do not outweigh the potential risks,” the committee said.
The committee has since reiterated this viewpoint, stating on September 3 that, while the health benefits from Covid vaccination for healthy children aged 12 to 15 years were “marginally greater than the potential known harms”, the margin of benefit was considered too small to support universal vaccination of healthy 12- to 15-year-olds at this time.
“Given the very low risk of serious Covid-19 disease in otherwise healthy 12- to 15-year-olds, considerations on the potential harms and benefits of vaccination are very finely balanced and a precautionary approach was agreed,” the JCVI said.
Wei Shen Lim said: “Children aged 12 to 15 years with underlying health conditions that put them at higher risk of severe Covid-19 should be offered Covid-19 vaccination. The range of underlying health conditions that apply has recently been expanded.”
Previously, the JCVI advised that children with severe neurodisabilities, Down syndrome, immunosuppression, profound and multiple learning disabilities, and severe learning disabilities, or who were on the learning disability register, should be offered Covid-19 vaccination.
The committee said that, following consideration of updated data on hospital admissions and deaths, it now advised that 12- to 15-year-olds with the following conditions should also be offered the vaccination:
- haematological malignancy;
- sickle cell disease;
- type 1 diabetes;
- congenital heart disease;
- chronic respiratory disease;
- chronic heart conditions;
- chronic conditions of the kidney, liver, or digestive system;
- chronic neurological disease;
- endocrine disorders;
- asplenia (the absence of a spleen) or dysfunction of the spleen, and
- serious genetic abnormalities that affect a number of systems.
“Children with poorly controlled asthma and less common conditions, often due to congenital or metabolic defects where respiratory infections can result in severe illness, should also be offered Covid-19 vaccination,” the JCVI added.
On September 13, the chief medical officers (CMOs) in the UK’s four nations recommended that the Covid vaccination programme be extended to 12- to 15-year-olds. The UK’s Health Secretary, Sajid Javid, said he accepted the CMOs’ recommendation.
The CMOs said that healthy children should be offered a single dose of the Pfizer-BioNTech vaccine and the rollout should begin as soon as possible.
The CMO for England, Chris Whitty, said that vaccination of 12- to 15-year-olds would “reduce education disruption”. It was for ministers to decide whether to accept the CMOs’ recommendation that Covid vaccination be offered to that age group, he added.
He said the CMOs thought it was “an important and potentially useful additional tool to help reduce the public health impacts that come through educational disruption”.
Pfizer and BioNTech said they were also planning studies to further evaluate their vaccine in people with compromised immune systems.
On July 23, 2021, the TGA in Australia announced that it was extending its provisional approval of the Pfizer-BioNTech vaccine to include children and adolescents aged 12 to 15 years.
The ATAGI recommended that the following groups of children among those aged 12–15 years should be prioritised for vaccination:
- children who are immuno-compromised and those with specified medical conditions that increase their risk of severe Covid-19 (including severe asthma, diabetes, obesity, cardiac and circulatory congenital anomalies, neuro developmental disorders, epilepsy, and trisomy 21 (Down syndrome),
- Aboriginal and Torres Strait Islander children, and
- all children aged 12–15 years in remote communities.
The advisory group said preliminary evidence suggested that children and adolescents had a lower susceptibility to
SARS-CoV-2 compared to adults, and played a lesser role in transmission at a population level.
“Healthy children also have a much lower risk of severe illness from Covid-19 than adults, and typically exhibit a mild course of illness,” the ATAGI said.
“Several publications have reported, however, that children, adolescents and young adults with underlying medical conditions have an increased likelihood of developing severe disease and complications when infected with SARS-CoV-2.”
Only a limited number of studies provided data on these risk associations stratified by selected specific medical conditions, the ATAGI added. Most other published studies reported only by broad disease groups, it said.
On November 10, 2021, the TGA announced that it had granted a provisional determination for Moderna’s Covid vaccine in relation to the proposed use of the vaccine for children aged 6 to 11 years. The vaccine is currently provisionally approved for use for people aged 12 years and above.
“The granting of this determination means that Moderna Australia Pty Ltd is eligible to apply to vary the provisional approval for the vaccine for use in younger children,” the TGA said.
The TGA said Moderna Australia had submitted data for provisional approval and the TGA was assessing use of the company’s vaccine for children aged 6 to 11 years.
Moderna had also submitted an application to the TGA about use of its Covid vaccine as a booster dose and this was under evaluation, the TGA said.
On March 16, 2021, Moderna announced that the first participants in a trial to test its vaccine on children had received their initial doses.
The company stated: “In Part 1, each participant ages two years to less than 12 years may receive one of two dose levels (50 μg or 100 μg). Also in Part 1, each participant ages six months to less than 2 years may receive one of three dose levels (25 μg, 50 μg and 100 μg).
“An interim analysis will be conducted to determine which dose will be used in Part 2, the placebo-controlled expansion portion of the study.
“Participants will be followed through 12 months after the second vaccination. Vaccine effectiveness will either be inferred through achieving a correlate of protection, if established, or through immunobridging to the young adult (ages 18-25) population. Evaluation of vaccine safety and reactogenicity is also a primary endpoint of the study.”
Moderna announced on June 10, 2021, that it had asked the FDA to grant the company an EUA for use of its Covid-19 vaccine for adolescents.
The company said it had also filed for authorisation with Health Canada and would make similar applications to other regulatory agencies around the world.
On May 25, 2021, Moderna issued a statement about its ‘TeenCOVE’ Phase 2/3 study, in which more than 3,700 participants aged 12 to 17 years inclusive were enrolled in the US.
The company said there were no symptomatic cases of Covid-19 among those who received two doses of the vaccine and no significant safety concerns were identified. There were four Covid-19 cases in the placebo group.
Vaccine efficacy of 93% in seronegative participants was observed starting 14 days after the first dose, Moderna said.
“Because the incidence rate of Covid-19 is lower in adolescents, a secondary case definition based on the CDC definition of Covid-19 was also evaluated to include cases presenting with milder symptoms,” the company added.
“Using the CDC definition, which requires only one Covid-19 symptom and a nasopharyngeal swab or saliva sample positive for SARS-CoV-2 by RT-PCR, a vaccine efficacy of 93% after the first dose was observed.”
Moderna said most adverse events were mild or moderate in severity. The most common local adverse event was injection site pain and the most common systemic adverse events after the second vaccine dose were headache, fatigue, myalgia, and chills.
In Britain, a trial in which the AstraZeneca-Oxford vaccine was being tested on children was halted because of the reports of blood clotting in adults who received the vaccine.
A spokesperson from the University of Oxford said: “Whilst there are no safety concerns in the paediatric clinical trial, we await additional information from the MHRA on its review of rare cases of thrombosis/thrombocytopaenia that have been reported in adults before giving any further vaccinations in the trial.
“Parents and children should continue to attend all scheduled visits and can contact the trial sites if they have any questions.”
Children and teenagers aged 6–17 years had been enrolled in the trial, which was set to involve 300 children (up to 150 participants aged 6–11 years and up to 150 aged 12–17 years). Those placed in the control group were being given a meningococcal vaccine, not a saline placebo.
The Oxford researchers argue that, because a saline placebo has no adverse effects, participants who had adverse reactions would know that they had received the AstraZeneca-Oxford vaccine.
“It is critical for this study that participants remain blinded to whether or not they have received the vaccine, as, if they knew, this could affect their health behaviour in the community following vaccination, and may lead to a bias in the results of the study,” the researchers said.
The same vaccine dose was being given as in the trials involving adults. The first doses were given to children aged 12–17 years. Data was to be reviewed before the vaccine was given to younger children.
The researchers said that, because this was the first time the AstraZeneca-Oxford vaccine had been tested on children, only healthy children were being enrolled. “It is likely that, in future studies, children with pre-existing conditions will be enrolled,” they said.
The Oxford researchers said a small number of children had developed serious Covid-19 symptoms and required hospital admission (more than 700 in the first wave in the UK).
“Many of these children had pre-existing medical conditions which made them more susceptible to the effects of a virus which affects the lungs,” the researchers said.
They added that paediatricians have also seen a new inflammatory syndrome emerge, called PIMS-TS, which appears to be associated with Covid-19 disease and often occurs a few weeks after SARS-CoV-2 infection.
The syndrome could make children very unwell and some had suffered multi-organ failure, the researchers said, adding that the number of children affected by the syndrome in the first wave of Covid -19 was fewer than one hundred.
In May 2021, the Ministry of Health and Prevention in the United Arab Emirates (UAE) approved the emergency local use of the Pfizer-BioNTech vaccine for children between the ages of 12 and 15 years.
In November, the ministry approved the emergency local use of the vaccine for children between the ages of five and 11 years.
In India, four Covid vaccines have been approved for use for children and adolescents aged 12 years and above: Covaxin, which is a whole-virion inactivated virus vaccine developed by Bharat Biotech in collaboration with the Indian Council of Medical Research’s National Institute of Virology in Pune; Zydus Cadila’s DNA vaccine ZyCoV-D; Corbevax, a protein subunit vaccine manufactured by Hyderabad-based Biological E. and developed in collaboration with scientists at the Texas Children’s Hospital Center for Vaccine Development and the Baylor College of Medicine in the US; and Covovax, manufactured by the Serum Institute of India (SII). Covovax is the brand name used in India for Nuvaxovid (NVX-CoV2373), originally developed by the American biotechnology company Novavax.
Novavax and the SII announced on March 22 that the Drugs Controller General of India (DCGI) had granted emergency use authorisation for Covovax for 12- to 17-year-olds.
Nuvaxovid/Covovax is a subunit vaccine in which a purified protein is encoded by the genetic sequence of the SARS-CoV-2 spike protein. The gene is inserted into a baculovirus that is then introduced into cells of the fall armyworm moth. The spike proteins are harvested from the moth cells and are assembled into nanoparticles. The vaccine contains a saponin-based adjuvant.
Covaxin was the first Covid vaccine that was been rolled out for children and adolescents in India (initially only for 15- to 18-year-olds). This rollout began in January 2022. The government gave permission for 12- to 14-year-olds to be vaccinated with Corbevax from March 16.
On April 26, Bharat Biotech announced that Covaxin had received emergency use approval for administration to children aged six to 12 years.
The company said the vaccine had been proven to be safe, well-tolerated, and immunogenic in a phase 2/3 study in children aged two to 18 years.
“Neutralising antibodies in children were 1.7 times higher than in adults,” Bharat Biotech said.
India’s union government said it had made its decision about 12- to 14-year-olds “after due deliberations with scientific bodies”.
In an article publised in The Wire Science on March 15, Banjot Kaur reported that these “scientific bodies” did not include the National Technical Advisory Group on Immunisation (NTAGI).
“The NTAGI is one of the bodies whose clearance is required before a vaccine, approved by the drug regulator, can become part of the national COVID-19 vaccination drive,” Banjot Kaur wrote.
Vaccination certificates and restrictions on the unvaccinated
Many countries rapidly introduced regulations that allowed those who had received Covid vaccination access to certain places and facilities and denied such access to those who had not been vaccinated. Entry to numerous countries became dependent on a person’s vaccine status. While most countries have now relaxed their restrictions, some, such as Malaysia, are imposing testing and quarantine only on those who have not been vaccinated. Singapore is still severely restricting the activities of the non-vaccinated in the country.
On May 21, 2022, Israel scrapped all entry regulations at its borders, doing away with PCR testing, proof of vaccination, and quarantine requirements and its ‘green pass’ is no longer required to enter premises.
WHO spokesperson Margaret Harris said on April 6, 2021, that the WHO was saying it would not like to see vaccination passports as a requirement for entry to or exit from countries “because we are not sure at this stage that the vaccine prevents transmission”.
Harris added that vaccine passports might not be an effective strategy as not everyone had access to vaccines and there were groups in society that were excluded.
At its meeting on January 13, 2022, the International Health Regulations (2005) Emergency Committee listed actions it considered to be critical for all countries in relation to the Covid-19 pandemic.
The committee stated that countries should not require proof of vaccination against Covid-19 for international travel “as the only pathway or condition permitting international travel given limited global access and inequitable distribution of Covid-19 vaccines”.
It added that state parties should consider a risk-based approach to the facilitation of international travel “by lifting or modifying measures, such as testing and/or quarantine requirements, when appropriate, in accordance with the WHO guidance”.
International traffic bans should be lifted or eased “as they do not provide added value and continue to contribute to the economic and social stress experienced by States Parties”, the commitee said.
The committee said that the failure of travel restrictions introduced after the detection and reporting of the Omicron variant to limit the international spread of Omicron demonstrated “the ineffectiveness of such measures over time”.
It added: “Travel measures (e.g. masking, testing, isolation/quarantine, and vaccination) should be based on risk assessments and avoid placing the financial burden on international travellers in accordance with Article 40 of the IHR [International Health Regulations].”
There have been demonstrations against vaccine passports and mandates in Canada and the US and in Israel, France, Spain, Austria, Britain, Switzerland, Italy, Ireland, the Netherlands, Portugal, Luxembourg, Greece, Romania, and Croatia. Australia became the focus of international attention because of the harsh crackdown on protests in Melbourne, where hundreds of demonstrators were arrested. The introduction in Australia of mandatory vaccination for construction workers sparked the most recent protests.
Canada’s prime minister, Justin Trudeau, invoked the country’s Emergencies Act to suppress the truckers’ Freedom Convoy blockades.
Trudeau said on February 14, 2022, that the blockades, which had been set up in protest over Covid-19 vaccine mandates and passports, were illegal, and added: “If you’re still participating the time to go home is now.”
The Emergencies Act was passed in 1988, but this is the first time it has been enacted. Trudeau said it would be used to “strengthen and support law enforcement agencies at all levels across the country”.
Once an emergency is declared, the Act goes into effect immediately, but the decision still needs parliamentary approval.
The Act would give police additional tools to “restore order in places where public assemblies could constitute illegal and dangerous activities such as blockades and occupations as seen in Ottawa, the Ambassador Bridge, and elsewhere”, Trudeau said.
The “tools” provided under the Act included strengthening the authorities’ ability to impose fines or imprisonment, he added.
The federal government has also threatened to freeze the personal and corporate bank accounts of protesting truckers and suspend the insurance on their vehicles.
Trudeau’s decision to invoke the Emergencies Act was welcomed by those who are against the blockades, but there has been outrage over his move in many quarters both at home and abroad.
The Canadian Civil Liberties Association said the protests did not meet the standard for invoking the Emergencies Act.
The Emergencies Act can only be invoked when a situation “seriously threatens the ability of the Government of Canada to preserve the sovereignty, security and territorial integrity of Canada” & when the situation “cannot be effectively dealt with under any other law of Canada.”
— Canadian Civil Liberties Association (@cancivlib) February 15, 2022
The premier of Alberta, Jason Kenney, said the Alberta government was opposed to the invocation of the Act. “We have all of the legal tools and operational resources required to maintain order,” Kenney tweeted. “The Act would add no relevant additional powers or resources.”
Speaking on behalf of the Freedom Convoy shortly before Trudeau’s announcement, Tamara Lich said: “First of all, we are not afraid. In fact, every time the government decides to further suspend our civil liberties our resolve strengthens and the importance of our mission becomes clearer.
“We will remain peaceful, but planted on Parliament Hill until the mandates are decisively ended. We recognise that there is a democratic process within which change occurs. We have never stepped outside of that process, nor do we intend to.”
Lich added: “The right to peaceful protest is sacrosanct to our nation. If that principle is abandoned the government will reveal itself as a true tyranny and it will lose all of its credibility.”
The protesting truckers have made the following demands of Canada’s federal and provincial governments:
- that they terminate vaccine passports and all other obligatory vaccine contact-tracing programmes or inter-Canada passport systems;
- that they terminate Covid vaccine mandates and respect the rights of those who wish to remain unvaccinated;
- that they “cease the divisive rhetoric attacking Canadians who disagree with government mandates”; and
- that they “cease to limit debate through coercive measures with the goal of censoring those who have varying or incorrect opinions”.
Austria also came under the spotlight when the government introduced lockdown restrictions specifically for the unvaccinated. It then extended the restrictions to the whole population and there were reports that Covid vaccination would be made mandatory in the country.
In Greece, citizens over the age of 60 were told to book their appointment for a first Covid vaccination by January 16, 2022. Those who failed to comply would be fined €100 a month and would risk jail if they didn’t pay, the government said.
On August 3, 2021, the mayor of New York, Bill de Blasio, announced that access to indoor dining, indoor fitness facilities, and indoor entertainment facilities was to be restricted – in the case of workers and customers – to those who had received at least one dose of a Covid vaccine.
“The only way to patronise these establishments indoors will be if you’re vaccinated; at least one dose,” De Blasio said. “The same for folks in terms of work, they’ll need at least one dose.”
De Blasio said the new policy would be phased in over the following weeks and the final details would be announced and implemented in the week of August 16. Inspection and enforcement would start in the week of September 13. “We’ll be issuing a mayoral executive order and a health commissioner’s order,” De Blasio said.
He said that if people in New York wanted to participate fully in society, they had to get vaccinated.
“ … I want you to imagine the notion that, because someone’s vaccinated, they can do all the amazing things that are available in this city,” De Blasio said.
“This is a miraculous place, literally full of wonders and, if you’re vaccinated, all that’s gonna open up to you. You’ll have the key; you can open the door.
“But if you’re unvaccinated, unfortunately, you will not be able to participate in many things … It’s time for people to see vaccination as literally necessary to living a good and full and healthy life.”
De Blasio argued that the new policy would guarantee a much higher level of vaccination in New York City. “And that is the key to protecting people and the key to our recovery,” he said.
On July 21, 2021, police in Athens used tear gas and water cannons to disperse protesters demonstrating against the Greek government’s plans to make Covid vaccination mandatory for staff in nursing homes and other care facilities.
There was widespread outrage in France over the country’s ‘pass sanitaire’, which showed proof of vaccination, a recent negative SARS-CoV-2 test or past SARS-CoV-2 infection. On January 6, 2022, the French National Assembly approved a bill to transform the ‘health pass’ into a stricter ‘vaccine pass’.
France’s Constitutional Council approved the vaccine pass, which required people aged 16 and above to show proof of vaccination to enter public places like bars, restaurants, and cinemas.
In Montelimar, hospital staff began an indefinite strike in protest against compulsory Covid-19 vaccination.
The vaccine pass was suspended in France from March 14, 2022.
Israel introduced its ‘green pass’ in February 2021. The system expired on June 1, but was later reinstated.
The health ministry announced on August 29 that, as of October 1, 2021, the pass would expire six months after the holder received their second or third Covid vaccine dose.
The ministry also announced that, as of September 3, there would be an exemption from a week-long quarantine for people who had received a third Covid vaccine dose a week earlier if they were returning to Israel from countries considered to have a low or moderate risk of Covid infection.
The exemption also applied to those who had received a second vaccine dose within the previous six months, the ministry said.
The Israeli prime minister, Naftali Bennett, accused those who were eligible to get vaccinated but had not done so of endangering those around them and the freedom of every Israeli citizen. He urged people to persuade others to get vaccinated.
Bennett said people who had been vaccinated would be able to fly to “clean” countries and, on their return to Israel, if their PCR test was negative, they would be exempt from quarantine. The non-vaccinated would have to quarantine for a week, no matter which country they were returning from, and they would have to cover the cost of any PCR tests, he said.
Citizens of the United Arab Emirates who had not received a Covid vaccine booster dose were banned from international travel from January 10, 2022.
The UAE’s Ministry of Foreign Affairs and International Cooperation (MoFAIC) made the announcement in coordination with the National Emergency Crisis and Disasters Management Authority (NCEMA) on January 1.
International travel would only be permitted for unvaccinated citizens in the following categories: those medically exempted from taking the vaccine, “humanitarian cases”, and citizens who are travelling “for medical and treatment purposes”, the ministry said.
Abu Dhabi now requires people entering the city to show proof of booster shots. Visitors are no longer considered fully vaccinated unless they have received a booster at least six months after their second vaccine dose. People wishing to enter Abu Dhabi must also have tested negative for SARS-CoV-2 within the previous two weeks.
IBM developed a Digital Health Pass, using blockchain technology, that stores details about people’s vaccination status and the results of PCR tests.
The pass is designed “to enable organisations to verify health credentials for employees, customers and visitors entering their site based on criteria specified by the organisation”, IBM says.
“Once a vaccine is administered, an individual would be issued a verifiable health credential via the IBM Digital Health Pass that would be included only in that individual’s encrypted digital wallet on their smartphone.”
Iceland was the first country in the Schengen area to issue Covid-19 vaccination certificates, which are given to citizens who have received the full number of vaccine doses.
The country launched an electronic system that enables people to obtain a vaccination certificate online.
“The aim is to facilitate the movement of people between countries so that individuals can present a vaccine certificate at the border and are then exempt from Covid-19 disease control measures in accordance with the rules of the country concerned,” the Ministry of Health said.
Iceland said it would recognise all Covid-19 vaccination certificates issued by EEA/EFTA countries.
On June 1, 2021, the European Commission said the technical gateway for use of the new EU Digital Covid Certificate had gone live, one month ahead of deadline, and seven member states had already started to issue the certificates.
The EC said the system should facilitate free movement inside the EU. “It will not be a pre-condition to free movement, which is a fundamental right in the EU,” the commission said. “Being vaccinated will not be a pre-condition to travel. All EU citizens have a fundamental right to free movement in the EU and this applies regardless of whether they are vaccinated or not.”
The commission added: “Already today, seven member states – Bulgaria, Czechia, Denmark, Germany, Greece, Croatia and Poland – have decided to connect to the gateway and started issuing first EU certificates, while certain countries have decided to launch the EU Digital Covid Certificate only when all functions are deployed nationwide. Therefore, more countries will join in the coming days and weeks.”
Available in digital format or on paper, the certificate records whether people have been vaccinated against Covid-19, recovered from the disease, or recently tested negative for SARS-CoV-2. The Commission proposed that the validity period for tests should be 72 hours for PCR tests and, where accepted by a member state, 48 hours for rapid antigen tests.
The EC said the gateway provided for the verification of the security features contained in the QR codes of all certificates. “This will allow citizens and authorities to be sure that the certificates are authentic. During this process, no personal data is exchanged or retained.”
The commission said the certificate contained necessary key information such as name, date of birth, date of issuance, relevant information about vaccination, test, or recovery from Covid-19, “and a unique identifier”.
It said the data remains on the certificate and is not stored or retained when a certificate is verified in another member state.
“The certificates will only include a limited set of information that is necessary. This cannot be retained by visited countries,” the EC stated. “For verification purposes, only the validity and authenticity of the certificate is checked by verifying who issued and signed it. All health data remains with the member state that issued an EU Digital Covid Certificate.”
On January 27, 2021 the Council of Europe’s parliamentary assembly adopted Resolution 2361, which states that Covid vaccination in EU member states is not mandatory, that no one should be pressured to get themselves vaccinated, and that there should be no discrimination against anyone for not being vaccinated.
Excerpt from the text of Resolution 2361 about Covid-19 vaccines adopted by the Council of Europe’s parliamentary assembly.
The business magnate and self-appointed expert on pandemics Bill Gates (pictured below) wants digital certificates contained in quantum-dot tattoos to be introduced to identify who has been tested for SARS-CoV-2, who has been vaccinated against it, and who has recovered from Covid-19.
Researchers at the Massachusetts Institute of Technology (MIT) have shown that their new dye, which consists of nanocrystals called quantum dots, can remain for at least five years under the skin. The dye emits near-infrared light that can be detected by a specially equipped smartphone.
The dots are only about four nanometres in diameter, but they are encapsulated in microparticles that form spheres about 20 microns in diameter. This encapsulation allows the dye to remain in place, under the skin, after it is delivered by a microneedle patch.
Several airlines, including Etihad Airways, Emirates, Saudia, and Gulf Air trialled a digital travel pass developed by the International Air Transport Association (IATA), which shows whether passengers have been vaccinated and/or have tested negative for SARS-CoV-2.
Writing in the Weekend Australian published on February 7, 2021, Christine Kellett quoted the Minister for Government Services, Stuart Robert, as saying it was “highly likely” that vaccination certificates would be required for international travel.
“There is still a range of decisions for governments to make, it’s highly likely that a certificate will be required for international visitors to Australia and we will continue to work with our international counterparts on our framework for vaccination certificates,” Kellett quoted Robert as saying.
The CEO of the Australian airline Qantas, Alan Joyce, said that proof of Covid vaccination would be compulsory for international air travel on board his aircraft.
The CEO of the International Air Transport Association (IATA), Alexandre de Juniac, said at the time of Joyce’s comment that his stance was a “bit premature” and that testing was more critical than vaccines.
Air New Zealand announced on October 3, 2021, that, from February 1, 2022, it would require customers travelling on its international network to be fully vaccinated, but it has since dropped the requirement.
AirAsia has also dropped its requirement for passengers to be vaccinated.
There is a petition on change.org against mandatory vaccination for international travel, which has been signed by more than 34,000 people.
The UK-based independent tour operator Tradewinds Travel said it would no longer do business with Qantas. “We are not anti-vaccination, but we are pro-choice,” the company said in a statement. “There is a huge difference between coercion and making a free choice.”
The British cruise firm Saga said it would not accept any guest who had not received a Covid vaccination.
“We have taken the decision to introduce the requirement that all guests must be fully vaccinated,” Saga stated on its website. “This means that guests must have received their full two doses of the Covid‑19 vaccination at least 14 days before travelling with us.”
Cruise passengers would be required to bring evidence of vaccination with them at the time of boarding, Saga said. No one who was exempt from vaccination would be accepted on a Saga cruise.
Authorisations in the US, Britain, and Australia
The mRNA-1273 vaccine manufactured by the American company Moderna, and the single-dose Covid vaccine developed by the Johnson & Johnson subsidiary Janssen Biotech are being administered under emergency use authorisations granted by the FDA.
On August 23, 2021, the FDA approved the Biologics Licence Application (BLA) submitted by the German biotech firm BioNTech for the mRNA BNT162b2 vaccine. This was the first approval of a BLA for a Covid vaccine in the US. The vaccine had earlier only been administered under an emergency use authorisation (EUA).
“The vaccine has been known as the Pfizer-BioNTech Covid-19 Vaccine, and will now be marketed as Comirnaty, for the prevention of Covid-19 disease in individuals 16 years of age and older,” the FDA said.
“The vaccine also continues to be available under emergency use authorisation, including for individuals 12 through 15 years of age and for the administration of a third dose in certain immunocompromised individuals.”
The fact that the EUA is still in force means that there will now be two versions of the vaccine in use: the licensed vaccine, Comirnaty, and the EUA-authorised vaccine that has been administered to date. The licensed vaccine is not yet available. The brand name Comirnaty had not previously been used in the US, but it has been used in Europe and Australia.
In a letter to Pfizer, the FDA’s chief scientist, Denise M. Hinton, said: “The licensed vaccine has the same formulation as the EUA-authorised vaccine and the products can be used interchangeably to provide the vaccination series without presenting any safety or effectiveness concerns.
“The products are legally distinct with certain differences that do not impact safety or effectiveness. ”
Robert Malone, who did ground-breaking work in development of the core mRNA vaccine technologies, tweeted: ” … Along with licensure comes liability for the manufacturer. If one receives a vaccine labelled under the EUA (old stock) – it is under EUA. If you get a vaccine from a bottle labelled COMIRNATY, it is approved and there is liability from the manufacturer.”
All the Covid vaccines being administered under an EUA have a “liability shield”, Malone explains.
The director of the FDA’s Center for Biologics Evaluation and Research, Peter Marks, said: “Our scientific and medical experts conducted an incredibly thorough and thoughtful evaluation of this vaccine. We evaluated scientific data and information included in hundreds of thousands of pages, conducted our own analyses of Comirnaty’s safety and effectiveness, and performed a detailed assessment of the manufacturing processes, including inspections of the manufacturing facilities.”
The FDA said it had reviewed updated data from the clinical trial that supported the EUA and included a longer duration of follow-up in a larger clinical trial population.
“Specifically, in the FDA’s review for approval, the agency analysed effectiveness data from approximately 20,000 vaccine and 20,000 placebo recipients ages 16 and older who did not have evidence of the Covid-19 virus infection within a week of receiving the second dose,” the FDA said.
“The safety of Comirnaty was evaluated in approximately 22,000 people who received the vaccine and 22,000 people who received a placebo 16 years of age and older.”
Based on results from the clinical trial, the vaccine was 91% effective in preventing Covid-19 disease, the FDA said.
The FDA said that more than half of the clinical trial participants were followed up for safety outcomes for at least four months after the second dose and, overall, about 12,000 recipients were followed up for at least six months.
In its approval letter to BioNTech the FDA said: “We did not refer your application to the Vaccines and Related Biological Products Advisory Committee because our review of information submitted in your BLA [Biologics Licence Application], including the clinical study design and trial results, did not raise concerns or controversial issues that would have benefited from an advisory committee discussion.”
Pfizer and BioNTech plan to seek licensure of a third dose of their Covid vaccine for people aged 16 years and above and for administration of the vaccine for children and adolescents aged 12 to 15 years “once the required data out to six months after the second vaccine dose are available”.
Just before the FDA’s approval of the Pfizer-BioNTech vaccine Peter Doshi wrote an opinion piece in which he said there was “no legitimate reason to hurry to grant a licence to a coronavirus vaccine”.
Doshi says the FDA should have demanded adequate, controlled studies with long-term follow-up, and made data publicly available, before granting full approval to any Covid-19 vaccine.
The FDA should be demanding that the companies complete the two-year follow-up, as originally planned, Doshi said. “Even without a placebo group, much can still be learned about safety,” he wrote.
“They should demand adequate, controlled studies using patient outcomes in the now substantial population of people who have recovered from Covid.”
Doshi is critical of the FDA’s decision not to convene its advisory committee to discuss the data ahead of approving the Pfizer-BioNTech vaccine.
“Last August, to address vaccine hesitancy, the agency had “committed to use an advisory committee composed of independent experts to ensure deliberations about authorisation or licensure are transparent for the public,” Doshi wrote.
He said that, prior to the publication on July 28, 2021, of a preprint entitled ‘Six Month Safety and Efficacy of the BNT162b2 mRNA COVID-19 Vaccine’, his view and that of about thirty clinicians, scientists, and patient advocates, was that there were simply too many open questions about all Covid-19 vaccines to support approving any in 2021.
“The preprint has, unfortunately, addressed very few of those open questions, and has raised some new ones,” Doshi wrote. It reported decreased appetite, lethargy, asthenia, malaise, night sweats, and hyperhidrosis as new adverse events attributable to BNT162b2 that were not identified in earlier reports, but provided no data tables showing the frequency of these, or other, adverse events, Doshi added.
“In the preprint, high efficacy against ‘severe Covid-19’ is reported based on all follow-up time (one event in the vaccinated group vs 30 in placebo), but the number of hospital admissions is not reported so we don’t know which, if any, of these patients were ill enough to require hospital treatment.”
On the vaccine preventing death from Covid-19, there was too little data to draw conclusions, Doshi said. The crucial question, however, was whether the waning efficacy seen in the primary endpoint data also applied to the vaccine’s efficacy against severe disease, he added.
“Unfortunately, Pfizer’s new preprint does not report the results in a way that allows for evaluating this question,” Doshi said.
“Here we are, with FDA reportedly on the verge of granting a marketing licence 13 months into the still ongoing, two year pivotal trial, with no reported data past 13 March 2021, unclear efficacy after six months due to unblinding, evidence of waning protection irrespective of the Delta variant, and limited reporting of safety data.”
The Pfizer-BioNTech vaccine was granted a temporary authorisation for emergency use by the MHRA in the UK on December 2, 2020.
On December 30, the MHRA also approved the AstraZeneca-Oxford vaccine, which was co-invented by the University of Oxford and its spin-out company, Vaccitech. The authorisation is for emergency use for individuals aged 18 years and above.
In January 2021, the agency also approved the Moderna vaccine for emergency use for individuals aged 18 years and above. The MHRA recommended administration of the second dose 28 days after the first.
On May 28, the MHRA approved the use in Britain, under a conditional marketing authorisation, of the Janssen Biotech vaccine. The agency said the UK government had secured 20 million doses of the vaccine.
The MHRA said that the vaccine met “the expected standards of safety, quality and effectiveness”. The Commission on Human Medicines (CHM) had reviewed the MHRA’s decision and endorsed it, the agency added.
The MHRA said the CMA was valid only in Britain only and was approved via the European Commission (EC) Decision Reliance Route. This is when the marketing authorisation application made by the company references the decision made by the CHMP. The MHRA reviews the application, taking the EC’s decision into consideration, before making an independent decision about the quality, safety, and effectiveness of the vaccine.
The Janssen Biotech vaccine is authorised in Northern Ireland under the CMA granted by the EMA on March 11, 2021.
On February 3, 2022, the MHRA granted conditional marketing authorisation for Nuvaxovid.
The approval authorises the administration of two doses of Nuvaxovid in people aged 18 years and above.
The CMA is only valid in Britain. Nuvaxovid is authorised in Northern Ireland under an emergency use authorisation granted by the EMA on December 20, 2021.
On April 14, 2022, the MHRA announced that it had approved the use in the UK, under a CMA, of the Valneva Covid-19 vaccine (VLA2001). This was the first approval to be given to the Valneva vaccine, which was developed by a company in France. It is the sixth Covid-19 vaccine to be granted an MHRA authorisation and the first inactivated whole-virus Covid-19 vaccine to be approved by the agency.
The MHRA approved the vaccine for administration to people aged 18 to 50 years, with the first and second doses to be taken at least 28 days apart.
The Ministry of Health and Prevention of the United Arab Emirates and the National Health Regulatory Authority in Bahrain granted EUAs for the Valneva vaccine on May 13, 2022, and February 28, 2022, respectively.
On May 19, Valvena said the EMA had accepted the filing of a marketing authorisation application (MAA) for VLA2001.
“Acceptance of the MAA means VLA2001 is advancing from the rolling review process and beginning the formal review process by the EMA’s Committee for Human Medicinal Products,” the company added.
Valvena said it expected to receive a positive CHMP opinion in June 2022. If the CHMP did give a positive opinion, the EC would review the recommendation and provide a final decision on the MAA, the company added.
“If granted by the EC, the centralised marketing authorisation would be valid in all European Union member states as well as in Iceland, Liechtenstein, and Norway,” Valvena said.
Valvena had announced on May 16, 2022, that it had received a notice from the EC of intent to terminate the advance purchase agreement (APA) for VLA2001.
The company said the APA provided the EC with a right to terminate the agreement if VLA2001 had not received a marketing authorisation from the EMA by April 30, 2022.
“Based on the terms of the APA, Valneva has 30 days from May 13, 2022 to obtain a marketing authorisation or propose an acceptable remediation plan,” Valvena said.
Valvena said on April 25, 2022, that it had received a further list of questions from the EMA’s CHMP. The company said it had submitted its responses on May 2 and believed that those responses adequately addressed the remaining questions.
The European Commission has granted CMAs for the Pfizer-BioNTech, AstraZeneca-Oxford, and Moderna vaccines.
The Therapeutic Goods Administration (TGA) in Australia announced on January 25, 2021, that it had granted provisional approval for the Pfizer-BioNTech vaccine BNT162b2 (Comirnaty) for use for individuals aged 16 and older (it has since provisionally approved the vaccine for children and adolescents aged 12 to 15).
On February 16, it announced that it had also granted provisional approval for use of the AstraZeneca vaccine for individuals 18 years and older. Both approvals are valid for two years.
The TGA said the AstraZeneca vaccine should be given in two separate doses. “TGA’s regulatory approval allows the second dose to be administered from four to 12 weeks after the first,” the administration said.
“The Australian Technical Advisory Group on Immunisation has recommended that the interval between first and second dose is 12 weeks. However if this interval is not possible, for example because of imminent travel, cancer chemotherapy, major elective surgery, a minimum interval of four weeks between doses can be used,” the TGA added.
Both approvals are subject to certain conditions, such as the requirement for the companies to continue providing longer term efficacy and safety information to the TGA from their ongoing clinical trials and post-market assessment.
Both vaccines had been shown to prevent Covid-19, the TGA said, but it was not yet known whether they prevent transmission or asymptomatic disease.
The TGA provisionally approved the Moderna vaccine for use in Australia on August 9. It announced on January 20, 2022, that it had also provisionally approved the Nuvaxovid vaccine. The approval was granted to Biocelect Pty Ltd (on behalf of Novavax Inc.).
The TGA said Nuvaxovid was provisionally approved for administration to people aged 18 years and above and it was recommended that the vaccine be given in two doses administered three weeks apart.
The vaccine was provisionally approved for primary vaccination only, the TGA said. “Studies for use of Nuvaxovid as a booster dose and in paediatric patients are ongoing, so the vaccine does not have regulatory approval for these purposes at this stage,” the administration added.
The TGA added that Novavax and the Australian government had announced an advance purchase agreement for 51 million doses of Nuvaxovid in January 2021.
On June 7, 2022, the VRBPAC voted 21–0, with one abstention, in favour of granting an EUA for the Novavax Covid-19 vaccine for administration to people aged 18 years and above.
On July 13, the FDA issued an emergency use authorisation for the vaccine.
The FDA said the vaccine was assessed in a randomized, blinded, placebo-controlled study conducted in the United States and Mexico.
“The effectiveness of the vaccine was assessed in clinical trial participants 18 years of age and older who did not have evidence of SARS-CoV-2 infection through six days after receiving the second vaccine dose, ” the FDA said.
“Among these participants, approximately 17,200 received the vaccine and approximately 8,300 received saline placebo.”
The FDA said that, overall, the Novavax vaccine was 90.4% effective in preventing mild, moderate or severe Covid-19, with 17 cases 9 occurring in the vaccine group and 79 in the placebo group.
“No cases of moderate or severe Covid-19 were reported in participants who received the vaccine, compared with nine cases of moderate Covid-19 and four cases of severe Covid-19 reported in placebo recipients,” the FDA said.
“In the subset of participants 65 years of age and older, the vaccine was 78.6% effective. The clinical trial was conducted prior to the emergence of Delta and Omicron variants.”
The trade name Nuvaxovid has not yet been approved by the FDA.
In its briefing document for the VRBPAC meeting, the FDA raised the issue of the potential risk of myocarditis and/or pericarditis associated with the administration of NVX-CoV2373.
The FDA stated that “the events of myocarditis/pericarditis are concerning for a causal association with NVX-CoV2373 for the following reasons”:
- five events were reported within two weeks of vaccination,
- only one event had a clearly identified alternative etiology (Covid-19) strongly associated with myocarditis, and other events had only circumstantial evidence of potentially plausible alternative etiologies, and
- four of the events occurred in young men, a subject population known to be at higher risk for mRNA Covid-19 vaccine-associated myocarditis.
“Additionally, identification of multiple potential vaccine-associated cases in a premarket safety database of ~40,000 vaccine recipients raises concern that if causally associated, the risk of myocarditis following NVX-CoV2373 could be higher than reported during post-authorisation use of mRNA Covid-19 vaccines (for which no cases were identified in pre-authorisation evaluation),” the document added.
The FDA’s EUA for Moderna’s mRNA-1273 was issued on December 18, 2020, and allows the vaccine to be distributed in the US and to be given to individuals aged 18 years and older.
On February 27, 2021, the FDA issued an EUA for the Janssen Biotech vaccine. This allows the vaccine to be distributed in the US for use in individuals aged 18 years or above.
The FDA said the safety data supporting the EUA included an analysis of 43,783 participants enrolled in a randomised, placebo-controlled study being conducted in South Africa, Mexico, the US, and several countries in South America.
“The participants, 21,895 of whom received the vaccine and 21,888 of whom received saline placebo, were followed for a median of eight weeks after vaccination,” the FDA said. “The most commonly reported side effects were pain at the injection site, headache, fatigue, muscle aches and nausea. Most of these side effects were mild to moderate in severity and lasted 1–2 days.”
Of 39,321 trial participants, 19,630 received the vaccine and 19,691 received a saline placebo.
“Overall, the vaccine was approximately 67% effective in preventing moderate to severe/critical Covid-19 occurring at least 14 days after vaccination and 66% effective in preventing moderate to severe/critical Covid-19 occurring at least 28 days after vaccination,” the FDA said.
“Additionally, the vaccine was approximately 77% effective in preventing severe/critical Covid-19 occurring at least 14 days after vaccination and 85% effective in preventing severe/critical Covid-19 occurring at least 28 days after vaccination.”
There were 116 cases of Covid-19 in the vaccine group that occurred at least 14 days after vaccination, and 348 cases of COVID-19 in the placebo group during the same time period.
There were 66 cases of Covid-19 in the vaccine group that occurred at least 28 days after vaccination and 193 cases in the placebo group during the same time period. Starting 14 days after vaccination, there were 14 severe/critical cases in the vaccinated group versus sixty in the placebo group. Starting 28 days after vaccination, there were five severe/critical in the vaccine group versus 34 cases in the placebo group.
“At this time, data are not available to determine how long the vaccine will provide protection, nor is there evidence that the vaccine prevents transmission of SARS-CoV-2 from person to person,” the FDA said.
Headlines vaunt progress, but there are concerns about safety
Most of the mainstream media vaunt the progress being made in the vaccination drives and are actively engaged in promoting Covid vaccination.
It’s argued that the benefit of vaccination outweighs the risk of adverse events. Adverse reactions are downplayed, even by those suffering them. However, while many of these reactions are short-lived, others are long-lasting and extremely severe. Social media is awash not only with reports of serious health problems occurring after Covid vaccination but also with stories of post-vaccination deaths. It’s impossible to obtain accurate data about adverse events as there is serious underreporting.
On September 26, 2022, VigiBase listed 4,363,443 reports of adverse events following Covid vaccination, including 21,511 deaths (listed under ‘General disorders and administration site conditions’).
Of the 4,363,443 reports of adverse events after Covid vaccination listed on VigiBase as of September 26, 2022, 273,715 were reports of cardiac disorders, 211,084 were reports of vascular disorders, and 194,836 were reports of blood and lymphatic system disorders.
Reproductive system and breast disorders (extract):
Pregnancy, peurperium (postpartum), and perinatal conditions (extract):
The database of the Centers for Disease Control and Prevention’s Vaccine Adverse Event Reporting System (VAERS) in the US lists 1,417,671 adverse event reports after Covid vaccination. The figure relates to reports up to September 16, 2022. A total 6,469,443 individual-symptom events are listed (many reports include more than one symptom).
VAERS puts the number of reports, in all locations, of death following Covid vaccination at 31,071 as of September 16 (14,528 from US states and territories or a location reported as unknown and 16,543 from foreign locations).
According to VAERS, a total 19,930 deaths followed administration of the Pfizer-BioNTech vaccine, 8,385 followed administration of the Moderna vaccine, and 2,704 followed administration of the Janssen Biotech vaccine. In 186 cases, the name of the vaccine manufacturer was not specified in the report. (There’s a discrepancy between the 31,071 figure and the latter 31,025 total.)
A total 3,837 of the reported deaths occurred on the same day as vaccination, 2,971 occurred the following day, 545 occurred within seven days, and 1,491 occurred within ten to 14 days.
According to Worldometers.info there had been 1,080,836 deaths from Covid-19 in the US as of September 23, 2022.
In its update on September 19, 2022, the CDC said more than 612 million doses of Covid-19 vaccines had been administered in the US up to September 14, 2022, and VAERS had received 16,516 preliminary reports of death (0.0027%) among people who received a Covid-19 vaccine. (The figures given on the CDC website do not include adverse event reports from foreign locations.)
On VAERS, 844,490 reports (up to September 16 and in all locations) relate to adverse events after administration of the Pfizer-BioNTech vaccine (4,043,280 individual-symptom events), 479,062 refer to the Moderna vaccine (2,003,893 individual-symptom events), 94,862 refer to the Janssen Biotech vaccine (424,969 individual-symptom events), and 7,633 relate to an unknown vaccine manufacturer (31,216 individual-symptom events). There’s a discrepancy between the 1,417,671 total and this one (1,426,047).
The total number of reported adverse reactions resulting in permanent disability was put at 58,024. VAERS lists, as of September 16, 41,224 cases after administration of the Pfizer-BioNTech vaccine, 13,835 after administration of the Moderna vaccine, and 3,015 after administration of the Janssen Biotech vaccine. In 226 cases, the vaccine manufacturer was not specified. There’s again a discrepancy in the totals.
As of September 16 VAERS listed 10,658 reports of seizures after Covid vaccination. Some other adverse reactions such as generalised tonic-clonic seizure (1,195), seizure-like phenomena (595), and partial seizures (268), are listed separately.
There were 12,694 reports of a pulmonary embolism and 9,817 reports of thrombosis, with separate listings for specific types of thrombosis, such as deep vein thrombosis (8,318), pulmonary thrombosis (1,044), and cerebral venous sinus thrombosis (900). There were 182,318 reports of people being diagnosed with Covid-19.
There were 8,535 reports of a cerebrovascular accident, 11,542 reports of sleep disorders, 13,263 reports of herpes zoster (plus 1,573 other herpes zoster reports listed separately, including herpes zoster reactivation), 2,197 reports of blindness, and 3,199 reports of deafness. As of September 16 there were 22,923 reports of tinnitus.
Miscarriages, stillbirths, and menstrual disorders
As of September 16 VAERS listed 10,658 reports of seizures after Covid vaccination. Some other adverse reactions such as generalised tonic-clonic seizure (1,195), seizure-like phenomena (595), and partial seizures (268), are listed separately.
There were 12,694 reports of a pulmonary embolism and 9,817 reports of thrombosis, with separate listings for specific types of thrombosis, such as deep vein thrombosis (8,318), pulmonary thrombosis (1,044), and cerebral venous sinus thrombosis (900). There were 182,318 reports of people being diagnosed with Covid-19.
There were 8,535 reports of a cerebrovascular accident, 11,542 reports of sleep disorders, 13,263 reports of herpes zoster (plus 1,573 other herpes zoster reports listed separately, including herpes zoster reactivation), 2,197 reports of blindness, and 3,199 reports of deafness. As of September 16 there were 22,923 reports of tinnitus.
The National Institutes of Health (NIH) in the US has awarded one-year supplemental grants totalling $1.67 million to five institutions to explore potential links between Covid-19 vaccination and menstrual changes. One project will focus specifically on adolescents.
“Some women have reported experiencing irregular or missing menstrual periods, bleeding that is heavier than usual, and other menstrual changes after receiving Covid-19 vaccines,” the NIH said.
“The new awards support research to determine whether such changes may be linked to Covid-19 vaccination itself and how long the changes last. Researchers also will seek to clarify the mechanisms underlying potential vaccine-related menstrual changes.”
Immune responses to a Covid-19 vaccine could affect the interplay between immune cells and signals in the uterus, leading to temporary changes in the menstrual cycle, the NIH added. “Other factors that may cause menstrual changes include pandemic-related stress, lifestyle changes related to the pandemic, and infection with SARS-CoV-2,” it said.
Researchers will assess the prevalence and severity of post-vaccination changes to menstrual characteristics including flow, cycle length, pain and other symptoms. “These analyses will account for other factors that can affect menstruation – such as stress, medications and exercise – to determine whether the changes are attributable to vaccination,” the NIH said.
“Several projects also seek to unravel the mechanisms underlying the potential effects of Covid-19 vaccines on the menstrual cycle by examining immune and hormonal characteristics in blood, tissue and saliva samples taken before and after Covid-19 vaccination. “
Researchers in the US who published their findings in the journal Science Advances on July 15, 2022, found that 42% of survey respondents who previously had regular menstrual cycles said they bled more heavily than usual after Covid vaccination.
The researchers conducted a web-based survey of 39,129 people who were currently menstruating or had formerly menstruated and were aged between 18 and 80 years.
“In this sample, 42% of people with regular menstrual cycles bled more heavily than usual, while 44% reported no change after being vaccinated,” the researchers reported.
“Among respondents who typically do not menstruate, 71% of people on long-acting reversible contraceptives, 39% of people on gender-affirming hormones, and 66% of postmenopausal people reported breakthrough bleeding.”
The researchers said they found that increased/breakthrough bleeding was significantly associated with age, systemic vaccine side effects (fever and/or fatigue), history of pregnancy or giving birth, and ethnicity.
“Generally, changes to menstrual bleeding are not uncommon or dangerous, yet attention to these experiences is necessary to build trust in medicine,” the scientists said.
All the survey participants were fully vaccinated (at least 14 days after one or two required doses as the survey was carried out before boosters were administered) and had not contracted Covid-19 (diagnosed or suspected).
The respondents had received either the Pfizer-BioNTech vaccine (21,620 respondents), the Moderna vaccine, (13,001 respondents), the AstraZeneca-Oxford vaccine (751 respondents), the Janssen vaccine (3,469 respondents), Nuvaxovid (61 respondents), or other vaccines (204 respondents). Twenty-three respondents didn’t report the brand of vaccine they received.
Respondents reported noticing changes to their period between one and seven days after vaccination, eight to 14 days after vaccination, or more than 14 days after vaccination. Some respondents reported that they were menstruating when they received the vaccine.
“In total, 42.1% reported heavier menstrual flow after vaccines, 14.3% reported not heavier (characterised by a mix of lighter or no change) menstrual flow, and 43.6% reported no change to flow after vaccines,” the researchers said.
The scientists cite a study conducted in Norway during which researchers found increased reports of heavier periods and longer menstrual bleeding after Covid vaccination that lasted for two to three months.
They also refer to a study in the US in which researchers found longer menstrual cycle lengths after Covid vaccination, but no effect on bleeding duration.
“The only study published thus far that examined menstrual flow after vaccination had similar findings to ours, specifically that people using hormonal contraceptives were more likely to experience heavier bleeding after vaccination,” the scientists added.
There were 2,968 reports of Guillain-Barré syndrome (GBS) listed on VAERS as of September 16, 2022, and 6,745 cases included in the reports of adverse reactions after Covid vaccination on VigiBase as of September 26.
GBS is a rare immune disorder that causes nerve inflammation and can result in pain, numbness, muscle weakness and difficulty walking. It can occur after an infection or the administration of other vaccines, including influenza vaccines.
The CDC said in the update to its website on April 12 that, as of April 7, 2022, about 313 preliminary reports of GBS had been identified on VAERS after administration of the Janssen-Biotech Covid vaccine. As of April 7, more than 18.6 million does of the vaccine had been administered in the US, the CDC added.
The cases had largely been reported about two weeks after vaccination and mostly in men, many aged 50 years and older, the CDC said in April.
The agency is no longer updating the GBS data in the ‘Selected Adverse Events Reported after Covid-19 Vaccination’ section of its website.
“Based on a recent analysis of data from the Vaccine Safety Datalink, the rate of GBS within the first 21 days following J&J/Janssen COVID-19 vaccination was found to be 21 times higher than after Pfizer-BioNTech or Moderna (mRNA COVID-19 vaccines),” the CDC said in its August 23 update. “After the first 42 days, the rate of GBS was 11 times higher following J&J/Janssen Covid-19 vaccination. Analysis found no increased risk of GBS after Pfizer-BioNTech or Moderna (mRNA Covid-19 vaccines).”
Researchers in Britain have identified a link between a first dose of the AstraZeneca Covid-19 vaccine and a rise in cases of Guillain-Barré syndrome.
The scientists conducted a population-based study of National Health Service data in England and also examined surveillance data from UK hospitals. They published their findings in the journal Brain.
They said the data they analysed suggested “a clear and plausible excess of GBS cases” occurring within 42 days after administration of a first dose the AstraZeneca Covid-19 vaccine.
The researchers found that 996 cases of GBS were recorded in the national immunoglobulin database from January to October 2021.
“A spike of GBS cases above the 2016–2020 average occurred in March–April 2021,” Michael P. Lunn et al. reported.
The researchers report that 198 GBS cases occurred within six weeks of the first-dose Covid-19 vaccination in England (0.618 cases per 100,000 vaccinations) and 176 of these cases occurred after administration of the AstraZeneca vaccine.
Twenty-one of the cases occurred after administration of the Pfizer-BioNTech (tozinameran) vaccine and one occurred after administration of the Moderna vaccine.
“The 6-week excess of GBS (compared to the baseline rate of GBS cases 6–12 weeks after vaccination) occurs with a peak at 24 days post-vaccination,” Lunn et al. reported. “First-doses of ChAdOx1 nCoV-19 [the AstraZeneca vaccine] accounted for the excess.”
Twenty-three GBS cases were reported within six weeks of any second Covid-19 vaccine dose.
The researchers said their data gave an estimate of 5.8 excess GBS cases per million first doses of the AstraZeneca vaccine and no measurable excess of GBS associated with first doses of the Pfizer-BioNTech vaccine.
“The absolute number of excess GBS cases from January–July 2021 was between 98–140 cases for first-dose ChAdOx1 nCoV-19 vaccination,” Lunn et al. reported. “First-dose tozinameran and second dose of any vaccination showed no excess GBS risk.”
The researchers said that detailed clinical data from 121 GBS patients were reported in the separate multicentre surveillance dataset during the same timeframe and no phenotypic or demographic differences were identified between vaccine-associated cases of GBS and those that were not associated with vaccination.
“Analysis of the linked NID/NIMS dataset suggests that first-dose ChAdOx1 nCoV-19 vaccination is associated with an excess GBS risk of 0.576 (95% CI 0.481-0.691) cases per 100,000 doses,” Lunn et al. reported.
“However, examination of a multicentre surveillance dataset suggests that no specific clinical features, including facial weakness, are associated with vaccination-related GBS compared to non-vaccinated cases.
“The pathogenic cause of the ChAdOx1 nCoV-19 specific first dose link warrants further study.”
The researchers said the reason for the association between ChAdOx1 nCoV-19 vaccination and GBS was unclear.
“Covid-21 infection does not have a strong, or possibly any, increased risk of GBS, and the lack of increased risk associated with tozinameran vaccination implies that it is unlikely that the Covid-19 spike protein is the causative factor for the increased risk,” Lunn et al. said.
It was logical to suggest that the simian adenovirus vector used in the AstraZeneca vaccine may account for the increased risk, they added.
In a report of the ACIP meeting held on July 22, 2021, the number of reports of GBS after administration of the Janssen Biotech vaccine was put at 100. Ninety-five of the cases were reported to be serious and there was one fatality. The EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) recommended a change to the product information for the AstraZeneca-Oxford vaccine to include a warning “to raise awareness among healthcare professionals and people taking the vaccine of cases of Guillain-Barré syndrome (GBS) reported following vaccination”.
The agency also said in its safety update about the AstraZeneca-Oxford vaccine on September 8 that the product information would be updated to include GBS as a side effect.
The EMA said that, as of July 31, 833 cases of GBS had been reported worldwide after administration of the AstraZeneca-Oxford vaccine. About 592 million doses of the vaccine had been administered worldwide by that date, the agency said.
“Based on the assessment of these data and taking into account neurological expert advice, PRAC concluded that a causal relationship between Vaxzevria and GBS is considered at least a reasonable possibility and that GBS should therefore be added to the product information as a side effect of Vaxzevria,” the EMA said.
The EMA said that the frequency category allocated for GBS was “very rare” (i.e. occurring in less than 1 in 10,000 people). The agency said the PRAC recommended that the existing warning in the package leaflet should be updated with the following advice: “Patients are asked to talk to their healthcare professionals before they are given Vaxzevria if they previously had GBS after being given Vaxzevria”.
The EMA also said in its September 8 update that pain in the legs and arms or stomach and influenza-like symptoms had also been included in the product information as side effects of the AstraZeneca-Oxford vaccine.
On July 12, Johnson & Johnson said that it had updated its Covid-19 vaccine fact sheets to include information (required by the FDA) about cases of GBS and the signs and symptoms of the syndrome. “Updates with this new information will be implemented in other regions of the world according to local regulatory procedures,” the company said.
The company noted that most cases of GBS occurred within 42 days after vaccination. It said that the chance of people developing GBS after administration of the Janssen Biotech vaccine was “very low”.
Fact sheet for recipients and caregivers
Fact sheet for healthcare providers administering the vaccine
The fact sheet for vaccination providers now also also includes thrombosis with thrombocytopenia and capillary leak syndrome in its list of possible severe allergic reactions to the Janssen Biotech vaccine.
A total 507 cases of GBS after administration of the Janssen Biotech vaccine are listed on VAERS up to September 16, 2022.
There were 6,659 reports of Bell’s palsy listed on VAERS as of September 16, 2022, and, as of September 26, there were 10,874 cases listed on VigiBase.
Bell’s palsy, which is also known as acute peripheral facial palsy of unknown cause, is a condition that causes a temporary weakness or paralysis of the muscles in the face. It causes one side of the face to droop or become stiff. In most cases, Bell’s palsy is temporary and symptoms usually start to improve within a few weeks, and there is usually full recovery in about six months. A small number of people continue to have Bell’s palsy symptoms for life. In rare cases, both sides of the face become paralysed.
The FDA said in its briefing document about the Moderna vaccine for the VRBPAC meeting on December 17: “Throughout the safety follow-up period to date, there were three reports of facial paralysis (Bell’s palsy) in the vaccine group and one in the placebo group. Currently available information is insufficient to determine a causal relationship with the vaccine.”
The FDA added: “There were no other notable patterns or numerical imbalances between treatment groups for specific categories of adverse events (including other neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to mRNA-1273.
“There are currently insufficient data to make conclusions about the safety of the vaccine in subpopulations such as children less than 18 years of age, pregnant and lactating individuals, and immunocompromised individuals.”
It added that, of the seven serious adverse events in the mRNA-1273 group that were considered as related by the investigator, the FDA considered three to be vaccine related: intractable nausea and vomiting (one participant), and facial swelling (two participants).
“For the serious adverse events of rheumatoid arthritis, peripheral edema/dyspnea with exertion, and autonomic dysfunction, a possibility of vaccine contribution cannot be excluded,” the FDA said. “For the event of B-cell lymphoma, an alternative etiology is more likely. An SAE [serious adverse event] of Bell’s palsy occurred in a vaccine recipient, for which a causal relationship to vaccination cannot be concluded at this time.”
The FDA said that the serious adverse events were uncommon (1% in both treatment groups) and “represented medical events that occur in the general population at similar frequency as observed in the study”.
The FDA also reported on four cases of Bell’s palsy that occurred in the vaccine group during the Pfizer-BioNTech trial. No cases occurred in the placebo group. The FDA says it will recommend surveillance for cases of Bell’s palsy among those vaccinated.
According to the FDA, the four cases did not represent a frequency above that expected in the general population. The FDA referred to the cases, which occurred at three, nine, 37, and 48 days after vaccination, as “non-serious adverse events”.
“One case (onset at three days post-vaccination) was reported as resolved with sequelae within three days after onset, and the other three were reported as continuing or resolving as of the November 14, 2020, data cut-off with ongoing durations of 10, 15, and 21 days, respectively,” the FDA states.
“The observed frequency of reported Bell’s palsy in the vaccine group is consistent with the expected background rate in the general population, and there is no clear basis upon which to conclude a causal relationship at this time, but FDA will recommend surveillance for cases of Bell’s palsy with deployment of the vaccine into larger populations.”
12- to 17-year-olds
In a report published on July 30, Anne M. Hause et al. from the CDC’s Covid-19 response team said that, as of July 16, 2021, there had been 9,246 reports to VAERS that related to 12- to 17-year-olds who had received the Pfizer-BioNTech vaccine.
A total 8,383 (90.7%) of these reports related to non-serious adverse events and 863 (9.3%) related to serious adverse reactions, including deaths, Hause et al. said.
Approximately 8.9 million 12- to 17-year-olds in the US had received the Pfizer-BioNTech vaccine as of July 16, Hause et al. said.
Fourteen 12- to 17-year-olds died after receiving the Pfizer-BioNTech vaccine, the researchers said. Four of them were aged 12–15 years and ten were aged 16–17 years.
The cause of death has not been determined in six of the cases. Of the eight other cases, two of the deaths are believed to have been from an intracranial haemorrhage, two from a pulmonary embolism, one from heart failure, and one from hemophagocytic lymphohistiocytosis and disseminated mycobacterium chelonae infection. Two of the deaths were suicides.
“Impressions regarding cause of death did not indicate a pattern suggestive of a causal relationship with vaccination; however, cause of death for some decedents is pending receipt of additional information,” Hause et al. said. “ACIP conducted a risk-benefit assessment based in part on the data presented in this report and continues to recommend the Pfizer-BioNTech Covid-19 vaccine for all persons aged ≥12 years.”
Hause et al. said their report had several limitations. “First, VAERS is a passive surveillance system and is subject to underreporting and reporting biases; however, under EUA, health care providers are required to report all serious events following vaccination,” the researchers wrote.
“Second, medical review of reported deaths following vaccination is dependent on availability of medical records, death certificates, and autopsy reports, which might be unavailable or not available in a timely manner.
“Third, lack of a statistical safety signal in planned monitoring does not preclude a safety concern.”
The flaws in the VAERS and other reporting systems are highlighted at length by those who consider that the systems are of no use and rush to point out that anyone can report an adverse effect without evidence that there is a link with vaccination. Those labelled as “anti-vaxxers” are accused of hyping the adverse-event statistics, making fake reports, and fostering vaccine hesitancy.
While correlation does not equal causation, and reports on VAERS and similar databases needs to be treated with caution, the statistics can be an important warning signal about the risks associated with a particular drug or vaccine, particularly when numerous reports accumulate.
Knowingly filing a false VAERS report is a violation of US federal law, punishable by fine and imprisonment.
The CDC warns: “When evaluating data from VAERS, it is important to note that for any reported event, no cause-and-effect relationship has been established. VAERS receives reports on all potential associations between vaccines and adverse events.
“Therefore, VAERS collects data on any adverse event following vaccination, be it coincidental or truly caused by a vaccine. The report of an adverse event to VAERS is not documentation that vaccine caused the event.”
In the caveats noted on the VAERS website, it is stated: “The strengths of VAERS are that it is national in scope and can quickly provide an early warning of a safety problem with a vaccine.”
It is added, however: “While very important in monitoring vaccine safety, VAERS reports alone cannot be used to determine if a vaccine caused or contributed to an adverse event or illness. The reports may contain information that is incomplete, inaccurate, coincidental, or unverifiable.
“Most reports to VAERS are voluntary, which means they are subject to biases. This creates specific limitations on how the data can be used scientifically. Data from VAERS reports should always be interpreted with these limitations in mind.”
In its post-authorisation analysis, which was released as a result of a Freedom of Information Act (FOIA) request, Pfizer gives a breakdown of the 42,086 reports of suspected adverse reactions to its Covid-19 vaccine that were made up to February 28, 2021, (158,893 individual-symptom events).
Pfizer states that 25,379 of the reports were medically confirmed and 16,707 were “non-medically confirmed”. The reports included 1,223 deaths.
The company states in its analysis: “Due to the large numbers of spontaneous adverse event reports received for the product, the MAH [marketing authorisation holder] has prioritised the processing of serious cases, in order to meet expedited regulatory reporting timelines and ensure these reports are available for signal detection and evaluation activity.”
The reference to the estimated number of doses of the Pfizer-BioNTech vaccine that were shipped worldwide from December 1, 2020, to February 28, 2021, was redacted when the post-authorisation analysis was first released on November 17, 2021.
It is unredacted in the version of the document released on April 1, 2022, in which it is stated: “It is estimated that pproximately 126,212,580 doses of BNT162b2 were shipped worldwide from the receipt of the first temporary authorisation for emergency supply on 01 December 2020 through 28 February 2021.”
The following sentence is also unredacted in the document released on April 1. “To date, Pfizer has onboarded approximately 600 additional fulltime employees (FTEs). More are joining each month with an expected total of more than 1,800 additional resources by the end of June 2021.” In the redacted document released in November 2021, the numbers in the sentence are not visible.
Most of the reports of suspected adverse reactions (34,762) were received from the US (13,739), the UK (13,404), Italy (2,578), Germany (1,913), France (1,506), Portugal (866), and Spain (756). The remaining reports came from 56 other countries.
Pfizer says that the greatest number of adverse events in the overall dataset were in the following categories: general disorders and administration site conditions (51,335 adverse events reported), nervous system disorders (25,957), musculoskeletal and connective tissue disorders (17,283), gastrointestinal disorders (14,096), skin and subcutaneous tissue disorders (8,476), respiratory, thoracic and mediastinal disorders (8,848), infections and infestations (4,610), injury, poisoning and procedural complications (5,590), and investigations (3,693).
The document containing the Pfizer analysis was in the first batch provided to the organisation ‘Public Health and Medical Professional for Transparency Documents’ (PHMPT) after it submitted an FOIA request to the FDA for all of the data within Pfizer’s Covid-19 vaccine biological product file.
PHMPT sued the FDA, which released the first batch of documents after a federal judge ordered that it must comply with the FOIA request.
Lawyer for PHMPT Aaron Siri said in a Substack post that the FDA asked a federal judge to make the public wait until the year 2076 to disclose all of the data and information it relied upon to licence the Pfizer-BioNTech Covid-19 vaccine.
“Literally, a 55-year delay, Siri wrote. “My firm, on behalf of PHMPT, asked that this information be disclosed in 108 days – the same amount of time it took for the FDA to review and license Pfizer’s vaccine.”
Siri said that the court (the US District Court for the Northern District of Texas) ordered the parties to submit briefs in support of their respective positions by December 6.
“The FDA’s brief, incredibly, doubles down. It now effectively asks to have until at least 2096 to produce the Pfizer documents. Not a typo. A total of at least 75 years, Siri said.
“Other than producing an initial ~12,000 pages in around two months, the FDA thereafter only wants to commit to producing 500 pages per month. The FDA also disclosed that it actually has approximately at least 451,000 pages to produce.”
On January 6, district court judge Mark T. Pittman rejected the FDA’s request to produce the request documents at a rate of 500 pages per month.
The judge ordered the agency to produce the “more than 12,000 pages” articulated in its own proposal on or before January 31, 2022, and to produce the remaining documents at a rate of 55,000 pages every thirty days, starting on or before March 1, 2022.
“To the extent the FDA asserts any privilege, exemption, or exclusion as to any responsive record or portion thereof, FDA shall, concurrent with each production required by this Order, produce a redacted version of the record, redacting only those portions as to which privilege, exemption, or exclusion is asserted,” Justice Pitman said.
Siri said in a Substack post: “This is a great win for transparency and removes one of the strangleholds federal ‘health’ authorities have had on the data needed for independent scientists to offer solutions and address serious issues with the current vaccine program – issues which include waning immunity, variants evading vaccine immunity, and, as the CDC has confirmed, that the vaccines do not prevent transmission.”
In an order issued on February 2, Justice Pittman said the FDA must release the Pfizer documents according to the following schedule (on the first business day of each month, not once every thirty days):
- 10,000 pages per month for the first two months (due on or before March 1 and April 1, 2022),
- 80,000 pages per month for the following three months (due on or before May 2, June 1, and July 1, 2022),
- 70,000 pages the next month (due on or before August 1, 2022),
- then 55,000 pages on or before the first business day of each month thereafter.
He added that the FDA could “bank” any processed pages in excess of its monthly quota. For example, if the administration produced 90,000 pages in May 2022 (or 65,000 pages in September 2022), it would bank 10,000 pages.
If, in a subsequent month, the FDA was unable to produce the full amount of pages required, it could apply the banked pages toward its quota for that month, Justice Pittman said.
Pfizer says its safety database contains cases of adverse events reported spontaneously to the company, cases reported by the health authorities, cases published in the medical literature, cases from Pfizer-sponsored marketing programmes and non-interventional studies, and cases of serious adverse events reported from clinical studies regardless of causality assessment.
“The limitations of post-marketing adverse drug event reporting should be considered when interpreting these data,” Pfizer said.
“Reports are submitted voluntarily, and the magnitude of underreporting is unknown.”
There were 1,002 cases of anaphylaxis among 1,833 “potentially relevant” reports, Pfizer said.
Pfizer said that no post-authorisation adverse event reports had been identified as cases of vaccine-associated enhanced disease (VAED), including vaccine-associated enhanced respiratory disease (VAERD).
“An expected rate of VAED is difficult to establish so a meaningful observed/expected analysis cannot be conducted at this point based on available data,” Pfizer said. “The feasibility of conducting such an analysis will be re-evaluated on an ongoing basis as data on the virus grows and the vaccine safety data continues to accrue.”
The search criteria used to identify potential cases of VAED for the analysis included MedDRA preferred terms (PTs) that indicated a lack of effect of the vaccine or were potentially indicative of severe or atypical Covid-19, Pfizer added.
As of February 28, 2021, 138 cases, reporting 317 potentially relevant events, were retrieved, the company said.
Of the 317 relevant events, the most frequently reported events were drug ineffectiveness (135), dyspnoea (53), diarrhoea (30), Covid-19 pneumonia (23), vomiting (20), respiratory failure (eight), and seizure (seven).
Overall, there were 37 people with suspected Covid-19 and 101 with confirmed Covid-19 following one or both doses of the vaccine, Pfizer said, adding that 75 of the 101 cases were severe, resulting in hospitalisation, disability, life-threatening consequences, or death.
“None of the 75 cases could be definitively considered as VAED/VAERD,” Pfizer said. “In this review of subjects with Covid-19 following vaccination, based on the current evidence, VAED/VAERD remains a theoretical risk for the vaccine. Surveillance will continue.”
Pfizer says there were 413 reports of adverse events in women who were pregnant or breastfeeding at the time of vaccination. Eighty-four of the cases were considered to be serious. A total 274 of the cases occurred during pregnancy. There were 25 reported miscarriages. Two neonatal deaths and one intrauterine death were reported.
Pfizer details what it describes as Adverse Events of Special Interest (AESIs). These include the following cardiovascular AESIs:
There is also the following data about facial paralysis:
Pfizer’s analysis also includes data about immune-mediated/autoimmune and musculoskeletal AESIs and thromboembolic events:
The detailed list of AESIs in Appendix 1 (possible adverse events that Pfizer flagged as needing to be tracked and reported) is nine pages long.
Pfizer says in its analysis report that “due to the large numbers of spontaneous adverse event reports received for the product”, the marketing authorisation holder (BioNTech) had prioritised the processing of serious cases, “in order to meet expedited regulatory reporting timelines and ensure these reports are available for signal detection and evaluation activity”.
The company said the increased volume of reports had not impacted case processing for serious reports, and compliance metrics continued to be monitored weekly “with prompt action taken as needed to maintain compliance with expedited reporting obligations”.
Pfizer said that non-serious cases were entered into the safety database no later than four calendar days from receipt.
“Non-serious cases are processed as soon as possible and no later than 90 days from receipt,” the company added.
“Pfizer has also taken multiple actions to help alleviate the large increase of adverse event reports. This includes significant technology enhancements, and process and workflow solutions, as well as increasing the number of data entry and case processing colleagues.”
The following safety concerns were raised:
Pfizer concluded that the review of the available data for the “cumulative post-marketing experience” confirmed a favourable benefit-risk balance for the BNT162b2 vaccine.
Reports about the documents released on March 1 (125 separate downloads) and those released on April 1, May 2, June 1, July 1, August 1, and September 1 are to follow.
myocarditis and pericarditis
There are 15,719 reports of myocarditis (inflammation of the heart muscle) after Covid vaccination listed in the VAERS data up to September 16. VAERS lists 81 reports of viral myocarditis, 16 cases of eosinophilic myocarditis, nine cases of hypersensitivity myocarditis, nine cases of giant cell myocarditis, eight cases of infectious myocarditis, five reports of autoimmune myocarditis, five cases of immune-mediated myocarditis, four cases of septic myocarditis, two cases of mycotic myocarditis, two cases of bacterial myocarditis, two cases of post-infection myocarditis, two cases of coxsackie myocarditis, and one case of chronic myocarditis.
The VAERS data also includes 10,340 reports of pericarditis (inflammation of the tissue surrounding the heart), 468 cases of myopericarditis, 95 cases of pleuropericarditis, 54 cases of viral pericarditis, 34 cases of constrictive pericarditis, 15 cases of infective pericarditis, five cases of purulent pericarditis, three cases of adhesive pericarditis, two cases of bacterial pericarditis, one case of uraemic pericarditis, one case of rheumatic pericarditis, one case of cytomegalovirus pericarditis, one case of lupus pericarditis, and one case of autoimmune pericarditis.
The CDC said in the update to its website on April 12, 2022, that, as of April 7, VAERS had received 2,341 preliminary reports of myocarditis or pericarditis among people aged 30 years and younger who received Covid-19 vaccines.
“Most cases have been reported after receiving Pfizer-BioNTech or Moderna, (mRNA Covid-19 vaccines) particularly in male adolescents and young adults.,” the CDC said.
“Through follow-up, including medical record reviews, CDC and FDA have verified 1,433 reports of myocarditis or pericarditis.”
In an update on April 18, the CDC said that a review of vaccine safety from December 2020 to August 2021 found “a small but increased risk of myocarditis” after mRNA Covid-19 vaccines.
More than 350 million mRNA vaccine doses were given during the study period, the CDC said, and CDC scientists found that rates of myocarditis were highest following the second dose of an mRNA vaccine among males in the following age groups:
The CDC said in its update on September 19: “As of September 15, 2022, there have been 1,026 preliminary reports in VAERS among people younger than age 18 years under review for potential cases of myocarditis and pericarditis.
“Of these, 261 remain under review. Through confirmation of symptoms and diagnostics by provider interview or review of medical records, 674 reports have been verified to meet CDC’s working case definition for myocarditis.”
More than half of the cases reported to VAERS after administration of a second dose of either the Pfizer-BioNTech or Moderna vaccines were in people between the ages of 12 and 24, the CDC said in advance of an ACIP meeting in June 2021. Those age groups accounted for less than 9% of doses administered.
The median age of patients who experienced the inflammation after a second vaccine dose was 24, according to the VAERS data and 79% of the cases were in male patients.
The CDC said its preliminary findings suggested the following:
- the median age of reported patients is younger and the median time to symptom onset is shorter among those who developed symptoms after dose 2 as compared with when the patient received only one vaccine dose;
- there is a predominance of male patients in the younger age groups, especially after dose 2;
- there are more observed reports than expected cases after dose 2 in the 16–24 age group;
- there are more cases after dose 2 than after the first dose (about 16 cases per million after second doses); and
- limited outcome data suggests that most patients (at least 81%) fully recovered.
During the presentations at the June 23 meeting, the co-chair of the CDC’s Covid-19 Vaccine Safety Technical (VaST) Work Group, Grace Lee, said that available data suggested a “likely association of myocarditis plus pericarditis with mRNA vaccination in adolescents and young adults”.
Lee said the clinical presentation of myocarditis cases after vaccination had been distinct, occurring most often within one week after dose two, with chest pain as the most common presentation.
Matthew Oster from the CDC’s Covid-19 Vaccine Task Force said it did appear that mRNA vaccines “may be a new trigger for myocarditis”.
During the meeting a summary was presented of initial surveillance findings after vaccination of 12- to 15-year-olds with the Pfizer-BioNTech vaccine.
Statistics from VAERS were presented.
The deputy director of the Immunisation Safety Office at the CDC, Tom Shimabukuro, noted that, as of June 11, there had been 484 preliminary reports of myocarditis and pericarditis among vaccinated people aged under 30 years.
Of the 484 total cases, 323 met the CDC’s definition of myocarditis and/or pericarditis, Shimabukuro said.
A total 309 of the patients were hospitalised and, at the time the data was analysed, 295 of the patients had been discharged. Nine of the patients remained in hospital, including two who were in intensive care.
Details were also provided of the incidence of myocarditis in Israel after Covid vaccination.
Sara Oliver from the CDC’s National Center for Immunisation and Respiratory Diseases (NCIRD) spoke about what was being recommended if someone developed myocarditis after the first dose of an mRNA Covid vaccine.
She said that, until additional safety data were available, experts recommended that administration of the second dose should be deferred. She said administration of the second dose could be considered in certain circumstances, but experts recommended that patients who chose to receive the second dose of an mRNA Covid vaccine should wait at least until the episode of myocarditis was completely resolved.
She said that people who develop pericarditis after the first dose of a Covid mRNA vaccine “may proceed with administration of the second dose after resolution of pericarditis-related symptoms”. The risk of clinically significant sequelae related to pericarditis was low, she said.
Oliver also said that those with a history of pericarditis prior to Covid vaccination can receive any FDA-authorised Covid vaccine. “People who have a history of myocarditis unrelated to Covid vaccination and who have recovered may receive any FDA-authorised COVID-19 vaccine,” Oliver added.
The CDC says that currently “the benefits still clearly outweigh the risks for Covid-19 vaccination in adolescents and young adults”.
While a group of doctors and nurses issued a statement after the ACIP meeting echoing the CDC’s view and saying they “strongly encourage everyone age 12 and older who are eligible to receive the vaccine under emergency use authorisation to get vaccinated”, other medical professionals condemned the CDC’s recommendations.
Retired cardiac surgeon and immunologist Hooman Noorchashm from Pennsylvania tweeted: “Just because C19 vaccine ‘benefits outweigh the risks, numerically’ DOES NOT mean that @CDCgov @US_FDA should tolerate totally avoidable risks. THIS, is how minority harm is born and sustained!”
He added: “Over 5 myocarditis cases in 100,000 COVID vaccinated young persons is NOT RARE!”
Noorchashm also tweeted the following:
According to ACIP presenter from @CDCgov, up to 26% of kids with myocarditis are COVID-recovered!!@DrWoodcockFDA @CDCDirector @US_FDA Y R U not advising against vaccination of COVID-recovered and immune kids? THIS, is your grave error!@TuckerCarlson @SenRonJohnson @RandPaul.
— Hooman MD PhD (@noorchashm) June 23, 2021
Noorchashm says there should be screening before Covid vaccination, including testing for troponin levels in the blood. He has proposed a #ScreenB4Vaccine algorithm to identify the naturally immune and infected.
“It is highly likely, as some powerful anecdotal cases and observational studies are showing already, that persons previously/recently infected with the virus are more susceptible to vaccine-induced adverse reactions, and immunological damage, including myocarditis,” Noorchashm wrote in an article published on Medium on June 23.
It is a rational clinical prediction, Noorchashm says, that those who develop myocarditis after the second Covid vaccine shot likely have early evidence of heart damage in their blood following the first shot.
“It is reasonable to add a troponin blood screen to the #ScreenB4Vaccine algorithm within 10–14 days after the first shot – and especially in the case of children or adults, who may be concerned about the possibility of myocarditis,” Noorchashm wrote.
“If this test comes back positive, it is clear indication of myocardial injury and warrants skipping the second shot, or delaying it until the troponin value is normalised.”
A doctor and translational researcher (molecular bio, neurooncology) in the US, who uses the Twitter handle @AMcA32449832, tweeted about her analysis of the myocarditis/pericarditis/myopericarditis statistics.
I made this slide about myocarditis, pericarditis, and myopericarditis reports in VAERS following #CovidVaccine. As u see, there r much more in the 17-44 yo group than adolescents, and we have known this since JANUARY! But CDC/FDA won’t acknowledge this. pic.twitter.com/yMyS4nCdtM
— AMM, MD (@AMcA32449832) June 24, 2021
On June 25, the FDA announced revisions to its fact sheets for the Moderna and Pfizer-BioNTech vaccines. The agency said the fact sheet for vaccination providers now includes a warning about myocarditis and pericarditis and the one for vaccine recipients and caregivers includes information about the two conditions.
“The warning in the fact sheets for healthcare providers administering vaccines notes that reports of adverse events suggest increased risks of myocarditis and pericarditis, particularly following the second dose and with onset of symptoms within a few days after vaccination,” the FDA said.
“Additionally, the fact sheets for recipients and caregivers for these vaccines note that vaccine recipients should seek medical attention right away if they have chest pain, shortness of breath, or feelings of having a fast-beating, fluttering, or pounding heart after vaccination.”
In a presentation to the ACIP on August 30, John R. Su from the CDC’s Covid -19 Vaccine Task Force said there had been 2,574 reports of myocarditis with pericarditis (myopericarditis) or pericarditis to VAERS as of August 18 (1,903 cases of myopericarditis and 671 cases of pericarditis).
He presented the following slides:
CDC researcher Hannah Rosenblum said that myocarditis could occur in patients with SARS-CoV-2 infection and at higher rates than in those who received mRNA vaccination. She said that the risk of myocarditis after SARS-CoV-2 infection was six to 34 times higher than after administration of an mRNA vaccine.
Rosenblum compared the outcomes for young adults with myocarditis who had Covid-19 and those who developed the condition after Covid vaccination. In the former case, the mean length of stay in hospital was five days, about 5% of patients required mechanical ventilation, and deaths occurred, Rosenblum said. When young adults developed myocarditis after Covid vaccination, the mean stay in hospital was one to two days, and there were no deaths
In the report published by the CDC on July 30, Hause et al. said 397 (4.3%) of the reports related to 12- to 17-year-olds who had received the Pfizer-BioNTech vaccine were about cases of myocarditis.
A total 609 (70.6%) of the reports of serious events were among males and their median age was 15 years, the researchers said.
“The most commonly reported conditions and diagnostic findings among reports of serious events were chest pain (56.4%), increased troponin levels (41.7%), myocarditis (40.3%), increased c-reactive protein (30.6%), and negative SARS-CoV-2 test results (29.4%).”
Writing about the limitation of their report, Hause et al. said that, while a “statistically significant data mining alert” had not been observed for myocarditis following administration of the Pfizer-BioNTech vaccine, myocarditis had been identified in multiple surveillance systems as an adverse event following the use of mRNA Covid-19 vaccines.
Hause et al. said their study was not designed to identify all cases of myocarditis and only reports that listed the MedDRA term “myocarditis” were included.
They noted that v-safe was a voluntary self-enrolment programme that required children aged under 15 years to be enrolled by a parent or guardian and relied on vaccine administrators to promote it. “Therefore, v-safe data might not be generalisable to the overall vaccinated adolescent population,” Hause et al. said.
Findings by a group of researchers in the US, which were published in the Journal of the American Medical Association (JAMA) on August 4, indicated that myocarditis after Covid vaccination occurred more than had been previously reported.
The CDC had estimated that the incidence was about 0.48 cases per 100,000 vaccine doses, but George Diaz et al. found that it occurred at a rate of one case per 100,000 doses.
They also found that the rate of pericarditis after Covid vaccination was 1.8 cases per 100,000 vaccine doses and, when myocarditis and pericarditis occurred together, the incidence was 2.8 cases per 100,000 vaccine doses.
The higher incidence suggests that there is underreporting of vaccine adverse events, Diaz et al. said. “Additionally, pericarditis may be more common than myocarditis among older patients.”
Diaz et al. reviewed the electronic hospital records of more than two million people who received at least one Covid-19 vaccination. They found 37 cases of vaccine-related pericarditis and 20 cases of vaccine-related myocarditis.
“Myocarditis developed rapidly in younger patients, mostly after the second vaccination,” the researchers said. “Pericarditis affected older patients later, after either the first or second dose.”
Diaz et al. wrote: “Among 2,000,287 individuals receiving at least one Covid-19 vaccination, 58.9% were women, the median age was 57 years … 76.5% received more than one dose, 52.6% received the BNT162b2 vaccine (Pfizer/BioNTech), 44.1% received the mRNA-1273 vaccine (Moderna), and 3.1% received the Ad26.COV2.S vaccine (Janssen/Johnson & Johnson).
“Twenty individuals had vaccine-related myocarditis (1.0 [95% CI, 0.61-1.54] per 100,000) and 37 had pericarditis (1.8 [95% CI, 1.30-2.55] per 100,000).”
Diaz et al. said that myocarditis occurred a median of 3.5 days after vaccination.
Eleven of the cases of myocarditis occurred after administration of the Moderna vaccine and nine occurred after administration of the Pfizer-BioNTech vaccine. Fifteen of those affected were male, and the median age was 36 years.
Four people developed symptoms after the first vaccine dose and 16 developed symptoms after the second. Nineteen patients were admitted to hospital and all were discharged after a median of two days. There were no readmissions or deaths.
Two patients received a second vaccination after the onset of myocarditis and neither had a worsening of symptoms.
At the last available follow-up (median 23.5 days) after symptom onset, 13 patients had symptom resolution and seven were improving, Diaz et al. said.
Pericarditis developed after the first vaccine dose in 15 cases and after the second dose in 22 cases.
Twenty-three of the cases occurred after administration of the Pfizer-BioNTech vaccine,12 occurred after administration of the Moderna vaccine, and two cases occurred after administration of the Janssen Biotech vaccine.
Median onset was twenty days after the most recent vaccination. Twenty-seven of those affected were male and the median age was 59 years.
Thirteen of the patients were admitted to hospital, none to intensive care. The median hospital stay was one day. None of the patients died.
Seven patients with pericarditis received a second vaccination. At the last available follow-up (median 28 days), seven patients had resolved symptoms and 23 were improving.
The mean monthly number of cases of myocarditis or myopericarditis during the pre-vaccine period was 16.9 compared with 27.3 during the vaccine period, Diaz et al. said. The mean numbers of pericarditis cases during the same periods were 49.1 and 78.8 respectively.
Diaz et al. said that the limitations of their study included cases missed in outside care settings and missed diagnoses of myocarditis or pericarditis, which would underestimate the incidence, as well as inaccurate vaccination information in electronic medical records.
“Temporal association does not prove causation, although the short span between vaccination and myocarditis onset and the elevated incidence of myocarditis and pericarditis in the study hospitals lend support to a possible relationship,” the researchers added.
There have been reports of myocarditis after flu vaccination and federal health officials in the US stated in March 2003 that ten military personnel and two civilians developed heart inflammation after smallpox vaccination.
The CDC said the military personnel had mild myocarditis within six to 12 days after receiving a smallpox vaccine and all of them recovered completely. The two civilians also improved or recovered, officials said at the time.
“Data from the military smallpox vaccination programme are consistent with a causal association between vaccination and myopericarditis, although this association is not proven,” the CDC stated.
On September 26, 2022, on Vigibase, there were 25,889 cases of myocarditis, 21,135 cases of pericarditis, and 3,007 cases of myopericarditis included in the reports of adverse reactions after Covid vaccination.
On October 6, Sweden’s Public Health Agency said it was halting use of Moderna’s Covid-19 vaccine for people born in 1991 and later and the Danish Board of Health said it had decided not to administer the vaccine to people aged under 18.
Both authorities said they were acting out of precaution because of reports of adverse effects such as myocarditis and pericarditis.
The Norwegian Institute of Public Health has meanwhile recommended that young people under the age of 18 should be offered the Pfizer-BioNTech vaccine regardless of which mRNA vaccine they received as the first dose.
Deputy director-general at the Norwegian institute Geir Bukholm said that men under the age of thirty should also consider choosing the Pfizer-BioNTech vaccine.
“Monitoring analyses of reported adverse reactions from the United States have suggested that myocarditis may be more frequent when using Moderna’s vaccine as a second dose than the BioNTech-Pfizer vaccine, but the numbers have been small and therefore uncertain,” Bukholm added.
“New monitoring data from Ontario, Canada, substantiates that this observation is correct, and preliminary monitoring data from Norway, Sweden, and other countries could indicate the same.”
The programme manager for Denmark’s childhood vaccination programme, Bolette Søborg, said: “In Denmark, it has so far been the case that children and young people aged 12–17 have primarily been invited to receive the Covid-19 vaccine from Pfizer-BioNTech.
“Based on the precautionary principle, we will in future only invite children and young people to receive this vaccine, not least in light of the fact that it is for this vaccine that the largest amount of data from use exists for children and young people, especially from the USA and Israel.”
Søborg noted that Denmark had not seen an increase in cases of myocarditis.
The Swedish Public Health Agency said it had decided to suspend the use of the Moderna vaccine for people born in 1991 and later, also “for precautionary reasons”.
The agency said it had taken the decision because of signals of an increased risk of adverse effects such as myocarditis and pericarditis.
It pointed to the particular risk for adolescents and young adults, and mainly boys and men, but added that “for the individual, the risk of being affected is very small; it is a very rare side effect”.
It said that, according to new preliminary analyses in Sweden and other Nordic countries, which have not yet been published, the connection was especially clear with the Moderna vaccine, especially after the second dose. “The increase in risk is seen within four weeks after the vaccination, mainly within the first two weeks,” the agency added.
The Danish health agency cited the same data and said that researchers in Denmark, Sweden, Norway, and Finland had investigated the risk of pericarditis and myocarditis after administration of the Pfizer-BioNTech and Moderna Covid vaccines.
“In the preliminary data … there is a suspicion of increased risk of heart inflammation after vaccination with the Moderna vaccine, although the number of cases of heart inflammation remains very low,” the agency said.
The data from the Nordic study have been sent to the EMA’s adverse reaction committee.
The Swedish health agency said it was now recommending the Pfizer-BioNTech vaccine for people born in 1991 and later, and added that its decision was valid until December 1, 2021. It has since extended the halt on the use of Moderna’s Covid-19 vaccine beyond December 1.
“People born in 1991 and later who have received a dose of Moderna’s vaccine will not be offered a second Covid-19 vaccine dose at present,” the agency said. “Discussions are ongoing about the best solution for that group. In total, there are about 81,000 people.”
Sweden’s state epidemiologist, Anders Tegnell, said that those who had recently received a first or second dose of Moderna’s vaccine did not have to worry as the risk was very small. “However, it is good to know what symptoms you need to be vigilant about,” he added.
On October 11, the Finnish Institute for Health and Welfare said that the Moderna Covid vaccine would not be given to males aged under 30 years. The insitute said it had instructed municipalities to offer boys and men aged under 30 years only the Pfizer-BioNTech Covid vaccine.
The institute said that, according to the Nordic study, “the relative occurrence of myocardial inflammation” was higher for Moderna’s vaccines than for the Pfizer-BioNTech vaccine, “and the risk of myocardial inflammation after vaccination is higher in young men than in women”.
The Finnish institute added that its guideline on the age limit for use of the Moderna vaccine was a precautionary measure and would be reviewed in November as the results of the Nordic study became clear.
Chief physician at the institute Hanna Nohynek said: “The results now obtained are still preliminary. We are currently analysing them and assessing whether they give cause for more permanent changes to the recommendations for coronavirus vaccination in Finland.”
The Finnish institute previously issued instructions that third vaccine doses should not be offered to men aged under 30 years as there was still insufficient data on the connection between third doses and the risk of myocardial inflammation.
“An exception is made, however, for strongly immunodeficient persons whose risk of serious coronavirus disease is significantly higher than in other people of the same age,” the institute said.
It said it had also issued instructions that men under 30 years of age with strong immunodeficiency should, for the time being, be offered only the Pfizer-BioNTech vaccine as their third dose.
Iceland has meanwhile suspended the use of the Moderna Covid vaccine, also citing concerns about the increased risks of cardiac inflammation.
Iceland’s health directorate said that, as there was a sufficient supply of the Pfizer-BioNTech vaccine in the country, the chief epidemiologist had decided that the Moderna vaccine should not be used.
The directorate said that, over the past two months, the Moderna vaccine had been used almost exclusively for booster doses after administration of the Janssen vaccine and after two-dose vaccinations for the elderly and immunocompromised. Very few people had received the second dose of primary vaccination with the Moderna vaccine.
In Canada, the province of Ontario now recommends that people aged 24 years and under should receive the Pfizer-BioNTech vaccine in preference to the Moderna vaccine. The Canadian National Advisory Committee on Immunisation continues to recommend vaccination with either mRNA vaccine for people aged 12 years and over.
The Central News Agency in Taiwan and the Taiwan News reported on November 10, 2021, that a panel of experts had decided to suspend administering second doses of the Pfizer-BioNTech Covid vaccine to 12- to 17-year-olds amid concerns about an increased risk of myocarditis.
The news outlets said the Ministry of Health and Welfare’s Advisory Committee for Immunisation Practices had decided to halt administration of second Pfizer-BioNTech doses for the age group for two weeks while experts, including physicians from Taiwan’s Centres for Disease Control, investigated the 16 cases of myocarditis that had occurred among adolescents in Taiwan after administration of the Pfizer-BioNTech vaccine.
A decision would then be made about whether or not the second dose should be administered to 12- to 17-year-olds, the news outlets reported, quoting the head of Taiwan’s Central Epidemic Command Centre, Chen Shih-chung.
On July 9, 2021, the EMA said the PRAC had concluded that myocarditis and pericarditis could occur “in very rare cases” following vaccination with the Pfizer-BioNTech and Moderna vaccines.
“The committee is therefore recommending listing myocarditis and pericarditis as new side effects in the product information for these vaccines, together with a warning to raise awareness among healthcare professionals and people taking these vaccines,” the EMA said.
The EMA said the PRAC had reviewed reports in the EEA of 145 cases of myocarditis and 138 cases of pericarditis after administration of the Pfizer-BioNTech vaccine and 19 cases of myocarditis and 19 cases of pericarditis after administration of the Moderna vaccine.
The agency added: “The committee concluded that the cases primarily occurred within 14 days after vaccination, more often after the second dose and in younger adult men.
“In five cases that occurred in the EEA, people died. They were either of advanced age or had concomitant diseases. Available data suggest that the course of myocarditis and pericarditis following vaccination is similar to the typical course of these conditions, usually improving with rest or treatment.”
The EMA said that, “at this point in time”, no causal relationship with myocarditis or pericarditis could be established with the AstraZeneca-Oxford or Janssen vaccines. “The committee has requested additional data from the companies marketing these vaccines,” the agency added. The EMA says that the benefits of all authorised Covid-19 vaccines continue to outweigh their risks.
On August 3, 2022, the PRAC issued a warning about a “possible link to myocarditis and pericarditis with Nuvaxovid”.
“The PRAC has concluded that myocarditis and pericarditis can occur following vaccination with Nuvaxovid,” the committee said. “This conclusion is based on a small number of reported cases.”
The committee recommended listing myocarditis and pericarditis “as new side effects in the product information for Nuvaxovid, together with a warning to raise awareness among healthcare professionals and people receiving this vaccine”.
In April, media in Israel said the country’s health ministry was investigating more than sixty cases of myocarditis after administration of the Pfizer-BioNTech vaccine.
Local media said an unpublished report from the ministry stated that there had been 62 cases of myocarditis reported after administration of the vaccine. Fifty-six of the cases occurred after administration of the second dose and most of the people affected were men aged under 30 years, media reports added.
According to Channel 12, sixty of the patients recovered and were discharged from hospital, but two of them (a woman aged 22 years and a man aged 35) died.
The Times of Israel reported on June 2 that Israel’s health ministry has concluded that there was a probable link between the second dose of the Pfizer-BioNTech vaccine and dozens of cases of myocarditis in males aged under 30 years.
One of the patients who developed myocarditis after receiving the Pfizer-BioNTech vaccine died, The Times of Israel reported, but the ministry said a link between the vaccination and the person’s death had not been conclusively proven.
The ministry says that, from December 2020 to May 2021, there were 275 cases of myocarditis reported across Israel, 148 of which occurred shortly after the patient was vaccinated.
According to The Times of Israel, 27 cases, including 11 people with pre-existing conditions, were reported shortly after the first vaccine dose, which had been received by 5,401,150 people in total.
There were 121 cases reported as occurring within 30 days of the second vaccine dose (among 5,049,424 people who received that dose). Sixty of those patients are reported to have had pre-existing conditions.
The health ministry said the vast majority of those affected were men aged under 30, particularly those between the ages of 16 and 19 years. Most of the cases were mild, the ministry added, and patients were released from the hospital after four days.
On January 24, 2021, The Jerusalem Post reported on the case of a 17-year-old youth, reported to have no pre-existing illnesses, who was hospitalised after receiving his second Covid vaccine dose.
The youth was admitted to an intensive care unit after feeling intense pains in his chest, the Post reported. The teenager was reported to be in a stable condition.
The Post reported on February 1, 2021, that the teenager developed myocarditis five days after receiving his second vaccine dose of a Covid vaccine.
“According to the clinic, it has still not been confirmed that the inflammation was developed as a side effect of the vaccination. However, a number of Covid-19-related myocarditis cases have been reported, according to the US National Institutes of Health,” Maayan Jaffe-Hoffman reported.
Arutz Sheva reported in January on the case of a a 23-year-old man who developed a rare inflammatory syndrome 24 hours after receiving the Pfizer-BioNTech Covid vaccine.
The director of the coronavirus department at the Hadassah Medical Centre, Professor Dror Mevorach, tweeted on January 9 about the case.
Rare life-threatening multi-system inflammatory syndrome (MIS) following BNT162b2 mRNA covid-19 vaccination in a 23 y old social worker was identified at our Department of Medicine B at Hadassah Medical Center, Jerusalem, Israel and reported to MOH and WHO. >>
— Dror Mevorach (@DrorMevorach) January 9, 2021
Mevorach told Channel 12: “We found out that the young man had contracted the coronavirus asymptomatically before he was vaccinated. It may be accidental, but I would not underestimate it. Care must be taken in vaccination of people who were sick with coronavirus in the past.”
Data from Europe
EudraVigilance lists 2,068,238 adverse reaction cases that relate to the five vaccines authorised for use in Europe.
The database lists 1,128,289 individual cases up to September 24, 2022, for the Pfizer-BioNTech vaccine (tozinameran). Most are from Germany (206,598), followed by the Netherlands (125,856), and France (121,976).
A total 527,326 cases are listed for the AstraZeneca-Oxford vaccine up to September 24 with the most listed in Germany (53,914), followed by Austria (41,244), and the Netherlands (38,332).
A total 341,817 cases are listed for the Moderna vaccine. Most are from Germany (62,603), followed by the Netherlands (49,758), and France with 31,999.
A total 69,435 cases are listed for the Janssen Biotech vaccine. Most are from the Netherlands (15,266), followed by Germany with 11,735, and Austria (11,187).
A total 1,371 cases are listed for the Novavax vaccine. Most are from Germany (923), followed by Italy with 150 cases, and France with 87.
In its report about suspected cases of adverse events and vaccination complications from the start of Covid-19 vaccination in Germany on December 27, 2020 to March 31, 2022, the Paul-Ehrlich-Institut says it received 296,233 reports of suspected adverse events.
“The overall reporting rate for all vaccines was 1.7 reports per 1,000 doses of vaccine,” the institute said, adding that the reporting rate for serious adverse events in Germany was 0.2 reports per 1,000 doses of vaccine.
The institute says 172,062,925 Covid-19 vaccinations were administered in Germany between December 27, 2020 and March 31, 2022. A total 73.3% of the vaccine doses were Comirnaty, 17.1% were Moderna, 7.4% were AstraZeneca, 2.1% were Janssen, and 0.1% were Nuvaxovid.
“In about one percent of the suspected case reports (n = 2,810 cases), death was reported at varying time intervals to Covid-19 vaccination,” the institute said. “116 cases were assessed by the Paul-Ehrlich-Institut to be consistent with a causal link to the respective Covid-19 vaccination (probable or possible causal relationship).”
On January 14, 2022, the PRAC said it had recommended a change to the product information for Vaxzevria and the Janssen Biotech vaccine to include a warning about the spinal inflammatory disorder transverse myelitis (TM) reported following administration of the vaccines.
TM had also been added as an adverse reaction of unknown frequency, the EMA said.
“TM is a rare neurological condition characterised by an inflammation of one or both sides of the spinal cord,” the EMA added. “It can cause weakness in the arms or legs, sensory symptoms (such as tingling, numbness, pain or loss of pain sensation) or problems with bladder or bowel function.”
The EMA said the PRAC had reviewed available information on globally reported cases, including those in EudraVigilance and data from the scientific literature, after the administration of Vaxzevria and the Janssen Biotech vaccine.
Thirty-eight globally reported cases were considered (25 after administration of Vaxzevria and 13 after administration of the Janssen Biotech vaccine).
“Respectively, global exposure to the vaccines was estimated at 1,391 billion doses for Vaxzevria and at 33,584,049 for Covid-19 Vaccine Janssen,” the EMA said. “These numbers refer to suspected and not adjudicated cases of TM.
“The PRAC has concluded that a causal relationship between these two vaccines and transverse myelitis is at least a reasonable possibility. The benefit-risk profile of both vaccines remains unchanged.”
The EMA said healthcare professionals should be alert to signs and symptoms of TM, “allowing early diagnosis, supportive care and treatment”.
The PRAC also recommended updating the product information for Vaxzevria to add more information about thrombosis with thrombocytopenia occurring after vaccination.
“A review of cumulative data has highlighted that the majority of suspected TTS events were reported worldwide after the administration of the first dose,” the EMA said. “Fewer events have been observed after the second dose.”
The EMA said that, of the 1,809 thromboembolic events with thrombocytopenia reported worldwide, 1,643 were reported after the first dose and 166 after the second dose.
“As per the current product information, the administration of a second dose of Vaxzevria is contraindicated in people who have experienced TTS following vaccination with this vaccine,” the agency added.
The EMA said on August 11, 2021, that the PRAC was investigating three reported conditions to see if they are adverse reactions to the Moderna and Pfizer-BioNTech vaccines. The conditions being assessed were erythema multiforme, glomerulonephritis, and nephrotic syndrome.
Erythema multiforme is a hypersensitivity (allergic) reaction that is characterised by round skin lesions and can also affect mucous membranes in internal body cavities.
Glomerulonephritis is an inflammation of tiny filters in the kidneys and nephrotic syndrome is a disorder that causes the kidneys to leak too much protein in the urine.
The assessments relating to erythema multiforme followed the reporting to EudraVigilance of a small number of cases after vaccination with the Moderna and Pfizer-BioNTech vaccines, the EMA said.
“Reported cases concern suspected side effects, i.e. medical events that have been observed after vaccination, but which are not necessarily related to or caused by the vaccine,” the EMA said.
Further data and analyses had been requested from the marketing authorisation holders to support the ongoing assessment by PRAC, the agency added.
The EMA said the PRAC had also started an assessment of glomerulonephritis and nephrotic syndrome to establish whether they may be side effects of the Moderna and Pfizer-BioNTech vaccines.
“Affected patients may present with bloody or foamy urine, oedema (swelling of the eyelids, feet or abdomen), or fatigue,” the EMA said.
The assessments followed a small number of cases reported after vaccination with the Moderna and Pfizer-BioNTech vaccines, the agency added. These cases were reported in the medical literature and included cases where patients experienced a relapse of pre-existing kidney conditions.
Again, further data and analyses had been requested from the marketing authorisation holders to support the ongoing assessments by the PRAC, the EMA said.
The EMA said that, as of July 29, 48,788 cases of suspected side effects after administration of the Moderna vaccine were reported to EudraVigilance from the EU and the additional countries of the EEA. In 392 of these cases, there was a fatal outcome, the agency said.
By the same date, about 43.5 million doses of the Moderna vaccine had been administered in the EU and the additional countries of the EEA, the EMA said.
The EMA said that, as of July 29, 244,807 cases of suspected side effects after administration of the Pfizer-BioNTech vaccine were reported to EudraVigilance from the EU and the additional countries of the EEA. In 4,198 of these cases, there was a fatal outcome, the agency said.
By the same date, about 330 million doses of the Pfizer-BioNTech vaccine had been administered in the EU and the additional countries of the EEA, the EMA said.
Data from the UK
The MHRA published a new summary of yellow card reporting on September 1. A full report about this data will be published shortly on Changing Times.
In its summary of Yellow Card reporting, published on August 4, 2022, the MHRA said that, as of July 27, it had received and analysed 460,533 reports of suspected adverse reactions after Covid vaccination.
A total 245,996 reports related to the AstraZeneca Covid-19 vaccine. The total number of listed adverse reactions is 871,710 (a single report may contain more than one symptom). The first report was received on January 4, 2021, the day the vaccine was first administered in the UK.
As of July 27, 172,476 reports of adverse reactions had been submitted relating to vaccination with the Pfizer-BioNTech vaccine. These include a total of 497,104 suspected reactions. The first report was received on December 9, 2020, the day after the vaccine was first administered in the UK.
A total 40,270 Yellow Card reports related to the Moderna vaccine. These include a total of 133,392 suspected reactions. The first report was received on April 7.
There were 1,791 reports of adverse reactions in which the brand of the vaccine was not specified (5,471total suspected reactions).
The MHRA has received 2,191 UK reports of people dying shortly after Covid vaccination. There were 1,297 reports of death after administration of the AstraZeneca Covid-19 vaccine, 815 after vaccination with the Pfizer-BioNTech vaccine, and 65 after administration of the Moderna vaccine. Forty-nine deaths were reported in cases in which the vaccine brand was unspecified.
“As the number of vaccine doses administered has increased, so has the number of reports with fatal outcomes following vaccination,” the MHRA said. “However, this does not mean that there is a link between vaccination and the fatalities reported.”
According to Worldometers.info, 186,087 people were reported to have died from Covid-19 in the UK as of August 15, 2022.
The MHRA said that, in the 14 days since the previous summary to July 13, it had received a further 258 Yellow Card reports relating to administration of the Pfizer-BioNTech vaccine, 202 reports after administration of the Moderna vaccine, 93 reports after administration of the AstraZeneca Covid-19 vaccine, and 12 reports in which the vaccine brand was not specified.
“It is important to note that Yellow Card data cannot be used to derive side-effect rates or compare the safety profile of Covid-19 vaccines as many factors can influence ADR [adverse reaction] reporting,” the agency said.
The MHRA said that data from the UK public health agencies showed that at least 53,704,436 people had received their first vaccination in the UK by July 26,2022, and 50,470,230 second doses had been administered.
As of July 26, an estimated 27.1 million first doses of the Pfizer-BioNTech vaccine and 24.9 million first doses of the AstraZeneca Covid-19 vaccine had been administered, plus about 24.7 million and 24.1 million second doses of the Pfizer-BioNTech and AstraZeneca Covid-19 vaccines respectively.
About 1.7 million first doses and 1.6 million second doses of the Moderna vaccine have also been administered.
As of July 26, an estimated 40,186,381 people had received their booster or additional vaccination in the UK, the MHRA said.
An estimated 30.7 million third or booster doses of the Pfizer-BioNTech vaccine, 58,300 third or booster doses of the AstraZeneca Covid-19 vaccine, and 9.4 million third or booster doses of the Moderna Covid vaccine had been administered, the agency added.
The MHRA said that, as of July 27, it had received 31,983 UK reports of suspected adverse reactions after the reported administration of a booster dose of the Pfizer-BioNTech vaccine.
The agency added that it had received 18,369 reports of suspected adverse reactions after the reported administration of a Moderna booster dose, 599 such reports after the reported administration of a booster dose of the AstraZeneca Covid-19 vaccine, and 213 such reports in which the brand of the booster dose was not specified.
In the case of the Pfizer-BioNTech vaccine this represented a reporting rate of one report per 1,000 third or booster doses and for the Moderna vaccine there were an estimated two reports per 1,000 third or booster doses, the MHRA said.
Both of these rates were lower than the reporting rate for all Covid-19 vaccine doses combined, which was between two and five reports per 1,000 doses, the agency added.
In the case of the Covid-19 Vaccine AstraZeneca a very limited number of booster doses had been administered in the UK and there had been a very small number of reports of adverse reactions, the MHRA said.
“There is insufficient experience with Covid-19 Vaccine AstraZeneca as a booster vaccine to be able to make similar estimates of reporting rates,” the agency added.
“The nature of events reported with third and booster doses is similar to that reported for the first two doses of the Covid-19 vaccines, and the vast majority of reports relate to expected reactogenicity events.”
The MHRA said there had been “a small number” of reports of suspected myocarditis and pericarditis after the administration of either Pfizer-BioNTech or Moderna booster doses.
The agency said this was a “recognised potential risk” with the two mRNA vaccines and it was closely monitoring these events.
“Covid-19 Pfizer/BioNTech Vaccine and Covid-19 Vaccine Moderna are the preferred vaccines in the UK booster programme, and the reporting rates for suspected myocarditis and pericarditis following booster or third doses of these vaccines are lower than those estimated for the first and second doses,” the MHRA said.
“These events are very rare after booster doses. There is no indication that these events are more severe after booster doses compared to first and second doses; most reports describe mild events with a rapid recovery and are similar to those experienced after the first and second doses.”
The MHRA said that reports of anaphylaxis or anaphylactoid reactions remained very rare after booster doses. “Analysis of the data shows that these events are about five times lower after booster doses compared to the first dose,” the agency said.
The agency also said suspected adverse reactions had been reported after the administration of Covid vaccine boosters at the same time as flu vaccines, but no new safety concerns had been identified.
The MHRA said that, up to July 27, it had received Yellow Card reports of 444 cases of major thromboembolic events with concurrent thrombocytopenia in the UK following vaccination with the AstraZeneca Covid-19 vaccine, including 51 that occurred after the second vaccine dose. The patients were aged between 18 and 93 years. Eighty of the patients died, including six who died after the second vaccine dose.
“Of the 444 reports, 220 occurred in females, and 219 occurred in males,” the MHRA said. “The overall case fatality rate was 18%.” In five cases, the sex of the patient was not identified in the report.
Cerebral venous sinus thrombosis was reported in 162 cases (average age 46 years) and 282 patients (average age 54 years) had other major thromboembolic events with concurrent thrombocytopenia.
The overall incidence after first or unknown doses was 15.7 per million doses, the MHRA said.
“Considering the different numbers of patients vaccinated with Covid-19 Vaccine AstraZeneca in different age groups, the data indicates that there is a higher reported incidence rate in the younger adult age groups following the first dose compared to the older groups,” the agency added.
The MHRA puts the incidence rate after the first dose at 21.5 per million doses in people aged 18–49 years as compared to 11.3 per million doses in those aged 50 years and over.
The number of first doses given to people in the 18–49 years age group in the UK is estimated to be 8.5 million while an estimated 16.4 million first doses have been given to patients aged 50 years and above.
“The MHRA advises that this evidence should be taken into account when considering the use of the vaccine,” the agency said. “There is some evidence that the reported incidence rate is higher in females compared to men although this is not seen across all age groups and the difference remains small.”
The overall incidence of thromboembolic events with concurrent low platelets after second doses was 2.1 cases per million doses, the MHRA said.
“Taking into account the different numbers of patients vaccinated with Covid-19 Vaccine AstraZeneca in different age groups, the data indicates that there is a lower reported incidence rate in younger adult age groups following the second dose compared to the older groups (1.0 per million doses in those aged 18–49 years compared to 2.1 per million doses in those aged 50 years and over),” the agency said.
“The number of second doses given to those in the 18–49 years age group is estimated to be 8.1 million while an estimated 16.1 million second doses have been given to patients aged 50+ years.”
The MHRA says the incidence rates reported after the second dose should not be directly compared to those reported after the first dose as the time for follow-up and identification of cases after second doses is more limited and differs across age groups.
The agency said that it had conducted a thorough review of events of cerebral venous sinus thrombosis (CVST) without concurrent low platelet levels following vaccination with the Covid-19 Vaccine AstraZeneca and sought advice from the Commission on Human Medicines’ Vaccine Benefit Risk Expert Working Group.
“The scientific review concluded that there is a possible link between CVST without low platelets and Covid-19 Vaccine AstraZeneca,” the MHRA said.
“The product information for Covid-19 Vaccine AstraZeneca has been updated to include information that CVST events not associated with low levels of blood platelets occurred extremely rarely.”
The MHRA said most of the cases of CVST occurred within the first four weeks after Covid vaccination.
“A potential cause has not been identified,” the agency said. “The MHRA has also confirmed that the evidence to date does not suggest that the Covid-19 Vaccine AstraZeneca increases the risk of venous thromboembolism (i.e. deep vein thrombosis/pulmonary embolism) in the absence of a low platelet count.”
The MHRA said that, after a thorough scientific review, it concluded that there was evidence of a likely link between administration of the AstraZeneca Covid-19 vaccine and blood clotting events, including cerebral venous sinus thrombosis, with concurrent low levels of platelets.
“Anyone who experienced cerebral or other major blood clots occurring with low levels of platelets after their first vaccine dose of Covid-19 Vaccine AstraZeneca should not have further doses,” the MHRA said. “Anyone who did not have these side effects should come forward for their second dose when invited.”
Reports of suspected thromboembolic events with concurrent thrombocytopenia (after vaccination with the AstraZeneca Covid-19 vaccine) in the UK up to and including July 27.
The MHRA also said that, as of July 27, it had received Yellow Card reports of 32 cases of major thromboembolic events (blood clots) with concurrent thrombocytopenia in the UK following administration of the Pfizer-BioNTech vaccine. Thirteen of the patients were female and 18 were male. The patients’ age range was 18 to 91 years and four of them died.
The agency added that, as of July 27, it had received Yellow Card reports of seven cases of major thromboembolic events (blood clots) with concurrent thrombocytopenia in the UK after administration of the Moderna vaccine. Five of the patients were adult males and two were adult females. The patients were aged between 28 and 95 years, the MHRA said.
The MHRA said it had received 4,011 UK reports of suspected adverse reactions to the Pfizer-BioNTech vaccine in which the person affected was reported to be under 18 years old. The person affected was also reported to be aged under 18 years in 264 cases of suspected adverse reactions to the AstraZeneca Covid-19 vaccine, 33 cases following administration of the Moderna vaccine, and 34 cases in which the vaccine brand was unspecified.
The agency said there was a “recognised potential risk” of myocarditis and pericarditis in individuals aged under 18 years after administration of the Pfizer-BioNTech and Moderna vaccines and the agency was closely monitoring these events.
In the case of the Pfizer-BioNTech vaccine, reporting rates for five- to 11-year-olds, 12- to 15-year-olds and 16- to 17-year-olds were all fewer than one per 1,000 doses, the MHRA said.
This was approximately half the reporting rate for the vaccine when administered to those aged 18 years and above, the agency added.
“As Covid-19 Vaccine AstraZeneca and Covid-19 Vaccine Moderna are not the preferred vaccines in under 18s there is insufficient experience in this age group to be able to make similar estimates,” the MHRA said.
The MHRA said that, as of July 26, an estimated 4.1 million first doses, 2.7 million second doses, and 0.2 million additional or booster doses of the Pfizer-BioNTech vaccine had been administered to under-18s in the UK.
About 11,600 first doses and 8,700 second doses of the AstraZeneca Covid-19 vaccine plus 2,100 first doses, 2,000 second doses, and 2,400 additional or booster doses of the Moderna vaccine had been given to under-18s in the UK, the MHRA said.
There had been extremely limited use of the AstraZeneca vaccine as a booster for those aged under 18 years in the UK, the agency added.
MYOCARDITIS AND PERICARDITIS
The MHRA said that, as of July 27, it had received 816 reports of myocarditis and 553 reports of pericarditis after administration of the Pfizer-BioNTech vaccine as well as ten reports of carditis, five reports of viral myocarditis, four reports of viral pericarditis and infective pericarditis, three reports of endocarditis, two reports of mycotic myocarditis, one report of a fatal case of non-infective endocarditis, one report of constrictive pericarditis, one report of streptococcal endocarditis, one report of eosinophilic myocarditis, one report of hypersensitivity myocarditis and one report each of pleuropericarditis, septic myocarditis, post-infection myocarditis, bacterial myocarditis, lupus pericarditis, and infectious myocarditis. In five of the cases of myocarditis and two of the cases of pericarditis the patient died.
As of July 27, there had been 235 reports of myocarditis and 222 reports of pericarditis after administration of the AstraZeneca Covid-19 vaccine, the MHRA added. There were also eight reports of endocarditis, five reports of viral pericarditis, three reports of viral myocarditis and carditis, two reports of bacterial endocarditis, two reports of acute endocarditis, and one report of infectious myocarditis, one report of autoimmune myocarditis, one report of post-infection myocarditis, and one report of autoimmune pericarditis. In six of the cases of myocarditis the patient died.
There were 227 reports of myocarditis, 135 reports of pericarditis, three reports of carditis, one report of hypersensitivity myocarditis, one report of pleuropericarditis, one report of viral myocarditis, and one report of endocarditis after administration of the Moderna vaccine, the MHRA said.
The MHRA said that, in the UK, the overall reporting rate across all age groups for suspected myocarditis (including viral myocarditis), after first, second, and booster or third vaccine doses, was ten reports per million doses of the Pfizer-BioNTech vaccine.
For suspected pericarditis, including viral pericarditis and infective pericarditis, the overall reporting rate was seven reports per million doses of the Pfizer-BioNTech vaccine.
In the case of the Moderna vaccine, the overall reporting rate for suspected myocarditis, including hypersensitivity myocarditis and viral myocarditis, was 18 per million doses and for suspected pericarditis, including pleuropericarditis, it was 11 per million doses.
For the AstraZeneca Covid-19 vaccine, the overall reporting rate for suspected myocarditis, including viral myocarditis and infectious myocarditis, was five reports per million doses and for suspected pericarditis, including viral pericarditis, it was also five reports per million doses, the MHRA said.
“When the reporting rate is calculated by age group, the reporting rate for suspected myocarditis and pericarditis is highest in the 18–29-year age group for the Pfizer/BioNTech and Moderna Covid-19 vaccines,” the MHRA said. “A more even spread in reporting rates across the age groups is seen for the AstraZeneca Covid-19 vaccine. For all vaccines there is a trend for decreased reporting in the older age groups.”
The MHRA said there was no indication in the current data about the Pfizer-BioNTech vaccine that there was an increased reporting rate of suspected myocarditis and pericarditis in the under-18s age group overall compared to young adults.
“Furthermore, the reporting rates for the five- to 11-year, 12- to 15-year, and 16- to 17-year age group are lower than that in the young adult 18–29 age group after the first and second doses,” the MHRA said.
“There have been no reports of suspected myo/pericarditis following booster doses in the under-18-year age group.”
The MHRA said it was important to note that Yellow Card data could not be used to compare the safety profile of Covid-19 vaccines as many factors could influence ADR reporting.
The agency noted that two large European epidemiological studies had estimated the excess risk of myocarditis following vaccination with the Pfizer-BioNTech and Moderna Covid vaccines.
One study showed that in a period of seven days after the second dose of the Pfizer-BioNTech vaccine there were about 27 (95% CI 26–28) extra cases of myocarditis in 12- to 29-year-old males per million compared to unvaccinated individuals, the MHRA said.
In the case of the Moderna vaccine there were about 132 (95% CI 130–133) extra cases of myocarditis in 12- to 29-year-old males per million compared to unvaccinated individuals.
In another study, in a period of 28 days after the second dose of the Pfizer-BioNTech vaccine there were 57 [95% CI 39–75] extra cases of myocarditis in 16- to 24-year-old males per million compared to unvaccinated people.
In the case of the Moderna vaccine there were 188 [95% CI 96–280] extra cases of myocarditis in 16- to 24-year-old males per million compared to unvaccinated people.
“These studies have shown that these events are very rare post-vaccination with the mRNA vaccines, and that these events are more frequent in younger males,” the MHRA said. “The findings of these studies are consistent with the trends seen in the Yellow Card data.”
Myocarditis and pericarditis happened very rarely in the general population, the MHRA said, and it was estimated that, in the UK, there were about 60 new cases of myocarditis diagnosed per million patients per year and about 100 new cases of pericarditis diagnosed per million patients per year.
The agency said that myocarditis is also known to be associated with SARS-CoV-2 infection, with an estimated 1,500 cases of myocarditis per million patients with Covid-19.
The MHRA has made revisions to the product information for the Moderna and Pfizer-BioNTech vaccines and it now includes “Inflammation of the heart (myocarditis or pericarditis)” in the possible side effects of both vaccines.
Information for UK recipients of the Pfizer-BioNTech vaccine:
Included in the patient information leaflet for the Moderna vaccine:
The MHRA said that, up to and including July 27, it had received 505 reports of Guillain-Barré syndrome after administration of the AstraZeneca Covid-19 vaccine, including five cases that were fatal, and 29 reports of a related disease called Miller Fisher syndrome.
As of July 27, the MHRA also received 107 reports of GBS, including two fatal cases, and six reports of Miller Fisher syndrome following administration of the Pfizer-BioNTech vaccine and 24 reports of GBS after administration of the Moderna vaccine.
The MHRA said that, with independent advice from its Vaccine Benefit Risk Working Group, it would continue to review reports of GBS received after the administration of Covid-19 vaccines “to further assess a possible association”.
“Following the most recent review of the available data the evidence of a possible association has strengthened,” the MHRA said.
Following advice from the Commission on Human Medicines and the Covid-19 Vaccines Benefit Risk Expert Working Group, the product information for the AstraZeneca Covid-19 vaccine was further updated to include GBS in the tabulated list of adverse reactions associated with the vaccine “and to encourage healthcare professionals and the public to look out for signs of GBS”, the agency added.
The MHRA also said it had received 17 reports of capillary leak syndrome (a condition in which blood leaks from the small blood vessels into the body) after administration of the AstraZeneca Covid-19 vaccine. In three cases, the patient had a history of capillary leak syndrome, the agency said.
The agency added: “This is an extremely rare relapsing-remitting condition and triggers for relapses are not well understood.
“As a precautionary measure, the MHRA is advising that Covid-19 Vaccine AstraZeneca is not used in people who have previously experienced episodes of capillary leak syndrome. The product information has been updated to reflect this advice.”
On June 11, 2021, the EMA said the PRAC had concluded that people who have previously had capillary leak syndrome must not be vaccinated with the AstraZeneca Covid-19 vaccine .The committee also concluded that capillary leak syndrome should be added to the product information as a new side effect of the vaccine, together with a warning to raise awareness among healthcare professionals and patients about the risk.
The EMA said the PRAC carried out an in-depth review of six cases of capillary leak syndrome in people who had received the AstraZeneca Covid-19 vaccine. Fourteen reports of capillary leak syndrome were reviewed, but only six had sufficient information for further assessment and were considered to be cases of capillary leak syndrome.
Most of the cases occurred in women within four days of vaccination. Three of the patients affected had a history of capillary leak syndrome and one of them died.
On July 9, the EMA said the PRAC had recommended that people who had previously had capillary leak syndrome must not be vaccinated with the Janssen Biotech vaccine and that capillary leak syndrome should be added to the product information as a new side effect of the vaccine together with a warning to raise awareness among healthcare professionals and patients of this risk.
The PRAC reviewed three cases of capillary leak syndrome in people who had received the Janssen Biotech vaccine, which occurred within two days of vaccination. One of those affected had a history of capillary leak syndrome and two of them died.
The EMA also updated healthcare professionals about measures to monitor thrombosis with thrombocytopenia syndrome (TTS) after administration of the Janssen Biotech vaccine.
“Individuals diagnosed with thrombocytopenia within three weeks after vaccination with Covid-19 Vaccine Janssen should be actively investigated for signs of thrombosis,” the EMA said. “Similarly, individuals who present with thrombosis within three weeks of vaccination should be evaluated for thrombocytopenia.”
In its latest summary, the MHRA said it would continue to monitor the incidence of Bell’s palsy (BP) after Covid-19 vaccination.
“Whilst reporting of BP following Covid-19 vaccination is rare, evidence based on the latest available data shows that there may be an increased risk of BP following Covid-19 vaccination,” the MHRA said.
“To raise awareness of this potential adverse event amongst healthcare professionals and patients, facial paralysis has been included in the product information for Covid-19 Vaccine AstraZeneca, Covid-19 Vaccine Pfizer/BioNTech, and Covid-19 Vaccine Moderna.”
The MHRA also said it had also been closely monitoring reports of immune thrombocytopenia (ITP) after Covid vaccination.
“A recent thorough review of all the available evidence confirmed that this type of event is reported extremely rarely for Covid-19 Vaccine AstraZeneca in the UK, at approximately five reports per million doses,” the MHRA said.
“In approximately 10–20% of the reports patients had a history of ITP or an underlying condition known to be associated with ITP.”
The MHRA said that, following the most recent review, the available data suggested a possible link between Covid-19 vaccine AstraZeneca and ITP, and the product information for the vaccine had been updated to include information about the occurrence of ITP.
The MHRA noted that it has been monitoring reports of suspected transverse myelitis following Covid-19 vaccination.
The agency said that, as of July 27, it had received 127 reports of suspected transverse myelitis after the administration of Covid-19 Vaccine AstraZeneca, 40 reports following administration of the Pfizer-BioNTech vaccine and seven reports following administration of the Moderna vaccine.
“Whilst the incidence rate of this adverse event with any of the COVID-19 vaccines used in the UK remains extremely rare (less than 1 report per 100,000 doses of each vaccine), the available evidence reviewed by the MHRA suggests an association between TM and Covid-19 AstraZeneca vaccine is possible,” the MHRA said.
“Due to the serious nature of this adverse event and as a precaution, the product information has been updated to raise healthcare professionals’ and patients’ awareness of the signs and symptoms associated with TM, which may include muscle weakness, localised or radiating back pain, bladder and bowel symptoms and changes in sensation.”
The MHRA said it was recommended that patients who had an episode of transverse myelitis following the first dose of Covid-19 Vaccine AstraZeneca should not receive a second dose of the vaccine.
The MHRA said that, as of July 27, it had received reports of 51,385 menstrual disorders after administration of the three Covid vaccines. These included heavier than usual periods, delayed periods, and unexpected vaginal bleeding.
“These suspected reactions have been reported in 40,042 individual Yellow Card reports (as each report may contain more than one suspected reaction),” the MHRA said.
This was following the administration of about 74.8 million Covid-19 vaccine doses to women up to July 26, the MHRA said.
“The number of reports of menstrual disorders and vaginal bleeding is low in relation to both the number of people who have received Covid-19 vaccines to date and how common menstrual disorders are generally,” the agency added.
“The rigorous evaluation completed to date does not support a link between changes to menstrual periods and related symptoms and Covid-19 vaccines.”
The MHRA said the menstrual changes reported after Covid vaccination were mostly transient in nature and there was no evidence to suggest that Covid-19 vaccines would affect women’s fertility and their ability to have children.
“Whilst uncomfortable or distressing, period problems are extremely common and stressful life events can disrupt menstrual periods,” the agency said.
Changes to the menstrual cycle had also been reported following infection with SARS-CoV-2 and in people affected by long Covid, the MHRA added.
On February 11, 2022, the EMA said the PRAC was assessing reported cases of heavy menstrual bleeding and the absence of menstruation after administration of the Comirnaty and Spikevax vaccines. The committee had previously analysed reports of menstrual disorders in the context of the safety reports for Covid-19 vaccines approved in the EU and concluded at that time that the evidence did not indicate a causal link between the vaccines and menstrual disorders.
“In view of spontaneous reports of menstrual disorders with both vaccines and of findings from the literature, the PRAC decided to further assess occurrences of heavy periods or amenorrhea following vaccination,” the EMA said.
The agency added: “Menstrual disorders are very common and can occur with a wide range of underlying medical conditions as well as from stress and tiredness.” Cases of menstrual disorders had also been reported following SARS-CoV-2 infection, the EMA said.
“After reviewing the available evidence, the PRAC decided to request an in-depth evaluation of all available data, including reports from spontaneous reporting systems, clinical trials and the published literature.
“At this stage, it is not yet clear whether there is a causal link between the Covid-19 vaccines and the reports of heavy periods or amenorrhea. There is also no evidence to suggest that Covid-19 vaccines affect fertility.”
COVID VACCINATION DURING PREGNANCY AND BREASTFEEDING
The MHRA said that the numbers of Yellow Card reports for pregnant women were low in relation to the number of pregnant women who had received Covid-19 vaccines to date.
More than 118,000 women in England and Wales had given birth up to the end of February 2022 after receiving at least one dose of a Covid-19 vaccine during or shortly before pregnancy and more than 40,000 women in Scotland and Wales had received at least one dose whilst pregnant up to the end of March 2022, the agency added.
Pregnant women had reported similar suspected reactions to the vaccines as people who were not pregnant, the agency added.
“Reports of miscarriage and stillbirth are also low in comparison to how commonly these events occurred in the UK outside of the pandemic,” the MHRA said.
“A few reports of commonly occurring congenital anomalies and obstetric events have also been received. There is no pattern from the reports to suggest that any of the Covid-19 vaccines used in the UK, or any reactions to these vaccines, increase the risk of miscarriage, stillbirths, congenital anomalies or birth complications.”
The MHRA said that miscarriage was estimated to occur in about twenty to 25 in 100 pregnancies in the UK and most occurred in the first 12 to 13 weeks of pregnancy.
“Published studies from the USA and Norway have compared miscarriage rates for vaccinated and unvaccinated women who were pregnant over the same time periods,” the agency added.
“Both studies found that the occurrence of miscarriage was equally likely amongst unvaccinated women as amongst women at the same stage of pregnancy who were vaccinated in the previous three to five weeks.”
The MHRA said the studies included data about more than 15,000 women who received either the Pfizer-BioNTech or Moderna vaccine.
“These studies provide strong evidence for no increased risk of miscarriage in association with the mRNA vaccines in current use,” the MHRA said. “Data on the Covid-19 Vaccine AstraZeneca is less extensive but is consistent with these findings.”
The agency said that evidence for pregnancy outcomes other than miscarriage was accumulating as more pregnancies reached full term. “Currently available evidence does not suggest any increased risks of pregnancy complications, stillbirths, preterm births or adverse neonatal outcomes following vaccination in later pregnancy,” the MHRA added.
The MHRA noted that stillbirths were estimated to occur in about one in 200 pregnancies in the UK.
“Information from surveillance by UKHSA (formerly Public Health England) has found similar rates of stillbirth amongst (more than 125,000) women who were vaccinated before or during pregnancy and those who gave birth over the same period and were unvaccinated.” the agency said.
The MHRA added that surveillance by Public Health Scotland and the Covid-19 in Pregnancy in Scotland (COPS) study had found similar rates of perinatal mortality (including stillbirths) amongst more than 15,700 women who were vaccinated during pregnancy and those who gave birth over the same period and were unvaccinated and not infected with SARS-CoV-2.
The agency also cited a study from Israel that looked at live birth outcomes for more than 2,000 women who were vaccinated in their first trimester compared to more than 3,500 unvaccinated women who became pregnant around the same time.
“The study found no differences between vaccinated and unvaccinated women in rates of preterm births, neonatal hospitalisation or mortality, or babies born with birth defects,” the MHRA said.
The MHRA said it had received about 4,000 Yellow Card reports from women breastfeeding at the time of vaccination.
“Most of these women reported only suspected reactions in themselves which were similar to reports for the general population, with no effects reported on their milk supply or in their breastfed children,” the agency said.
“A small number of women have reported decreases in their milk supply, most of which were transient, or possible reactions in their breastfed child,” the MHRA said. “A number of factors can affect milk supply and infant behaviour, including general maternal health, amount of sleep, and anxiety.
“The symptoms reported for the children (high temperature, rash, diarrhoea, vomiting, and general irritability) are common conditions in children of this age, so some of the effects reported may have occurred by coincidence.”
The MHRA said there was no current evidence that Covid vaccination while breastfeeding caused any harm to breastfed children or affected a woman’s ability to breastfeed.
The agency said the product information for the Pfizer-BioNTech and Moderna vaccines had been updated “to reflect that the available data are reassuring on safety and that the vaccines can be used during breastfeeding”.
The MHRA added: “Covid-19 vaccines do not contain live components and there is no known risk associated with being given a non-live vaccine whilst breastfeeding.
“The current advice of the Joint Committee on Vaccination and Immunisation is that breastfeeding parents may be offered any suitable Covid-19 vaccine depending on their age.”
The MHRA also said it had been reviewing reports of skin reactions occurring around the vaccination site that appeared a little while after vaccination. It said most of the reports referred to the Moderna vaccine and the product information for that vaccine had been updated to highlight the possibility of delayed injection site reactions.
“These reactions are suggestive of a delayed hypersensitivity reaction that occurs four–11 days after vaccination,” the MHRA said.
“The reactions are characterised by a rash, swelling and tenderness that can cover the whole upper arm and may be itchy and/or painful and warm to the touch.”
The MHRA said the reactions were usually self-limiting and resolved within a day or two, but, in the case of some patients, the rashes could take slightly longer to disappear.
“Individuals who experience this reaction after their first dose may experience a similar reaction in a shorter time frame following the second dose,” the MHRA said.
“However, none of the reports received have been serious and people should still take their second dose when invited. Those who experience delayed skin reactions after their Covid-19 vaccination which do not resolve within a few days should seek medical advice.”
The MHRA also said there had been rare reports of extensive swelling of the vaccinated limb after administration of the Pfizer-BioNTech vaccine.
“The product information has been updated to include ‘extensive swelling of the vaccinated limb’ as a side effect of the vaccine,” the MHRA said. “This type of swelling is also recognised to occur with other (non-Covid-19) vaccines.”
The MHRA says that, for all Covid-19 vaccines, most reports relate to injection-site reactions and generalised symptoms such as a ‘flu-like’ illness, headache, chills, fatigue, nausea, fever, dizziness, weakness, aching muscles, and a rapid heartbeat.
REPORTS ABOUT THE ASTRAZENECA COVID-19 VACCINE
The reports about the AstraZeneca Covid-19 vaccine include 183,693 nervous system disorders (240 fatal), 14,071 vascular disorders (80 fatal), 7,893 blood disorders (16 fatal), 11,621 cardiac disorders (212 fatal), 15,043 eye disorders, including 331 cases of blindness, and 10,894 ear disorders (one fatal) that include 913 cases of hearing loss, 4,540 cases of tinnitus, and 2,350 cases of vertigo.
There are 1,389 reports of a cerebrovascular accident (55 fatal), 207 reports of cerebral haemorrhage (58 fatal), and 169 reports of an ischaemic stroke (eight fatal). The cardiac disorders include 200 reports of cardiac arrest (43 fatal).
The reports also include 81,246 gastrointestinal disorders (15 fatal), 3,463 immune system disorders (six fatal), 104,997 muscle and tissue disorders (one fatal), 30,069 respiratory disorders (150 fatal), 53,633 skin disorders, 18,595 psychiatric disorders (five fatal), 20,669 cases of infection (118 fatal) that include 1,707 reports of herpes zoster (plus other herpes cases listed separately), and 20,939 reports of reproductive and breast disorders that include 1,342 cases of vaginal haemorrhage and 507 cases of breast pain. There are 239 reports of a miscarriage (spontaneous abortion).
There are 729 reports of an anaphylactic reaction (two fatal) and 644 reports of Bell’s palsy (there are also another 379 cases described as facial paralysis).
There are 895 reports of thrombocytopenia (nine fatal), 226 reports of immune thrombocytopenia (one fatal), 12 cases of thrombotic thrombocytopenic purpura (TTP), and 1,989 reports of non-site specific thrombosis (44 fatal).
There are 16,680 reports listed of adverse reactions related to menstruation and uterine bleeding, including 4,861 reports of heavy menstrual bleeding, 3,352 cases of delayed menstruation, and 2,454 cases of irregular menstruation.
There are also 447 reports of menopausal effects listed, including 312 cases of postmenopausal haemorrhage.
REPORTS ABOUT THE PFIZER-BIONTECH VACCINE
The reports about the Pfizer-BioNTech vaccine include 82,466 nervous system disorders (98 fatal), 7,739 vascular disorders (23 fatal), 17,206 blood disorders (five fatal), 13,658 cardiac disorders (171 fatal), 8,226 eye disorders, including 172 cases of blindness, and 6,801 ear disorders, including 694 cases of hearing loss, 2,579 cases of tinnitus, and 1,690 cases of vertigo.
There are 520 reports of a cerebrovascular accident (22 fatal), 70 reports of cerebral haemorrhage (18 fatal), and 68 reports of an ischaemic stroke (three fatal). The cardiac disorders include 135 reports of cardiac arrest (47 fatal).
The reports also include 43,010 gastrointestinal disorders (18 fatal), 2,563 immune system disorders (two fatal), 56,824 muscle and tissue disorders (one fatal), 22,282 respiratory disorders (67 fatal), 34,866 skin disorders (three fatal), 10,448 psychiatric disorders (three fatal), 12,924 cases of infection (121 fatal) that include 1,671 reports of herpes zoster (plus other herpes cases listed separately), and 31,552 reports of reproductive and breast disorders (one fatal) that include 1,822 cases of vaginal haemorrhage and 880 cases of breast pain. There are 500 reports of a miscarriage, one of which is listed as a fatality.
There are 570 reports of an anaphylactic reaction (two fatal) and 657 cases of Bell’s palsy (there are also another 490 cases categorised as facial paralysis).
There are 244 reports of thrombocytopenia (two fatal), 89 reports of immune thrombocytopenia, nine cases of TTP, and 559 reports of non-site specific thrombosis (12 fatal).
There are 26,578 reports listed of adverse reactions related to menstruation and uterine bleeding, including 6,415 reports of heavy menstrual bleeding, 5,798 cases of delayed menstruation, and 4,136 cases of irregular menstruation.
There are also 195 reports of menopausal effects listed, including 117 cases of postmenopausal haemorrhage.
The MHRA has changed the frequency of publication of its summary of Yellow Card reporting and is now publishing it monthly.
Janssen and AstraZeneca vaccines under scrutiny
On May 5, 2022, the FDA in the US announced that it had limited the authorised use of the Janssen Covid-19 vaccine to people aged 18 years and above for whom other approved Covid-19 vaccines were not accessible or clinically appropriate, and to individuals 18 years and older who elected to receive the Janssen vaccine because they would otherwise not receive a Covid-19 vaccination.
The decision was made because of the risk of thrombosis with thrombocytopenia syndrome.
“After conducting an updated analysis, evaluation and investigation of reported cases, the FDA has determined that the risk of thrombosis with thrombocytopenia syndrome (TTS), a syndrome of rare and potentially life-threatening blood clots in combination with low levels of blood platelets with onset of symptoms approximately one to two weeks following administration of the Janssen Covid-19 vaccine, warrants limiting the authorised use of the vaccine,” the FDA said.
The FDA said that the fact sheet for healthcare providers now included a warning statement that summarised information about the TTS risk. Also, updated information about the risk of blood clots with low levels of blood platelets had been added to the fact sheet for recipients and caregivers, the agency added.
The CDC had said earlier that, as of April 7, 2022, there had been 60 confirmed reports in the US of people developing TTS after receiving the Janssen Biotech vaccine.
A review of reports indicated a causal relationship between the J&J/Janssen Covid-19 Vaccine and TTS, the CDC said.
“CDC has also identified nine deaths that have been caused by or were directly attributed to TTS following J&J/Janssen Covid-19 vaccination,” the CDC added. “Women ages 30–49 years, especially, should be aware of the increased risk of this rare adverse event. There are other Covid-19 vaccine options available for which this risk has not been seen.”
Four confirmed cases of TTS had been reported to VAERS following administration of mRNA vaccines after more than 544 million doses of mRNA Covid vaccines had been administered in the US, the CDC said. Three cases occurred after the administration of the Moderna vaccine and one after administration of the pfizer-BioNTech vaccine.
“Based on available data, there is not an increased risk for TTS after mRNA Covid-19 vaccination,” the CDC said.
The FDA said on May 5 that it has had determined that the reporting rate of TTS was 3.23 per million doses of the Janssen vaccine administered and the reporting rate of TTS deaths was 0.48 per million doses of the vaccine administered.
“In making the determination to limit the authorised use of the Janssen Covid-19 vaccine, the agency considered that reporting rates of TTS and TTS deaths following administration of the the Janssen Covid-19 vaccine are not appreciably lower than previously reported,” the agency added.
“Furthermore, the factors that put an individual at risk for TTS following administration of the Janssen Covid-19 vaccine remain unknown,” the FDA said.
“The FDA also considered that individuals with TTS may rapidly deteriorate, despite prompt diagnosis and treatment, that TTS can lead to long-term and debilitating health consequences and that TTS has a high death rate.”
On December 16, 2021, the CDC had endorsed the ACIP’s recommendation that mRNA Covid vaccines should be used in preference to the Janssen vaccine.
“ACIP’s unanimous recommendation followed a robust discussion of the latest evidence on vaccine effectiveness, vaccine safety and rare adverse events, and consideration of the US vaccine supply,” the CDC said.
The CDC said there was an abundant supply of mRNA vaccines in the US, with nearly 100 million doses available for immediate use.
“Given the current state of the pandemic both here and around the world, the ACIP reaffirmed that receiving any vaccine is better than being unvaccinated,” the CDC said.
“Individuals who are unable or unwilling to receive an mRNA vaccine will continue to have access to Johnson & Johnson’s Covid-19 vaccine.”
On November 14, 2021, the CDC released a review of reported US cases of TTS after Covid vaccination up to August 2021. Continued monitoring had identified nine deaths causally associated with administration of the Janssen Biotech vaccine.
Johnson & Johnson said it remained confident in the overall positive benefit-risk profile of its Covid-19 vaccine.
“Studies have shown that the Johnson & Johnson Covid-19 vaccine generates strong antibody and cellular immune responses and long-lasting immune memory and breadth of protection across variants,” the company said.
The global head of Janssen research and development, Mathai Mammen, said: “The safety and wellbeing of those who use the Johnson & Johnson vaccine continues to be our number one priority.
“We appreciate today’s discussion and look forward to working with the CDC on next steps. In addition, we strongly support education and generating awareness of rare events, such as thrombosis with thrombocytopenia syndrome TTS and how to effectively manage it.”
The PRAC in the UK said it had concluded that there was a possible link between the Janssen vaccine and rare cases of venous thromboembolism (VTE).
The committee also recommended updating the product information of the Janssen and AstraZeneca-Oxford vaccines to include ITP as “an adverse reaction with an unknown frequency”.
Also, a warning statement has been issued stating that cases of very low levels of blood platelets have been reported “very rarely, usually within the first four weeks following vaccination with Covid-19 Vaccine Janssen or Vaxzevria”.
The developments were announced on October 1 by the EMA in its report about the PRAC meeting that was held from September 27 to 30.
VTE is a condition in which a blood clot forms in a deep vein, usually in a leg, arm, or groin, and may travel to the lungs causing a blockage of the blood supply, with possible life-threatening consequences.
“This safety issue is distinct from the very rare side effect of thrombosis with thrombocytopenia syndrome,” the EMA said.
“VTE was included in the risk management plan for Covid-19 Vaccine Janssen as a safety concern to be investigated, based on a higher proportion of cases of VTE observed within the vaccinated group versus the placebo group in the large clinical study which was used to authorise this vaccine. The issue has been kept under close monitoring.”
The PRAC reviewed evidence from two large studies. In the second study, there was no increase in venous thromboembolic events among individuals who received the Janssen vaccine, the EMA reported.
“The PRAC also reviewed evidence from the post marketing setting,” the EMA said. “When taking all evidence into account, the committee concluded that there is a reasonable possibility that rare cases of VTE are linked to vaccination with COVID-19 Vaccine Janssen.
“The committee is therefore recommending listing VTE as a rare side effect of COVID-19 Vaccine Janssen in the product information, together with a warning to raise awareness among healthcare professionals and people taking the vaccine, especially those who may have an increased risk of VTE.”
The PRAC said it recommended that, if an individual had a history of ITP, “the risk of developing low platelet levels should be considered before vaccination”, and there should be platelet monitoring after administration of either the Janssen or AstraZeneca vaccine.
The PRAC agreed on direct healthcare professional communications (DHPCs) containing safety information for the Janssen and AstraZeneca-Oxford vaccines.
“For ITP, the DHPC highlights that cases of ITP have been reported within the first four weeks after receiving Covid-19 Vaccine Janssen, and that it included serious cases with very low platelet counts,” the EMA reported.
“For VTE, it is described that VTE has been observed rarely following vaccination with Covid-19 Vaccine Janssen and that the risk of VTE should be considered for individuals with increased risk factors for thromboembolism (blood clots).”
The PRAC said that people diagnosed with thrombocytopenia within three weeks of administration of the Janssen vaccine should be actively investigated for signs of thrombosis.
“Similarly, individuals who present with thrombosis within three weeks of vaccination should be evaluated for thrombocytopenia,” the EMA said. “This is important, to assess a potential diagnosis of thrombosis with thrombocytopenia syndrome (TTS), which requires specialised clinical management.”
The PRAC has also warned healthcare professionals about cases of thrombocytopenia, including ITP, that have been reported after administration of the AstraZeneca vaccine, “typically within the first four weeks after vaccination”.
The EMA stated: “If an individual has a history of a thrombocytopenic disorder, healthcare professionals are advised to consider the risk of developing low platelet levels such as ITP, before administering the vaccine. Additionally, platelet monitoring is recommended after vaccination in an individual who has a history of ITP.”
A total 17 countries halted use of the AstraZeneca-Oxford vaccine because of reports of people suffering severe blood clots after vaccination.
The countries are Germany, France, Spain, Norway, Denmark, Iceland, Austria, Ireland, Estonia, Lithuania, Luxembourg, Latvia, the Netherlands, Italy, Bulgaria, Sweden, and Portugal.
Also, AstraZeneca halted the trial in Britain in which its vaccine was being tested on children.
On April 14, Denmark stopped using the AstraZeneca-Oxford vaccine and, on May 3, the Danish Health Authority said it was also excluding the Janssen Biotech vaccine from its vaccination programme.
The authority said it had concluded that the benefits of using the Janssen Biotech vaccine did not outweigh the risk of causing the possible adverse effect (thrombosis with low platelets), in those who received it.
The health authority said it had reviewed the use of the Janssen Biotech vaccine in the country’s Covid-19 vaccination programme based on international data and statements released in the previous month and a team of Danish experts had contributed to the evaluation of the vaccine.
The authority’s deputy director-general, Helene Probst, said: “In the midst of an epidemic, this has been a difficult decision to make, especially since we have also had to discontinue using the Covid-19 vaccine from AstraZeneca.
“However, taking the present situation in Denmark into account, what we are currently losing in our effort to prevent severe illness from Covid-19 cannot outweigh the risk of causing possible side effects in the form of severe blood clots in those we vaccinate. One should also bear in mind that, going forward, we will first and foremost be vaccinating younger and healthy people.”
The decision to exclude the Janssen Biotech vaccine from Denmark’s vaccination programme did not rule out its possible future use, Probst said.
“New knowledge may emerge, or the situation in Denmark may change, for example, in terms of infection pressure, disease burden, epidemic control, or other vaccines’ availability,” she said.
If strict requirements were met, the authority might use the vaccine in clinical trials, she added.
Reuters reported that, at a meeting on May 3, lawmakers agreed to allow voluntary use of the Janssen Biotech and AstraZeneca-Oxford vaccines.
On June 25, Denmark’s National Board of Health issued the following statement: “On 14 April 2021 and 3 May 2021, the Danish Health and Medicines Authority decided to continue the general vaccination programme against Covid-19 without Covid-19 Vaccine Janssen and Vaxzevria … After a thorough update of the data base and the professional assessments, the National Board of Health maintains that assessment.”
The board said that, based on updated data from the US and the EU as well as assessments from the EMA and the US health and drug authorities, it could be established with certainty that both the Janssen Biotech and AstraZeneca-Oxford vaccines cause the vaccine-induced immune thrombotic thrombocytopenia (VITT) syndrome.
“Based on available data, there is no evidence that there is a gender difference in relation to the risk of VITT, but it must generally be assumed that the risk is greater in younger people than in older people,” the health board said.
“Based on the current data base, it can also not be concluded with certainty whether the risk of VITT after vaccination with Covid-19 Vaccine Janssen is lower, comparable, or higher than the risk of vaccination with Vaxzevria, but, in the updated analyses, the National Board of Health has assumed that the risk of Covid-19 Vaccine Janssen can be approximately half the risk of Vaxzevria.”
In Belgium, the Superior Health Council had recommended that the AstraZeneca-Oxford vaccine should only be given to people younger than 55, but later made an about-turn and said it would be administered to older people.
Belgian health ministers said on May 27, however, that the Janssen Biotech Covid vaccine would only be administered to people aged 41 years and above.
Belgium’s health ministers said the country’s inter-ministerial conference had decided to temporarily administer the Janssen Biotech vaccine to people aged 41 years and above pending a more detailed benefit-risk analysis by the EMA.
The decision followed the death in Belgium of a 37-year-old woman who suffered from blood clotting with low platelets after administration of the Janssen Biotech vaccine. She was the wife of a Slovenian diplomat in Brussels.
The EMA said: “The EMA and the Belgian and Slovenian medicines agencies are currently reviewing this first fatal case reported within the EU together with other case reports of blood clots, as part of regular intensified monitoring activities.”
Indonesia delayed the rollout of the AstraZeneca-Oxford vaccine and Venezuela announced that it would not authorise its use.
On May 16, Indonesia announced that it had temporarily halted distribution and use of one batch of the AstraZeneca-Oxford vaccine (batch CTMAV547) to run tests for toxicity following reports of adverse effects after vaccination.
The country’s health ministry said the batch consisted of 448,480 vaccine doses that arrived in Indonesia on April 26 as part of a delivery of more than 3.85 million doses, made via the COVAX Facility.
In May 2021, the product information for the AstraZeneca-Oxford vaccine was updated “with regard to the very rare risk of TTS”, the EMA said.
In September, the PRAC said the product information should be further updated and the statement that reported TSS cases occurred mostly in women under 60 years of age should be removed “since the age and sex imbalance seemed smaller than previously observed”.
The EMA said this conclusion was based on the latest analyses of spontaneously reported TTS cases, which included 43% of the cases occurring in males and 37% in vaccinated persons older than 60 years, “and on data analyses in the scientific literature which did not identify a large difference of TTS cases by sex”.
Research in Germany and Austria
On April 9, 201, two teams of researchers who studied 11 patients in Germany and Austria and five in Norway who had all received the AstraZeneca-Oxford vaccine published papers in The New England Journal of Medicine.
Both teams of scientists found that the patients had unusual antibodies that trigger clotting reactions.
Of the 11 patients in Germany and Austria, nine were women, with a median age of 36 years.
Between five and 16 days after vaccination, ten of the patients presented with one or more thrombotic events. One patient had a fatal intracranial haemorrhage. All the patients had concomitant thrombocytopenia. None of the patients had received heparin before symptom onset.
Of the patients with one or more thrombotic events, nine had cerebral venous thrombosis, three had splanchnic vein thrombosis, three had pulmonary embolism, and four had other thromboses. Six of the patients died. Five patients had disseminated intravascular coagulation.
The researchers who studied the German and Austrian patients were led by Andreas Greinacher, who heads the Institute of Immunology and Transfusion Medicine at the Greifswald University Hospital in Germany.
Greinacher et al. suggested that some of the virus particles in the vaccine dose might break apart and release their DNA, triggering the production of antibodies.
They wrote that interactions between the vaccine and platelets or between the vaccine and platelet factor 4 (PF4) could play a role. The vaccine recipients who had clotting reactions had antibodies to PF4, the researchers found.
“One possible trigger of these PF4-reactive antibodies could be free DNA in the vaccine,” Greinacher et al. wrote.
As Chongxu Shi et al. point out in an article published in Frontiers in Immunology on October 7, 2020, extracellular DNA has been shown to contribute to the process of immunothrombosis.
Alternatively, Greinacher et al. said, antibodies might already be present in the patients and the vaccine may boost them.
“Whether these antibodies are autoantibodies against PF4 induced by the strong inflammatory stimulus of vaccination or antibodies induced by the vaccine that cross-react with PF4 and platelets requires further study,” Greinacher et al. wrote.
The researchers suggested naming “this novel entity” VITT to avoid confusion with heparin-induced thrombocytopenia.
Nina H. Schultz et al. in Norway studied five patients who presented with venous thrombosis and thrombocytopenia seven to ten days after receiving a first dose of the AstraZeneca-Oxford vaccine.
The patients were health care workers aged 32 to 54 years. All of them had high levels of antibodies to platelet factor 4-polyanion complexes, Schultz et al. said. Four of the patients had severe cerebral venous thrombosis with intracranial haemorrhage and three of them died. None of the patients had previous exposure to heparin.
One of the patients – a 32-year-old man – had severe thrombocytopenia and thrombosis of several branches of the portal vein and in the splenic vein, the azygos vein, and the hemiazygos vein. After treatment, his platelet count returned to normal and an abdominal CT scan indicated partial resolution of the thrombosis. He was discharged from hospital on day 12.
Greinacher and 23 other scientists from Germany published a preprint on Research Square on April 20 in which they state clearly that, rarely, the AstraZeneca-Oxford vaccine causes VITT that – like autoimmune heparin-induced thrombocytopenia – “is mediated by platelet-activating anti-platelet factor 4 (PF4) antibodies”.
They say their research has shown that AstraZeneca-Oxford vaccine constituents form antigenic complexes with PF4, that the constituent ethylenediaminetetraacetic acid EDTA, which is acalcium-binding agent and stabiliser, increases microvascular permeability, and that components of the vaccine cause acute inflammatory reactions.
“Antigen formation in a proinflammatory milieu offers an explanation for anti-PF4 antibody production,” Greinacher et al. wrote. “High-titre anti-PF4 antibodies activate platelets and induce neutrophil activation and NETs [Neutrophil extracellular traps] formation, fuelling the VITT prothrombotic response.”
NETs are networks of extracellular fibres, primarily composed of DNA from neutrophils, which bind pathogens.
“We have provided evidence that VITT is not a consequence of antibodies directed against the SARS-CoV-2 spike protein (produced by all vaccines) cross-reacting with PF4,” Greinacher et al. wrote.
The scientists say their findings indicate that it is the adenovirus vector-based vaccines that are at risk of inducing VITT through adenovirus and/or other PF4-DNA interactions.
“The degree of acute inflammatory response induced by the vaccine components appears as an important – potentially remediable – co-factor that could be diminished by reducing impurities and omitting EDTA,” they wrote.
Greinacher et al. say their biophysical analyses showed “formation of complexes between PF4 and vaccine constituents, including virus proteins that were recognised by VITT antibodies”.
They say their research showed that EDTA increased microvascular leakage in mice allowing for the circulation of virus and virus-producing cell culture-derived proteins.
“Antibodies in normal sera cross-reacted with human proteins in the vaccine and likely contribute to commonly observed acute ChAdOx1 nCov-19 post-vaccination inflammatory reactions,” the scientists wrote.
“In the presence of platelets, PF4 enhanced VITT antibody-driven procoagulant NETs formation, while DNase activity was reduced in VITT sera, with granulocyte-rich cerebral vein thrombosis observed in a VITT patient.”
The scientists laid out the sequence of events that their data suggests is mediating VITT. They say that, in step one, a neo-antigen is generated.
“Following intramuscular injection, vaccine components and platelets come into contact, resulting in platelet activation,” they wrote.
“ChAdOx1 nCov-19 vaccine activates platelet by multiple mechanisms including platelet interaction with adenovirus, cell-culture derived proteins (currently, it is unknown which of the > 1,000 proteins identified in the vaccine are involved in platelet activation), and EDTA.”
Activated platelets then release PF4, the scientists say.
In step 2, they say, an inflammatory co-signal is generated that further stimulates the immune response.
“EDTA in the vaccine increases capillary leakage at the inoculation site, likely by endothelial (VE)-cadherin disassembly.”
Greinacher explained further to Changing Times: “The first signal is the inflammatory signal. The vaccine constituents form antigenic complexes with PF4. This is facilitated by the open junctions and endothelial cells. This allows the immune cells to see the PF4.
“This all happens on day one or two after vaccination. The B cells then start to produce antibodies against PF4, which reach high titre in the blood circulation in the second week after vaccination.
“At that time, the vaccine is gone and the platelets are no longer activated by the vaccine. The primary inflammatory response is also gone.
“However, the resulting anti-PF4 antibodies become auto-antibodies that bind to PF4 on the platelets and activate them.”
The body erroneously thinks it is reacting to massive amounts of pathogens in the body, so the immune system overshoots, Greinacher explains.
The scientists say that proteins found in the vaccine include virus proteins, but also proteins originating from the human kidney-derived production cell line T-REx HEK-293.
“Increased vascular permeability facilitates dissemination of these proteins into the blood,” they wrote
Blood dissemination of vaccine components is not unique to the AstraZeneca-Oxford vaccine, they say.
“A ChAdOx1 vector variant (with a hepatitis B vector insert) was detectable by PCR in multiple organs, including liver, heart, and lymph nodes at days two and 29 after intramuscular injection in mice in preclinical studies reported by others,” they wrote.
The scientists say that, in step three, extracellular DNA in NETs binds PF4 “and resulting DNA/PF4 complexes further recruit anti-PF4 antibodies with lower avidity”.
The scientists say their study does have limitations. “The detailed specifications of the ChAdOx1 nCov-19 vaccine are not publicly available and potential impact of about 20 µg human cell culture proteins per vaccination dose remain to be assessed by the responsible regulatory agencies,” they state.
“Furthermore, we did not analyse the constituents of other adenovirus-based Covid-19 vaccines such as the Covid-19 Vaccine Janssen and the Sputnik V vaccine (these were not available to us). More importantly, quality control of vaccines requires the comprehensive methodological expertise of regulatory agencies.”
In another paper published on Research Square on April 9, Greinacher and a separate group of scientists concluded: “The antibody responses to PF4 in SARS-CoV-2 infection and after vaccination with Covid-19 Vaccine AstraZeneca differ.
“Antibodies against SARS-CoV-2 spike protein do not cross-react with PF4 or PF4/heparin complexes through molecular mimicry. These findings make it very unlikely that the intended vaccine-induced immune response against SARS-CoV-2 spike protein would itself induce VITT.”
Molecular geneticist Roland Baker says many scientists have suspected that the SARS-CoV-2 spike protein was involved in production of antibodies that cross-reacted with PF4.
“At this point we have to look at all the possible suspects and dismiss them as the cause one at a time by a process of elimination. The spike was an important contender.
“The finding by Andreas Greinacher et. al. puts to rest concerns that other vaccines producing a spike would have a similar risk. They clearly do not.
“Another factor was tPA [tissue plasminogen activator], but assuming the mechanism of VITT is identical for the Janssen Biotech and AstraZeneca-Oxford vaccines, then we can rule out tPA because it is used in the AstraZeneca-Oxford vaccines, but not in the Janssen Biotech one. So that leaves the adenovirus vector or the DNA as the likely suspects.”
Baker points out in a tweet, however, that the AstraZeneca-Oxford (ChAdOx1) and Janssen Biotech (Ad26.COV2.S) vaccines use substantially different vectors and spikes.
“Ad26.COV2.S features a human Ad26 vector of species D engaging CD46 as its cellular receptor with coding for a membrane-bound SARS-CoV-2 S protein in the prefusion conformation stabilised by two proline substitutions that does not shed S1 due to a KO furin cleavage site,” Baker tweeted.
“ChAdOx1 features a chimpanzee adenovirus vector of species E engaging Coxsackie and adenovirus receptor (CAR) as its cellular receptor and possibly others with coding for a membrane-bound wild-type S protein in the prefusion conformation which may may shed the S1 subunit.
“Shedding of the S1 subunit occurs during native infection and AstraZeneca may shed the S1 subunit as well.”
Postmortems in Italy
Italian researchers have reported on the findings of postmortems into the deaths from VITT of a 50-year-old man and a 37-year old woman in Sicily who both received the AstraZeneca-Oxford vaccine.
In their report, published in the journal Haematologica, Cristoforo Pomara et al. say the main macroscopic finding in both cases was that “venous thrombosis was much more widespread and catastrophic than diagnosed by imaging during life”.
The researchers wrote: “Microscopic findings showed vascular thrombotic occlusions occurring in the microcirculation of multiple organs and increased inflammatory infiltrates.”
They said their findings indicated that the activation of the innate immune system and complement pathway “promote the inflammatory process leading to the microvascular damage of multiple organs”.
Pomara et al. said. that, in both cases the patients had a very low platelet count, very high D-dimer, and low fibrinogen with signs of consumption coagulopathy, better known as disseminated intravascular coagulation (DIC). Both patients also had detectable anti-PF4/polyanion antibodies unrelated to the use of heparin.
The male patient suffered a massive intracerebral haemorrhage, the researchers reported. “Treated with multiple transfusions of platelet concentrates that failed to control bleeding the patient died four days after the onset of symptoms and 16 days after vaccination,” they said.
The previously healthy female patient, who had no history of significant disease or drug intake, developed low back pain and a strong headache ten days after vaccination.
“She became progressively drowsy and ultimately unconscious, and was, therefore, admitted to the emergency room of her local hospital,” Pomara et al. reported.
“A CT scan showed an occlusive thrombus in the superior sagittal venous sinus and a very large haemorrhage in the frontal cerebral lobe. Transported comatose by helicopter to a larger hub hospital she underwent craniotomy in order to control intracranial hypertension and remove the frontal lobe haemorrhage.
“She survived the operation but remained comatose and died 10 days after the first hospital admission and 23 days after vaccination.”
The two patients tested negative for SARS-Cov-2 molecular assays and antibodies to the nucleocapsid and spike proteins, thus ruling out recent exposure to SARS-CoV-2, the researchers added.
“There was neither clinical and laboratory evidence of inherited or acquired thrombophilia nor of intake of prothrombotic medicines,” they said.
“Venous thrombosis was accompanied by severe intracranial bleeding, which was the final cause of death in both and developed after the administration of therapeutic doses of heparin in patient 1 but concomitantly with cerebral vein thrombosis and no anticoagulant in patient 2,” Pomara et al. added.
Deaths after Covid vaccination
The doctor and researcher who uses the Twitter handle @AMcA32449832 tweeted that she was alarmed when she reviewed the first one hundred deaths reported in VAERS after Covid vaccine administration.
— AMM, MD (@AMcA32449832) February 4, 2021
The results of a study of 100 deaths after Covid vaccination in nursing homes in Norway were published on July 7.
Between December 27, 2020, and February 15, 2021, about 29,400 of approximately 35,000 patients in nursing homes in Norway were vaccinated with the Pfizer-BioNTech vaccine.
During the same period, the Norwegian Medicines Agency received 100 reports of suspected fatal adverse reactions to the vaccine. (As of 12 May 12, 2021, the number of such reports had risen to 142.)
An expert group examined the 100 reports. The mean age of the patients was 87.7 years (range 61–103 years).
Reporting on their findings, Torgeir Bruun Wyller et al. said they concluded that a causal link to the vaccine was probable in ten of the cases, possible in 26, and unlikely in 59. They considered five of the cases as unclassifiable.
“Most nursing home patients have a short remaining life expectancy, but vaccination may, in a few cases, have accelerated a process of dying that had already begun,” Wyller et al. said.
“Nursing home patients should still be given priority for vaccination, but the benefits versus risk must be carefully weighed up for the frailest patients.”
The researchers said it must be emphasised that their estimates were very uncertain.
They said the categories ‘probable’ and ‘unlikely’ were used in cases where the expert group considered there to be a clear likelihood one way or the other, and the category ‘possible’ was used where a causal link between vaccination and death was just as likely as unlikely.
“Many of the cases classified as ‘possible’ are therefore very uncertain, and some of them could perhaps also have been categorised as unclassifiable,” Wyller et al. said.
“The group considered far more cases to be either probable or unlikely than the Norwegian Institute of Public Health in its initial assessment. This is probably due to access to more information as well as knowledge of typical clinical courses in frail elderly people.”
Wyller et al. wrote: “The extremely high mortality rate in nursing homes means that random factors will lead to a certain number of deaths shortly after vaccination anyway. It cannot be ruled out that some of the deaths that were classified as probable are in fact due to such random factors.
“Nevertheless, we find it reasonable to assume that adverse effects from the vaccine in very frail patients can trigger a cascade of new complications which, in the worst case, end up expediting death.”
They added: “The adverse reaction reports were submitted within a period of approximately 50 days, during which it can be assumed that 2,000–2,500 nursing home patients died in Norway.
“Whether ten or 36 of these deaths were accelerated by the vaccine, the proportion is still low. In the same period, almost 30,000 nursing home patients were vaccinated, which means that there will most likely have been far more than 100 deaths in nursing homes in a close temporal relationship to vaccination in the relevant time period. Our findings cannot therefore be used to estimate the incidence of vaccine-related deaths.”
One death that made international headlines is that of the British model Stephanie Dubois who died in Cyprus after receiving an AstraZeneca-Oxford vaccination.
Dubois, aged 39, posted on Facebook after she received her first vaccine dose on May 6 that she felt horrendous and on May 14 she was taken to hospital with breathing problems.
Dubois wrote on her Facebook page on May 14 that her white blood cell count was high and doctors didn’t know what was causing it.
“Maybe I’m having a prolonged reaction to my Covid jab last week, or maybe those side effects affected my immune system and I’ve caught something else in the process,” Dubois wrote.
“I am completely drained, no energy and my whole body hurts with sore and weak joints … but it is better than it was this morning. This morning really scared me to be honest.”
Earlier in the day she had written: “Woke up feeling fine and then within an hour I had fully (sic) body shakes, all my joints seized and I was struggling to breathe and was cold to the bone with a persistent headache and dizziness. I was convinced I’d come down with Covid!
“Mum and dad came to look after me and took me for a covid test, which thankfully was negative … but it still doesn’t explain what the problem is.”
According to media reports, by May 19 Dubois had gone into a coma. Local media reported that she had suffered a brain haemorrhage and died on May 22.
A Cypriot health service spokesman has been quoted as saying said that Dubois’ death would be investigated by the EMA.
Another death that made headlines is that on May 21 of a BBC presenter, Lisa Shaw, who died, aged 44, after receiving the AstraZeneca-Oxford vaccine. A coroner concluded that her death was due to complications of the vaccination.
The coroner said that Shaw was previously fit and well. He said it was clearly established that her death was due to a very rare vaccine-induced thrombotic thrombocytopenia.
Shaw, who was a presenter at BBC Radio Newcastle, received her first dose of the vaccine on April 29 and, on May 13, was taken to hospital after suffering headaches for several days.
Her family said: “She was treated by the RVI’s [Royal Victoria Infirmary] intensive care team for blood clots and bleeding in her head.
“Tragically she passed away, surrounded by her family … We are devastated and there is a Lisa-shaped hole in our lives that can never be filled. We will love and miss her always.
A 64-year-old surgeon who was working at the Pieve di Coriano hospital in Mantua, Italy, died a few days after receiving the Pfizer-BioNTech Covid vaccination. A postmortem has been carried out.
According to local media reports, the doctor, Enrico Patuzo, suffered from several chronic conditions, including cardiac problems.
In Genoa, Italy, an 89-year-old woman died after suffering a cerebral haemorrhage. She had received a Covid vaccination. Investigators said they had found no direct causal link between the haemorrhage and the vaccination.
Obstetrician Gregory Michael, aged 56, from Miami in the US died on the night of January 3/4, just over two weeks after receiving a dose of the Pfizer-BioNTech vaccine. Health officials from Florida and the CDC are conducting an investigation.
According to a Facebook post written by his wife, Heidi Neckelmann, Michael died from the complications of idiopathic thrombocytopenic purpura (immune thrombocytopenia).
“He was vaccinated with the Pfizer vaccine … on December 18, three days later he saw a strong set of petechiae on his feet and hands which made him seek attention at the emergency room at MSMC [the Mount Sinai Medical Centre],” Neckelmann wrote.
“The CBC [complete blood count] that was done at his arrival showed his platelet count to be 0 (a normal platelet count ranges from 150,000 to 450,000 platelets per microliter of blood.) He was admitted in the ICU with a diagnosis of acute ITP … .
“A team of expert doctors tried for two weeks to raise his platelet count to no avail. Experts from all over the country were involved in his care. No matter what they did, the platelets count refused to go up. He was conscious and energetic through the whole process but two days before a last resort surgery, he got a haemorrhagic stroke caused by the lack of platelets that took his life in a matter of minutes.”
Neckelmann points out that Michael was a pro vaccine advocate. “That is why he got it himself,” she said. She is convinced that the vaccine caused her husband’s death.
She described Michael as “a very healthy 56 year old, loved by everyone in the community”.He delivered hundreds of healthy babies and worked tireless through the pandemic, she wrote.
“I believe that people should be aware that side effects can happen, that it is not good for everyone and, in this case, destroyed a beautiful life, a perfect family, and has affected so many people in the community.”
In a statement to the South Florida Sun Sentinel, a spokesman for Pfizer said the company was aware of Michael’s death and said it was a “highly unusual clinical case”.
A spokesperson for Pfizer told CBS12 News: “We are actively investigating this case, but we don’t believe at this time that there is any direct connection to the vaccine. There have been no related safety signals identified in our clinical trials, the post-marketing experience thus far or with the mRNA vaccine platform.”
A Johns Hopkins scientist told the New York Times it was a “medical certainty” that Pfizer’s vaccine caused Michael’s death.
However, investigators said they could not determine with certainty what role, if any, the Covid vaccine played in Michael’s death.
“There isn’t enough evidence to rule out or confirm that the vaccine was a contributing factor, a medical examiner’s report said,” the Sun Sentinel reported. “The Medical Examiner Department recently classified the doctor’s as a ‘natural’ death.”
In an article for Case Reports in Hematology published in 2016, Joji Nagasaki et al. report on cases of ITP in three elderly patients that they say was caused by influenza vaccination.
“Influenza vaccination is an underlying etiology of ITP in elderly patients,” the researchers said. “Clinicians should be aware of the association between ITP and influenza vaccinations.”
Post-influenza vaccination ITP in elderly patients may occur within several days or two to three weeks after vaccination, Nagasaki et al. wrote.
ITP is associated with several types of vaccinations, Nagasaki et al. say.
“In previous studies, the risk of developing ITP increased after administration of measles-mumps-rubella (MMR) … hepatitis A, varicella, and diphtheria-tetanus-pertussis vaccines in children and adolescents,” they wrote.
Vaccine adjuvants have been implicated in autoimmune/inflammatory syndrome induced by adjuvants (ASIA), the researchers add.
“The Berlin Case-Control Surveillance Study of drug-associated ITP concluded that influenza vaccinations increase the risk of ITP. Twelve cases of post-influenza vaccination ITP, including our three, have been reported. Features common to most reported cases include PAIgG elevation, time from vaccination to development of ITP, and treatment response.”
Case of ITP have also been linked with HPV vaccination. The manufacturer of Gardasil, Merck, has admitted that it seems “biologically plausible” that non-specific immune stimuli, including vaccinations, could precede cases of ITP in susceptible individuals, but insists that there is insufficient evidence to infer that HPV vaccination can cause the condition.
A large section of Merck’s June–to–December 2018 Periodic Safety Update Report (PSUR) is devoted to reports about people who, after HPV vaccination, developed ITP. There were 94 reports (76 for quadrivalent Gardasil and 18 for Gardasil 9).
Officials in Orange County, California, are meanwhile investigating the death of a 60-year-old healthcare worker who died four days after receiving his second injection of the Pfizer-BioNTech vaccine.
X-ray technologist Tim Zook was hospitalised on January 5 just hours after being vaccinated.
Zook’s wife Rochelle told the Orange County Register that her husband’s health rapidly deteriorated over the next few days. He died on January 9.
The Register reported that, a couple of hours after vaccination, Zook had an upset stomach and trouble breathing. He was taken to hospital and was put on oxygen, then, four hours later, a BiPAP machine was used to help push air into his lungs. Multiple tests came back negative for SARS-CoV-2.
Zook had to be put into in a medically induced coma and was placed on a ventilator, but his blood pressure dropped. His kidneys then started to fail and his condition became critical.
Rochelle Zook told the Register that her husband believed in vaccines, and that she didn’t blame “any pharmaceutical company” for his death, but she added: “When someone gets symptoms two and a half hours after a vaccine, that’s a reaction.”
She said Zook was “quite healthy”, but was slightly overweight and took medication for high blood pressure.
In an email to the Orange County Register, Pfizer said it was aware of Zook’s death and added: “We closely monitor all such events and collect relevant information to share with global regulatory authorities.
The company said that, based on ongoing safety reviews performed by Pfizer, BioNTech and health authorities, the vaccine retained a positive benefit-risk profile for the prevention of Covid-19 infections.
“Serious adverse events, including deaths that are unrelated to the vaccine, are unfortunately likely to occur at a similar rate as they would in the general population,” the company added.
Media in the US reported on February 8, 2021, that health officials in New York had confirmed that a man died shortly after getting the Covid-19 vaccine on February 7.
The man was reported to have collapsed as he was leaving the Hudson Yards vaccination site and died at in hospital a short time later.
New York State health commissioner Howard Zucker was quoted as saying: “Initial indications are that the man did not have any allergic reaction to the vaccine.”
The Los Angeles Times reported on January 26, 2021, that multiple agencies were investigating the death of a person on January 21 in Placer County.
Officials from the Placer County public health department and the Placer County Sheriff’s Office said that the deceased had tested positive for SARS-CoV-2 in late December and had been given a Covid vaccination several hours before he died.
A nurse, Sonia Azevedo, died in Portugal on January 1, 2021, after receiving the Pfizer-BioNTech vaccine on December 30. On January 5, the Portuguese Ministry of justice said that preliminary autopsy results did not establish a direct correlation between the administration of the vaccine and Azevedo’s death.
A 58-year-old doctor died at a private hospital in Karnataka, India, on January 20, 2021, just two days after he received a Covishield vaccination.
The Union Health Ministry said the death of T. A. Jayaprakash was due to cardiac arrest and was unrelated to the vaccination.
There have been numerous media reports about the number of deaths that occurred in Gibraltar in the ten days after vaccination with the Pfizer-BioNTech vaccine began.
It is reported that up until January 9, 2021, when the vaccination drive started, only 12 people had died from Covid-19 in Gibraltar since the beginning of the pandemic. However, from January 10 to 19, 53 deaths were attributed to the disease.
According to local media, there were 27 deaths attributed to Covid-19 in the first week after the vaccine rollout. Within a day of the vaccination drive starting, there were four deaths, all of elderly people.
The government of Gibraltar said on January 10: “It is with deep regret that the government confirms the deaths of four residents of Gibraltar from Covid-19. This brings the total number of deaths related to Covid-19 in Gibraltar to 16.
“The first was a male resident of Elderly Residential Services, aged 90–95 years old, who died last night of Covid-19 pneumonia with septicemia.
“The second was a man, aged 70–75 years old, who was also a cancer patient at the time of their death. The patient died today of Covid-19 pneumonitis.
“The third was a female resident of Elderly Residential Services, aged 90–95 years old, who died today from septicemia due to Covid-19.
“The fourth was a woman aged 95–100 years old, who died today of Covid-19 pneumonitis.”
The government continued to commend Covid vaccination, saying the vaccine’s rollout “brings us genuine relief and hope for a brighter tomorrow” and urged everyone to register their interest in being vaccinated.
VAERS lists the deaths of four elderly women that occurred in Kentucky nursing homes on the same day within hours of the women receiving the Pfizer-BioNTech vaccine.
Another VAERS report relates to the death on January 13 in Arizona of an 88-year-old woman who had arthritis and high blood pressure. She died the day after she received the Pfizer-BioNTech vaccine. The report states that the woman suffered initial pain in the back of her head, then “extreme headache” and vomiting. The report continued “At emergency, went into coma and was intubated. Hole drilled in skull to relieve pressure. MRI taken. Lot of bleeding in brain …” An aneurism led to the woman’s death approximately 14 hours after her initial symptoms.
Another report relates to the death of a 28-year-old man with no pre-existing conditions or listed medications, who was “found unresponsive at work” in New Jersey 19 days after receiving a first dose of the Pfizer-BioNTech vaccine. It was the day he was due to receive his second dose. He died on January 11, 2021, after being intubated and suffering cardiac arrest.
Another relates to the death of an 88-year-old man in Florida who had no pre-existing conditions and had an adverse reaction on the day he received the Pfizer-BioNTech vaccine (January 16).
The report states that, within five to ten seconds after vaccination, the man patient started clenching his hands tightly and became unresponsive. He was lowered to the floor and did not exhibit a pulse.
“CPR was initiated and 911 was called,” the report continued. “An AED [automated external defibrillator] was used and healthcare professionals onsite continued compressions until the paramedics arrived.”
Another elderly man in Florida (aged 75). “became sick three hours after the vaccine and was found deceased one day after his vaccination”.
Arutz Sheva (Israel National News), reported that a 75-year-old man from Beit Shean died from cardiac arrest on December 28 about two hours after being vaccinated with the Pfizer-BioNTech vaccine. Israel’s health ministry said initial investigation of the case showed no link between the man’s death and his vaccination.
The man received the vaccine at 8:30 a.m, and waited for the customary time at the health clinic before he was released to his home feeling well, Arutz Sheva reported, adding that, some time later, the man lost consciousness and was later confirmed dead from heart failure.
Arutz Sheva quoted the health ministry as saying the man suffered from heart disease and had had several heart attacks.
The publication also reported on the death of an 88-year-old man who collapsed in his home on December 29 a few hours after receiving a Covid vaccination and died later in hospital.
The man “suffered from prolonged, complex, and severe background illnesses”, Arutz Sheva quoted a hospital spokesperson as saying.
In an article published in The BMJ on January 15, Ingrid Torjesen reports that doctors in Norway have been told to conduct more thorough evaluations of very frail elderly patients in line to receive the Pfizer-BioNTech vaccine following the deaths of 23 patients shortly after receiving the vaccine.
Torjesen quotes the medical director of the Norwegian Medicines Agency (NOMA), Steinar Madsen, as saying: “It may be a coincidence, but we aren’t sure. There is no certain connection between these deaths and the vaccine.”
The agency has investigated 13 of the deaths so far and concluded that common adverse reactions of mRNA vaccines, such as fever, nausea, and diarrhoea, may have contributed to fatal outcomes in some of the frail patients, Torjesen reported.
“There is a possibility that these common adverse reactions, that are not dangerous in fitter, younger patients and are not unusual with vaccines, may aggravate underlying disease in the elderly,” Torjesen quotes Madsen as saying.
“We are now asking for doctors to continue with the vaccination, but to carry out extra evaluation of very sick people whose underlying condition might be aggravated by it,” Madsen is further quoted as saying.
This evaluation includes discussing the risks and benefits of vaccination with the patient and their families to decide whether or not vaccination is the best course, Torjesen wrote.
Pfizer said that Pfizer and BioNTech were working with NOMA to gather all the relevant information and all reported deaths would be thoroughly evaluated by NOMA to determine if they were related to the vaccine.
“The Norwegian government will also consider adjusting their vaccination instructions to take the patients’ health into more consideration,” Pfizer added.
In the briefing document the FDA released on December 8 it reports that two trial participants who received the Pfizer-BioNTech vaccine died. They were both more than 55 years of age.
The document was released ahead of the Vaccines and Related Biological Products Advisory Committee Meeting held on December 10.
It states: “A total of six (two vaccine, four placebo) of 43,448 enrolled participants (0.01%) died during the reporting period from April 29, 2020 (first participant, first visit) to November 14, 2020 (cutoff date). Both vaccine recipients were >55 years of age; one experienced a cardiac arrest 62 days after vaccination #2 and died three days later, and the other died from arteriosclerosis three days after vaccination #1.
“The placebo recipients died from myocardial infarction (n=1), hemorrhagic stroke (n=1) or unknown causes (n=2); three of the four deaths occurred in the older group (>55 years of age). All deaths represent events that occur in the general population of the age groups where they occurred, at a similar rate.”
Adverse reaction reports from Australia
In its safety report about Covid vaccination published on September 23, 2022, the TGA said that, as of September 18, 2022, it had received 136,191 reports of adverse reactions after Covid vaccination.
The TGA noted that, as of September 14, 63,342,668 Covid vaccine doses had been administered in Australia.
The administration said that, as of September 18, it had received 939 reports of people dying after Covid vaccination.
The TGA now says that in the case of 14 of the 939 deaths “the cause of death was linked to vaccination”.
Thirteen of the deaths occurred after a first dose of the AstraZeneca-Oxford vaccine, now branded as Vaxzevria in Australia, and one after a booster dose of the Moderna vaccine, now branded as Spikevax in Autralia.
The woman who died a few weeks after receiving the Moderna booster was 21 years old. The adverse event report was made on April 12, 2022.
The TGA states in its most recent summary that an external expert Vaccine Safety Investigation Group (VSIG) was convened on September 7, 2022, to consider whether any additional advice to the general public and healthcare professionals was required after the woman’s death.
“The panel agreed with the TGA’s assessment that the myocarditis the woman experienced was likely to have been related to vaccination given the available information, including the absence of other apparent causes of the myocarditis, and the timeframe for the onset of symptoms,” the TGA said.
“However, the panel acknowledged there were several other complicating factors that may have contributed to her death.”
The panel recommended that the existing warning about myocarditis be strengthened in the prescribing information for Comirnaty and Spikevax. and referred the case to the Australian Technical Advisory Group on Immunisation (ATAGI), which is publishing an update to clinical guidance for healthcare professionals about myocarditis and pericarditis after Covid-19 vaccination.
The TGA said the circumstances and potential causes that led to the woman’s death would be officially investigated by a state coroner.
Myocarditis was just one of a long list of adverse reactions reported in the woman’s case.
The TGA said in its latest summary: “As myocarditis is more commonly seen in males aged 12–30 years after a second vaccine dose, the expert panel noted there may be less awareness in the community that myocarditis can also occur in women and after a booster vaccine dose.
“This highlights the importance of informing patients, whether male or female, about the risk of myocarditis before receiving a vaccine dose and ensuring health professionals consider the possibility of myocarditis when patients present with new symptoms following vaccination.”
Eight of the 14 deaths that the TGA accepts were linked to Covid vaccination were cases of thrombosis with thrombocytopenia syndrome (TTS), two were linked to Guillain-Barré syndrome, and one was a case of immune thrombocytopenia. Six of those who died from TTS were women.
In the September 23 summary, the TGA doesn’t give details about the other two deaths and states only that they were “related to very rare conditions involving the nervous system”.
The administration said in a previous safety report: “A Vaccine Safety Investigation Group [VSIG] met on 10 June 2022 and classified two more deaths as likely linked to vaccination. Both were following a first dose of Vaxzevria (AstraZeneca) and were related to very rare conditions involving the nervous system.”
The administration added: “After close consideration, the expert group agreed that these extremely rare and unusual conditions were most likely related to vaccination based on the lack of evidence for alternative causes and the short period between vaccination and symptom onset.”
The TGA said that the two men, who were from Victoria, died within two months of receiving their first dose of Vaxzevria. Both deaths occurred in mid-2021.
One of the men who died was 72 years old. He initially experienced symptoms, including muscle weakness, suggestive of Guillain-Barre Syndrome approximately two weeks after vaccination, the TGA said. His condition worsened and he died six weeks later.
“Further clinical investigation found that the man experienced a rare and severe form of nerve damage, related to GBS, together with another neurological condition related to transverse myelitis,” the TGA said.
“GBS and transverse myelitis are known, very rare adverse events for Vaxzevria (AstraZeneca). These events were previously identified by the TGA and international regulators, leading to their inclusion in the product information. The VSIG agreed that the relatively short time between vaccination and his symptom onset, the unusual nature of the condition and lack of an alternate cause suggested vaccination was the likely cause of these conditions.”
The TGA noted that there was some information missing, including whether the man had tested positive for Covid-19.
The second man who died was aged 63 years. He developed acute disseminated encephalomyelitis (ADEM) 12 days after vaccination and died from the condition two weeks later.
ADEM is a neurological, immune-mediated disorder in which widespread inflammation of the brain and spinal cord damages tissue known as white matter. White matter is tissue composed of nerve fibres, many of which are covered by a collection of fats and proteins known as myelin.
Damage to the myelin sheath (demyelination) affects the nerve’s ability to transmit information and potentially can cause a wide range of neurological symptoms.
“Following review of the available clinical information, the VSIG advised that vaccination was the likely cause of ADEM in this individual given the lack of evidence for alternative causes and the short period between vaccination and symptom onset,” the TGA said.
“However, all other potential causes could not be excluded on the information available to the group, including whether the individual had tested positive for Covid-19.”
The TGA says in its most recent summary that, in Section 4.4 of the product information for Vaxzevria, an existing warning about very rare demyelinating disorders had been updated to include acute disseminated encephalomyelitis.
The warning reads: “Very rare events of demyelinating disorders, including acute disseminated encephalomyelitis, have been reported following vaccination with Vaxzevria.
“A causal relationship has not been established. Healthcare professionals should be alert of signs and symptoms of demyelinating disorders to ensure correct diagnosis, in order to initiate adequate supportive care and treatment, and to rule out other causes.”
Cutaneous vasculitis has also been added to Section 4.8 of the product information “as a rare skin disorder that has been reported after vaccination”.
The administration said in an earlier report that the two fatal cases of GBS after the administration of Vaxzevria were considered by the VSIG, which is made up of clinical experts and consumer representatives, on December 7.
“The group determined that both cases were consistent with being caused by vaccination,” the TGA said.
The people who died were a 77-year-old woman from Victoria and an 81-year-old woman from New South Wales.
The TGA said that information considered for two fatal cases of an unusual form of myocarditis in people over 50 years old and one suspected case of multisystem inflammatory syndrome after the administration of the Pfizer-BioNTech (Comirnaty) vaccine “did not support the events as being related to vaccination”.
The administration said that, in the suspected case of multisystem inflammatory syndrome, there was not enough medical information to determine if it was related to the vaccine.
“While the symptoms started near to the time of vaccination, there was insufficient information to diagnose multisystem inflammatory syndrome and establish a possible link to vaccination,” the TGA said.
One of the post-vaccination deaths from TTS was that of a 72-year-old woman from South Australia whose death was confirmed on July 12, 2021. She had a very severe case of TTS involving blood clots in her brain and a very low platelet count.
It was reported that the woman received her first dose of Vaxzevria on June 24, 2021, and was admitted to hospital on July 5.
The woman who died from ITP was 61 years old and had received a first dose of Vaxzevria. The VSIG, convened by the TGA on July 2, said that a “very rare but fatal case of immune thrombocytopenia” was “likely linked to the vaccine”.
The TGA said: “This was based on the lack of strong evidence for other causes and the occurrence of the event being within a plausible time period after vaccination. While the woman had experienced a recent viral illness that could have theoretically caused ITP, the panel felt that the unusual severity of the event suggested that vaccination was a more likely cause.”
ITP, in which a person’s immune system mistakenly destroys platelets, which help blood to clot, can occur after the immune system is activated, for example by a viral infection or vaccination and has been reported after vaccination for hepatitis B, measles, mumps, rubella, and influenza.
The TGA said that the 14 deaths it considered likely to be related to vaccination occurred in people aged 21–81 years.
According to worldometers.info, as of September 26, 2022, there had been 14,928 recorded deaths from Covid-19 in Australia.
As of September 11, the total number given on the TGA’s public Database of Adverse Event Notifications (DAEN) of deaths after Covid vaccination (all vaccines) was 937, but only three of those fatalities were specifically referred to as deaths in the ‘Medicine summary’.
A total 196 of the deaths are referred to as an ‘adverse event following immunisation’ in the category ‘Injury, poisoning and procedural complications’. Finding specific details about the other deaths is hampered by the continual malfunctioning of certain advanced search options.
In a previous safety summary, the TGA reported on the outcomes of a vaccine safety investigation group meeting held on May 6, 2022.
“The TGA convened an external expert group to review the death of an Aboriginal woman in her 50s who developed myocarditis 33 days after receiving a third dose of the Comirnaty (Pfizer) vaccine,” the TGA said.
The group included a panel of experts in cardiology, infectious diseases and vaccines, rheumatology, intensive care, and communication along with a consumer representative and an Aboriginal health advisor.
“After carefully reviewing the details of the medical history and medical events leading to this death, the panel concluded it was unlikely to be caused by the Comirnaty (Pfizer) vaccine,” the TGA reported.
“This was for several reasons, including that the symptoms developed a long time after the time that we usually expect to see myocarditis from a vaccine – which is about one– five days after vaccination.
“This accepted timeframe is based on accumulated evidence from Australian and international cases of myocarditis caused by vaccination. The panel agreed that in this case myocarditis was likely due to other causes rather than vaccination.”
The TGA said in an earlier report that safety monitoring had not identified any additional or specific risks with the Covid-19 vaccines in Aboriginal and Torres Strait Islander people compared to the overall Australian population.
“The reporting rate of adverse events is slightly lower for Aboriginal and Torres Strait Islander people – at 1.4 reports per 1,000 vaccine doses – but the type and frequency of adverse effects are very similar,” the administration said.
The TGA also said in a previous safety report that more than 75% of the 705 people who had died after Covid vaccination as of December 12, 2021, were aged 65 years and older and the median age was 76 years.
“A very small number of deaths have been reported in individuals under 35 years of age, including two adolescents. Only one death reported in a younger person has been linked to vaccination – this was in a 34-year-old woman who died as a result of TTS,” the TGA said on December 16.
The TGA said in an earlier report that the two fatal cases of GBS after the administration of Vaxzevria were considered by the VSIG, which is made up of clinical experts and consumer representatives, on December 7.
“The group determined that both cases were consistent with being caused by vaccination,” the TGA said.
The people who died were a 77-year-old woman from Victoria and an 81-year-old woman from New South Wales.
The TGA said that information considered for two fatal cases of an unusual form of myocarditis in people over 50 years old and one suspected case of multisystem inflammatory syndrome after the administration of the Pfizer-BioNTech (Comirnaty) vaccine “did not support the events as being related to vaccination”.
The administration said that, in the suspected case of multisystem inflammatory syndrome, there was not enough medical information to determine if it was related to the vaccine.
“While the symptoms started near to the time of vaccination, there was insufficient information to diagnose multisystem inflammatory syndrome and establish a possible link to vaccination,” the TGA said.
One of the post-vaccination deaths from TTS was that of a 72-year-old woman from South Australia whose death was confirmed on July 12, 2021. She had a very severe case of TTS involving blood clots in her brain and a very low platelet count.
It was reported that the woman received her first dose of Vaxzevria on June 24, 2021, and was admitted to hospital on July 5.
The woman who died from ITP was 61 years old and had received a first dose of Vaxzevria. The VSIG, convened by the TGA on July 2, said that a “very rare but fatal case of immune thrombocytopenia” was “likely linked to the vaccine”.
The TGA said: “This was based on the lack of strong evidence for other causes and the occurrence of the event being within a plausible time period after vaccination. While the woman had experienced a recent viral illness that could have theoretically caused ITP, the panel felt that the unusual severity of the event suggested that vaccination was a more likely cause.”
ITP, in which a person’s immune system mistakenly destroys platelets, which help blood to clot, can occur after the immune system is activated, for example by a viral infection or vaccination and has been reported after vaccination for hepatitis B, measles, mumps, rubella, and influenza.
The TGA says in its latest safety report that there has been no change in the reporting rates for ITP, GBS, or TTS after Covid vaccination in 2022, but that it that it continues to monitor for reports “to identify new information about these risks”.
The administration said in a previous summary that, as of March 13, it had received 87 reports of suspected ITP, two of which were reported in 2022 but had a vaccination date in 2021.
The TGA said in an earlier report that, as of January 23, 2022, it had received 86 reports of suspected ITP after the administration of Vaxzevria.
“These patients had an extremely low platelet count, and signs of thrombocytopenia which may include unusual bruising, a nosebleed, and/or blood blisters in the mouth,” the TGA said.
“Their symptoms occurred in a timeframe that suggested they could be linked to vaccination and no other obvious cause was identified based on the information provided to the TGA.”
In Australia, the TGA says, ITP after Covid-19 vaccination is very rare. ITP had been reported in about one in every 100,000 people who received Vaxzevria, the administration said.
The TGA added that, following an investigation by the TGA, the product information for Vaxzevria had been updated to include a warning about ITP.
The administration said in a previous report: “Amendments to the wording about thrombocytopenia have also been made to the PI [product information] under Coagulation disorders in section 4.4.
“This includes the following warning: ‘If an individual has a history of a thrombocytopenic disorder, such as ITP, the risk of developing low platelet levels should be considered before administering the vaccine and platelet monitoring is recommended after vaccination’.”
The TGA had said in an earlier safety report: “Apart from one previously reported fatal case that was assessed by an expert Vaccine Safety Investigation Group as being likely to be vaccine related, other suspected cases of ITP have not been definitively linked to vaccination.”
Vaccinating children and adolescents
The TGA said it was closely monitoring adverse event reports relating to 12- to 17-year-olds and that, as of September 18, it had received about 4,280 such reports after about 3.7 million doses of Comirnaty and Spikevax had been administered to children and adolescents in the age group.
The most commonly reported reactions were chest pain, headache, dizziness, nausea, and fever, the TGA said.
The administration added that, as of September 18, it had received about 1,630 reports of adverse reactions in five-to 11-year-olds after the administration of approximately 2.3 million Comirnaty and Spikevax doses to children in this age group.
The most common reactions reported included chest pain, vomiting, fever, headaches, and abdominal pain, the TGA said.
There are four cases listed on the DAEN of children dying after they were vaccinated with Comirnaty. One of the cases is that of a seven-year-old boy who is reported to have suffered a cardiac arrest and a generalised tonic-clonic seizure. The second is the case of a nine-year-old girl who is also reported to have suffered a heart attack. The third death – that of a ten-year-old boy – is simply referred to as an ‘adverse event following immunisation’. In the case of the fourth death the five-year-old boy is reported to have suffered a cardiac arrest and abdominal pain. A fifth case – that of a six-year-old boy about whose death no details were given – is no longer listed. This fatality had previously been referred to as an ‘adverse event following immunisation’. (There is further information about these cases in the ‘DAEN reports’ section below.)
The TGA doesn’t mention the four deaths in its latest safety report and reasserts: “There have been no deaths in children or adolescents determined to be linked to COVID-19 vaccination.”
As of September 18, about 2.3 million doses of Comirnaty and Spikevax had been administered to children aged five to 11 years, or six to 11 years in the case of Spikevax, the administration added.
In Australia, Comirnaty is the only Covid-19 vaccine approved for administration to five-year-olds. No Covid-19 vaccines are approved in Australia for children aged four years of age and below.
The TGA said earlier that it had received 42 reports of vaccination errors in 5- to 11-year-olds.
“Most of these are dosing errors in children aged 10 or 11 years old who received an adult dose of the vaccine by mistake, but there are also a few reports in younger children,” the TGA said.
In the majority of the reports, no adverse events were associated with receiving an incorrect dose, the agency said. “However, four reports contained an adverse event – these were common and expected reactions including fever, headache and injection-site reactions,” the administration added.
The paediatric version of Comirnaty is specifically formulated for 5- to 11-year-olds and comes in a vial with an orange top. Formulations for adolescents and adults have a purple or grey top and need to be diluted differently before use.
There is not a separate paediatric formulation of Spikevax. For the six- to 11-year age group, the dose is half that used for the primary vaccine course in older children and adolescents and adults.
In its most recent summary, the TGA doesn’t give any data about adverse reactions to vaccination in the under-five age group and simply states that it be “closely monitoring reports of adverse events in younger children”.
Approximately 14.2 million people had received boosters in Australia as of September 18, the TGA said in its latest safety report. This included 4.8 million people who had received a fourth dose.
“We have received approximately 9,550 reports of suspected adverse events identified as occurring after a booster dose,” the TGA said. “These reports do not suggest any emerging safety concerns with a booster dose that are different to the first and second vaccine doses.”
The administration said the reports of suspected adverse events included “a small number” of cases of myocarditis and pericarditis.
The administration said in a previous report: “Although data is very limited at this point, rates of reporting for adverse events of special interest such as myocarditis, pericarditis and anaphylaxis appear to be lower following booster doses.”Comirnaty and Spikevax are approved for administration as booster doses in Australia (Comirnaty is recommended as a booster for people aged 16 years and above and Spikevax is recommended for those aged 18 years and above). On February 8, 2022, the TGA provisionally approved the use of Vaxzevria as a booster for people aged 18 years and older.
“The third (booster) dose may be given if clinically indicated with reference to official guidance regarding the use of a heterologous third dose (e.g. mRNA vaccine),” the TGA said.
“This means that the decision to receive Vaxzevria as a booster must be made in consultation with a medical professional. The mRNA Covid-19 vaccines (Comirnaty (Pfizer) or Spikevax (Moderna) are preferred as the booster dose in Australia, irrespective of the primary Covid-19 vaccine used. This includes for people who received the AstraZeneca Covid-19 vaccine for their primary course.”
For people who are immunocompromised, a third dose is given as part of their primary vaccine course. This is not considered to be a booster.
The TGA notes that, in Australia, a booster dose is most commonly a third dose of an mRNA vaccine.
It adds that a fourth dose has been recommended for people over 65 years of age, and a “winter booster dose” was also now recommended for people aged 16–64 years who have a medical condition that increases their risk of severe Covid-19 illness or a disability “with significant or complex health needs or multiple comorbidities that increase the risk of poor outcomes from Covid-19”.
The ATAGI has recommended that adolescents aged 12–15 years “who are at greater risk of severe disease from Covid-19 should be given a first booster dose of Comirnaty”, the TGA added.
The risk of myocarditis and/or pericarditis after the administration of Comirnaty and Spikevax was recognised, the TGA said.
“So far, reports of myocarditis after a booster dose are very rare, occurring in less than one in every 100,000 vaccinated people,” the administration added.
The TGA said that, as of September 18, it had received 59 reports of likely myocarditis and 98 reports of likely pericarditis when the booster dose was Comirnaty.
There had also been 26 reports of likely myocarditis and 25 reports of likely pericarditis when the booster dose was Spikevax.
The median age of those affected was 33 years, the TGA said.
The TGA said in an earlier report: “Myocarditis following Covid-19 vaccination is most likely to be reported in adolescents and young men, whereas the median age of people who have received a third or booster dose of a Covid-19 vaccine to date is 52 years.”
“The TGA will continue to closely monitor myocarditis and pericarditis following booster or third doses as the booster rollout extends to younger age groups.”
The TGA also said earlier that it was closely monitoring myocarditis and pericarditis with different vaccine combinations for first and second doses and boosters.
“At this point, although we have only a small number of reports of pericarditis and/or myocarditis, we have not seen any patterns or trends in the data to indicate any difference with mixed vaccine combinations,” the administration said in an earlier report.
The TGA said in the September 18 summary that the most common adverse events reported to the administration following a booster dose were headaches, swollen lymph nodes (also called lymphadenopathy), chest pain, muscle pain, and fever.
It said that swollen lymph nodes were “a normal and known side effect of vaccines” and occurred when the immune system was stimulated.
“Swollen lymph nodes were observed in the clinical trials,” the administration said in a previous report. “For Comirnaty (Pfizer), this occurred more frequently after a third or booster dose (5% of people) than after the first or second doses (less than 1% of people) in the clinical trials. For Spikevax (Moderna), this occurred in up to 10% of people.”
Myocarditis and pericarditis
The TGA said that, as of September 18, it had received 1,424 reports of suspected myocarditis (alone or along with pericarditis) after the administration of Comirnaty, including 230 cases in 12- to 17-year-olds.
The administration added that it had received 2,814 reports of suspected pericarditis after the administration of Comirnaty, including 182 cases in 12- to 17-year-olds.
The TGA added that it had received 39 reports of suspected myocarditis and/or pericarditis in five- to 11-year-olds. “Following review of the reports, four were likely to represent myocarditis and another seven reports were likely to represent pericarditis,” the TGA said.
There were 3,030 cases of pericarditis after the administration of Comirnaty listed on the DAEN as of September 11.
The TGA said it had received 712 reports after administration of Comirnaty that had been assessed as likely to be myocarditis. A total 168 of these reports related to 12- to 17-year-olds.
The administration also said that 33 of the 198 reports of suspected myocarditis alone or in combination with pericarditis after administration of the Moderna vaccine were in 12- to 17-year-olds.
A total 297 suspected cases of pericarditis had been reported after administration of the Moderna vaccine and 13 of these cases were in 12- to 17-year-olds, the TGA said. The administration had previously reported that, in one of these cases, the patient was a boy aged 12 years. In two of the cases, the patients were 16-year-old boys.
The TGA said it had received 113 reports after administration of the Moderna vaccine that had been assessed as likely to be myocarditis. Twenty-six of these reports related to 12- to 17-year-olds.
The TGA said in a previous report: “The number of reports of myocarditis is increasing each week, which is expected as the number of vaccine doses given also increases each week.“While there are some fluctuations from week to week, especially in subgroups with small numbers of reports, rates of reporting of myocarditis in Australia are consistent with rates reported internationally.”
The administration had also said earlier: “Like other countries, we have observed a higher-than-expected number of cases of myocarditis in vaccinated compared to unvaccinated individuals for Comirnaty (Pfizer).”
The TGA said in the September 23 summary: “Myocarditis is reported in around 1–2 in every 100,000 people who receive Comirnaty (Pfizer) and around two in every 100,000 of those who receive Spikevax (Moderna).
“It occurs in males and females but is more common after the second dose in boys aged 12–17 years (13 cases per 100,000 Comirnaty doses and 24 cases per 100,000 Spikevax doses) and men under 30 (nine cases per 100,000 Comirnaty doses and 23 cases per 100,000 Spikevax doses).”
The youngest person whose condition after Covid-19 vaccination was classified as “likely myocarditis” is six years old.
The administration added: “Pericarditis is reported in about two in every 100,000 people who receive an mRNA vaccine. It is reported more often after the Nuvaxovid (Novavax) vaccine, with about 12 reports for every 100,000 doses administered, most commonly in males aged 18-49 years old. The pericarditis rate for Nuvaxovid is less certain than for Comirnaty and Spikevax due to the low numbers of Nuvaxovid vaccine doses given.”
The TGA said that the number of reports of suspected myocarditis and/or pericarditis in people who had received the Nuvaxovid vaccine was small.
“After assessing these against a set of internationally accepted criteria, nine cases were likely to represent myocarditis and 27 were likely to represent pericarditis,” the administration said.
“As a result of our investigation, the product information for Nuvaxovid (Novavax) has been updated to include pericarditis as a potential adverse event.”
The administration had said earlier that, in Australia, the rates of pericarditis were similar between the mRNA vaccines.
“Emerging Australian and international data indicate that pericarditis is more common in people under 50 years of age than in older people,” the administration added. The TGA said in an earlier report that there was a trend to a higher rate in the 18- to 39-year-old group.
The TGA said anaphylaxis, paraesthesia, and hypoaesthesia had also been added to the Nuvaxovid product information as potential adverse events.
“These adverse events are also recognised for other Covid-19 vaccines in use in Australia,” the administration added.
There are reports of 33 cases of pericarditis, ten cases of myocarditis, and one case of myopericarditis listed on the DAEN that occurred after the administration of Nuvaxovid.
The TGA said that, as of September 18, about 217,000 doses of Nuvaxovid had been administered in Australia.
The administration noted that, as of September 18, about 44 million doses of Comirnaty had been administered in Australia.
The administration said in a previous report: “In some countries, higher rates of myocarditis and pericarditis have been reported with Spikevax (Moderna) than with Comirnaty (Pfizer).
“In Australia, slightly higher estimated rates of myocarditis for Spikevax –1.6 cases per 100,000 Spikevax doses versus 1.3 cases per 100,000 Comirnaty doses. This difference is smaller than that reported overseas, including in the UK and Canada.”
The administration had said earlier that it was not seeing a difference in age-specific rates between the vaccines, although the numbers of cases reported within age groups for Spikevax were low.
The TGA had also said in an earlier report: “Because the number of cases of myocarditis reported after Spikevax (Moderna) in Australia is small, at this stage we are not able to calculate reliable reporting rates for it or to see any difference in risk between the two vaccines.”
The ATAGI advises that people who develop myocarditis attributed to their first vaccine dose should defer further doses of an mRNA Covid-19 vaccine and discuss this with their treating doctor.
For those with suspected pericarditis after a first dose, future dose recommendations depend on test results and the person’s age and sex, the TGA says.
The administration said its analysis indicated that most patients with likely myocarditis experienced symptoms within three days of vaccination.
The TGA said in its safety report published on December 9 that it had not identified any vaccine-related deaths from myocarditis in Australia.
Based on the available information, and after review by the VSIG, two fatal cases of myocarditis were not found to be related to vaccination, the administration said.
Both cases occurred after a first dose of Comirnaty, the TGA said. One of the deaths was of a 52-year-old man from New South Wales and the other was of a 60-year- old woman from Queensland.
Both people had signs of giant cell myocarditis, the TGA said. “In one case myocarditis occurred soon after vaccination, but the individual also had an underlying medical condition that could have caused symptoms,” the administration added.
“The timeframe of the second case, together with the clinical features, suggested myocarditis was not related to vaccination and was more likely to be due to other causes.”
The TGA doesn’t mention this in its safety report, but there were, as of September 11, 76 cases of myocarditis and 209 cases of pericarditis listed on the DAEN after the administration of Vaxzevria. Two of the cases of myocarditis are listed as having been fatal.
Thrombosis with thrombocytopenia syndrome
The TGA said it had received 173 reports of cases of TTS after the administration of Vaxzevria.
Of these cases, 149 (83 confirmed and 66 probable) followed a first dose of the vaccine and 24 (five confirmed and 19 probable) followed a second dose, the TGA said.
“With only limited use of the Vaxzevria (AstraZeneca) vaccine now in Australia, we have not received any new reports of confirmed or probable TTS this year,” the TGA said.
The administration said that, as of September 18, 2022, about 13.8 million doses of Vaxzevria had been administered in Australia. “However, since the end of 2021 very few doses are being used,” the TGA added.
The TGA said in a previous safety report that new information on the case of a 20-year-old woman from Queensland, reported in late 2021, indicated that it did fit the criteria of probable TTS related to a second dose of Vaxzevria.
The TGA said in a previous report that, on January 21, 2022, a Vaccine Safety Investigation Group assessed two fatal cases of suspected TTS following a second dose of Vaxzevria. Both of the people who died were aged 60 years or more.
In one case, the person’s symptoms developed after the usual window for TTS (which is 4-30 days following vaccination), the TGA said.
“After reviewing the available information, the panel concluded that this case was inconsistent with vaccine-related TTS and was more likely to be a result of the patient’s other conditions,” the administration added.
“For the other case, although the person’s symptoms developed in a timeframe that suggested they could have been related to vaccination, the patient had an underlying condition that was more likely to have contributed to the symptoms. It was considered that there was insufficient evidence to indicate a link.”
The TGA said that, in Australia, TTS was reported in about two in every 100,000 vaccinated people following the first dose of Vaxzevria and 0.3 in every 100,000 vaccinated people after the second dose.
The administration had said previously that, when assessed against the criteria used by the CDC in the US, about one third of the TTS cases reported to the TGA after a first dose were classified as Tier 1 cases, which tend to have more serious outcomes.The TGA said that younger women seemed to be slightly more likely to have serious outcomes from TTS as they more often experienced clots in unusual locations, such as the brain or abdomen.
“People under 60 years are more likely to be classified as Tier 1 and/or require treatment in intensive care,” the administration added.
The CDC defines a case as Tier 1 when there is blood clotting in an unusual location such as the brain or abdomen and there is a low platelet count with or without anti-PF4 antibodies. It defines a case as Tier 2 when there is blood clotting in common locations such as the leg or the lungs and a low platelet count and anti-PF4 antibodies.
Cases reported after a second vaccine dose were much less likely to be classified as Tier 1, the TGA said, and most of these cases occurred in people aged over 60 years.
In Australia, the TGA has said, the risk of dying from TTS after vaccination is about one in a million (people receiving a first dose).
The administration said in an earlier report: “Nearly half of the TTS cases in women required treatment in intensive care. Cases meeting the criteria for Tier 1 were 2.5 times more likely to occur in women compared to men.”
It also said earlier: “To date, the reporting rate of TTS remains higher in people aged under 60 years (2.5 per 100,000 doses) compared to those aged 60 and over (1.8 per 100,000 doses). However, we have not seen a rise in the incidence in younger people.”
The TGA says that, in Australia, TTS cases have most often occurred about two weeks after vaccination.
“To date, cases presenting with a longer time to onset (over fifty days) have been designated as probable cases and have presented with common forms of clots,” the administration said in an earlier safety report. “It can be difficult to distinguish between normal clots and TTS for these cases and they remain under investigation.”
The TGA said in an earlier report that, in about half of the Tier 1 TTS cases, the patients had clots in the brain (cerebral venous sinus thrombosis) and half had clots in the abdomen (splanchnic vein thrombosis).
“Of those with clots in the brain, around half also had another clot in the leg (deep vein thrombosis) or the lungs (pulmonary embolism),” the TGA added. “The Tier 2 and unclassified TTS cases had only the more common clots like deep vein thrombosis or pulmonary embolism.”
The TGA said in a previous report that several recent updates had been made to the Vaxzevria product information “under section 4.4 special warnings and precautions for use”. The updates are based on post-market monitoring and include the following:
- an updated warning about neurological events which specifically mentions GBS as a demyelinating disorder, and.
- a new statement under thrombosis and thrombocytopenia: “The reporting rates after the second dose are lower compared to after the first dose.”
The TGA said that a new warning for venous thromboembolic events without thrombocytopenia had been issued stating the following: “Venous thromboembolic events without accompanying thrombocytopenia, including events of cerebrovascular venous and sinus thrombosis (CVST) have been reported following vaccination with Vaxzevria.
“Although a causal relationship has not been established, these events can be fatal and may require different treatment approaches than TTS. Healthcare professionals should consult applicable guidance.”
The administration added that venous thromboembolic events included “common clots” such as those that develop in the legs and lungs (deep vein thrombosis and pulmonary embolism) as well as more serious clots that could form in the brain.
“A link between these clots and vaccination is not clear, except when they occur in people with thrombosis with thrombocytopenia syndrome (TTS) linked to the vaccine,” the TGA said.
The TGA said that, as of January 9, it had received 45 reports of CVST and other related events without thrombocytopenia in people who had received Vaxzevria.
The administration said in an earlier safety report that, as more was learnt about TTS internationally, it was considering modifying its case criteria to include, for example, the time to onset of symptoms as part of the criteria for confirming TTS.
“If the criteria are updated, it may result in some cases being reclassified as unlikely to be TTS because they present such a long time after vaccination and/or are likely to be due to other causes,” the TGA said.
The TGA also said in a previous safety report that most cases of TTS had occurred in people aged over 50 years because Vaxzevria had been used almost exclusively in that age group since the recommendation from the Australian Technical Advisory Group on Immunisation (ATAGI) on April 8 that the Pfizer-BioNTech vaccine was preferable for people aged under 50 years.
On June 17, 2021, the ATAGI recommended that the Pfizer-BioNTech vaccine be preferred over Vaxzevria for people aged 16 to under 60 years old.
Previously it had recommended Comirnaty in preference to Vaxzevria for those aged 16 to under 50 years old.
“ATAGI updated their recommendations due to emerging evidence in Australia of a higher risk and severity of TTS with the first AstraZeneca dose in the 50–59 year age group,” the TGA said.
The TGA said that people aged 50–59 years who had already received the first dose of Vaxzevria should complete their two-dose schedule.
On July 24, the ATAGI changed its message in specific reference to Sydney. It said it reaffirmed its previous advice that, in a large outbreak, the benefits of Vaxzevria were “greater than the risk of rare side effects for all age groups”.
The advisory group said: “All individuals aged 18 years and above in greater Sydney, including adults under 60 years of age, should strongly consider getting vaccinated with any available vaccine including Covid-19 Vaccine AstraZeneca.
“This is on the basis of the increasing risk of Covid-19 and ongoing constraints of Comirnaty (Pfizer) supplies. In addition, people in areas where outbreaks are occurring can receive the second dose of the AstraZeneca vaccine four to eight weeks after the first dose, rather than the usual 12 weeks, to bring forward optimal protection.”
In its report published on September 24, it reiterated this message, stating: “In areas with significant outbreaks including greater Sydney and Melbourne, all individuals aged 18 years and above should strongly consider getting vaccinated with any available vaccine including AstraZeneca.”
The ATAGI also said the benefits of vaccination with Vaxzevria in preventing severe Covid-19 “strongly outweigh the risks of adverse effects in all Australians 60 years and above”.
In a previous summary, it said that, as of March 13, it had received 160 reports of suspected GBS after the administration of Vaxzevria. Nine of these cases were reported in 2022, but six of them had a vaccination date in 2021, the TGA said.
The TGA said that while many cases of GBS resolved within months, recovery in some people could take years.The administration said that, in the case of the two fatal cases of GBS, the decision that they were likely to be related to vaccination was based on the time period between vaccination and GBS developing, the absence of other identifiable causes, and evidence from international investigations of a possible link between GBS and Vaxzevria.
“However, there was some uncertainty around this determination because GBS occurs in people who have not received a vaccine and sometimes there is no obvious trigger identified,” the TGA added in a previous report.
The TGA said that it was expected that some suspected cases of GBS might not be related to vaccination as GBS could occur after common viral infections and some types of gastroenteritis.
“We encourage people to seek medical attention if they experience symptoms that could suggest GBS as early medical care can reduce severity and improve outcomes,” the TGA said. “Symptoms to look out for include weakness, pain and paralysis in the hands or feet that can progress to the chest and face over a few days or weeks.”
In Australia, the TGA says, GBS has been reported in about one in every 100,000 people after the administration of Vaxzevria.
The administration added: “There is growing evidence of a possible link between GBS and Vaxzevria (AstraZeneca) following rigorous investigations of safety data by the TGA and other international regulators.
“This is reflected in recent updates to the Vaxzevria (AstraZeneca) product information.”
There were 85 cases of GBS listed on the DAEN as of September 11 that are reported to have occurred after the administration of Comirnaty.
The TGA said in a previous report that, as of March 13, it had received 19 reports of suspected transverse myelitis following the administration of Vaxzevria.
The administration added that the product information for Vaxzevria had been updated to include transverse myelitis as a potential adverse reaction.
“A warning about transverse myelitis has been included in the PI [product information] under sections 4.4 Special warnings and precautions for use and 4.8.
“This follows a review by the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee, which concluded there is a reasonable possibility of a causal link to the vaccine.”
The TGA also said in a previous report that, as of January 11, 2022, it had received approximately 11 reports of menstrual problems per 100,000 doses after the administration of Comirnaty in women aged under 50 years, 15 reports per 100,000 after the administration of Spikevax, and twenty reports per 100, 000 doses after the administration of Vaxzevria.
“These reporting rates have remained relatively stable over time,” the TGA said. “The most commonly reported symptoms include heavy periods, irregular, and delayed bleeding, and bleeding between periods.”
The TGA hasn’t, in its recent weekly safety reports, provided any detailed figures about reports of menstrual disorders or unexpected vaginal bleeding after Covid vaccination. As of September 11, 2022, there were more than 6,154 reports on the DAEN of menstrual disorders after Covid vaccination (all vaccines).
As of September 11, there were 146 reports on the DAEN of postmenopausal haemorrhage.
The TGA said in in a previous report that the product information for Vaxzevria had been updated to include the potential adverse events paraesthesia (an abnormal feeling in the skin, such as tingling or a crawling sensation), and hypoaesthesia, which is a decrease in normal sensation (numbness).
These events were not observed in the clinical trials but had been identified during post-market surveillance, the TGA said.
The TGA also said in a previous report that the product information for Comirnaty had been updated to include the potential adverse events erythema multiforme, paraesthesia, and hypoesthesia.
Again, the administration said the adverse events were not observed in the clinical trials but had been reported during post-market surveillance.
The adverse events had been reported to the TGA for each of the Covid-19 vaccines in use in Australia and were mentioned in about 9% of all reports relating to the Comirnaty (Pfizer) vaccine, the administration added.
Erythema multiforme usually resolved on its own, the TGA added, but treatment could be needed for more severe cases.
The agency said that, as of January 2, it had received five reports of suspected cases of erythema multiforme.
In a previous report the TGA said that, as of October 24, it had received 796 adverse event reports from Aboriginal and Torres Strait Islander people. “During this time approximately 629,000 vaccine doses have been given in this population, giving a reporting rate of 1.3 suspected adverse events per 1,000 doses,” the TGA said.
The TGA said in its report published on October 14 that it had received about 230 reports of asthenia (weakness) after the administration of Comirnaty along with 4,100 reports of lethargy, 230 reports of decreased appetite, and 580 reports of excessive sweating.
“These effects generally occurred within a day of vaccination when details were given. Lethargy was reported more often after the second vaccine dose,” the TGA said.
The administration noted that weakness, lack of energy, or sleepiness (lethargy), decreased appetite, and night sweats were added to the product information for Comirnaty in July 2021.
“Recently, the European Medicines Agency’s Pharmacovigilance Risk Assessment Committee also recommended that these adverse events should be listed as side effects in the European prescribing information for Comirnaty (Pfizer),” the TGA added.
The TGA also said in an earlier summary that it had received more reports of enlarged lymph nodes after the administration of Comirnaty than after the administration of Vaxzevria – approximately 17 reports per 100,000 doses after the former compared with six reports per 100,000 doses after the latter.
“An investigation by our scientific and clinical staff at the TGA found that the majority of these reports were in younger people most likely reflecting the higher use of Comirnaty (Pfizer) in younger age groups,” the TGA said.
The TGA says that swollen lymph nodes usually develop within a few days after Covid vaccination and resolve without treatment after a week or so.
“Changes in lymph nodes can also be a sign of other medical issues and there is concern that false readings on mammograms following vaccination could lead to additional unnecessary testing,” the TGA added.
“After considering the risks of postponing breast screening, the Royal Australian and New Zealand College of Radiologists recommends that breast screening should not be delayed following Covid-19 vaccination, particularly for women at higher risk of breast cancer and those living in rural and remote regions, where access to screening may be limited.”
A warning about lymphadenopathy is included in the product information for Comirnaty and Vaxzevria.
The TGA also noted in a previous summary that a warning about anxiety-related reactions following vaccination had been added to the product information for Vaxzevria.
“Reactions such as fainting or feeling faint, hyperventilation or stress-related events may occur in response to the needle injection or with the process of vaccination itself,” the TGA said.
“Stress-related reactions are not unique to Covid-19 vaccination and can occur with any procedure involving a needle. It is important that precautions are in place to avoid injury from fainting.”
The TGA noted in a previous summary that a warning about fainting following vaccination has been added to the product information for the Pfizer-BioNTech vaccine, stating that syncope may occur “in association with administration of injectable vaccines” and “procedures should be in place to avoid injury from fainting”.
The administration added: “Examination of the medical literature found that stress-related reactions to immunisation can be more common in younger people. Published evidence also suggests that giving immunisations in a mass vaccination centre can be a contributing factor, particularly when there is a cluster of anxiety-related reactions reported.”
In its summary published on June 10, the TGA focused on reports of herpes zoster reactivation (shingles) following Covid-19 vaccination.
The administration said that, as of June 6, it had received 99 reports of herpes zoster after administration of Vaxzevria and 43 reports after administration of Comirnaty. “For both vaccines, the majority of these reports were in the 45–64 year age group and 70% were reported in women,” the TGA said.
The administration added: “A preliminary review by the TGA indicates that the number of reports of shingles in vaccinated individuals is actually lower than the expected background rate of herpes zoster in Australia overall. Therefore, there does not seem to be a safety signal suggesting that shingles is a result of vaccination.”
On July 1, the TGA said it had been advised by the MHRA of the death of a woman in the UK five weeks after she received her first dose of Vaxzevria in Australia. The UK authorities ordered a postmortem.
“At that time, we advised that she had another serious underlying health condition,” the TGA said in an earlier summary. “Information received subsequently indicates that she did not in fact have an underlying condition.”
The TGA earlier reported on the case of a 78-year-old man who died from multi-organ failure after receiving Vaxzevria . He had signs of capillary leakage.
“Although there was a temporal link with the vaccine, an expert Vaccine Safety Investigation Group was unable to establish a causal link as other causes could not be ruled out,” the TGA said. “The TGA is in discussions with the sponsor about including information on capillary leak syndrome in the product information as a precautionary measure.”
The VSIG has also investigated the case of a 55-year-old-man who died eight days after receiving Vaxzevria.
The patient had pulmonary embolism (blood clots in his lungs) and evidence from a platelet functional assay suggesting that there were antibodies that activate platelets in the blood (anti-PF4 antibodies).
However, the TGA said, the patient did not have thrombocytopenia so did not meet the diagnostic criteria for TTS currently being used by the TGA and globally.
The TGA said the expert group could not conclusively determine if the patient’s death was related to the vaccine, in particular because of the absence of thrombocytopenia.
“However, it advised that the current criteria for the diagnosis of TTS are likely to evolve as we find out more about this rare condition,” the TGA said. “If the case definition for TTS changes, this case will be re-evaluated at a later date.”
Freedom of Information disclosure
On July 22, 2022, the TGA released a document under the Freedom of Information Act entitled ‘Annexed table from periodic Safety Update Report – BNT162b2 (COMIRNATY) – COVID-19 vaccine for reporting period 16 February 2022 to 15 April 2022’.
The document states that the cumulative number of adverse event cases reported globally from the start of vaccination with the Pfizer-BioNTech vaccine (BNT162b2) to April 15, 2022, totals 1,348,079 and the number of individual adverse events totals 4,563,770.
The number of reports of deaths (listed under ‘General disorders and administration site conditions’) is put at 2,894 (0.21 % of the reports).
There are also 679 reports of ‘sudden death’ listed, along with 147 reports of foetal death, 107 reports of ‘sudden cardiac death’, 76 reports of ‘cardiac death’, 47 reports of ‘brain death’, 40 reports of ‘cell death’, six reports of ‘neonatal death’, four reports of the death of a premature baby, three reports of ‘sudden infant death syndrome’, one report termed as ‘clinical death’, one report termed as ‘apparent death’, and one termed as ‘sudden unexplained death in epilepsy’.
Countries with the highest incidence of reports:
There are 11,299 reports of myocarditis, along with 44 reports of viral myocarditis, seven reports of infectious myocarditis, six reports of eosinophilic myocarditis, four reports of autoimmune myocarditis, four reports of hypersensitivity myocarditis, four reports of septic myocarditis, two reports of immune-mediated myocarditis, two reports of mycotic myocarditis, two reports of post-infection myocarditis, one report of giant cell myocarditis, and one report of bacterial myocarditis.
There are 9,186 reports of pericarditis, 72 reports of pleuropericarditis, 45 reports of viral pericarditis, 16 cases of infective pericarditis, 14 reports of constrictive pericarditis, two cases of bacterial pericarditis, one report of cytomegalovirus pericarditis, one report of adhesive pericarditis, one report of lupus pericarditis, one report of rheumatic pericarditis, one report of tuberculous pericarditis, one report of uraemic pericarditis, and one report of purulent pericarditis.
There are 1,461 reports of Guillain-Barré syndrome, 3,195 cases of Bell’s palsy, 4,162 reports of a cerebrovascular accident, and 1,443 cases of a cardiac arrest.
Also listed are 22,145 reports of menstrual disorders, 31,455 reports of vaccination failure, 22,873 reports of tachycardia, and 17,259 cases of herpes zoster.
The cut-off date for statistics about adverse events that are provided in the DAEN is two weeks behind the search date (a search on September 25, 2022, provides data up to September 11).
Reports of adverse reactions after the administration of Comirnaty, Vaxzevria, Spikevax, and Nuvaxovid, plus cases in which the vaccine brand was not specified.
The following data is up to September 11.
Reports about COMIRNATY
- Number of reports (cases): 79,827
- Number of cases with a single suspected medicine: 77,666
- Number of cases where death was a reported outcome: 408
DAEN reports about children dying after the administration of COMINARTY
In this first case, the seven-year-old boy died, but discovering this via the DAEN is not straightforward. The fact that this was a fatality is indicated in a separate listing.
In this second case, the nine-year-old girl died. Again, discovering this via the DAEN is not straightforward. The fact that this was a fatality is again indicated in a separate listing.
In this third case (report dated May 6, 2022), no specific details are given about the ten-year-old boy’s death, which is simply described as an ‘adverse event following immunisation’.
In this fourth case (report dated May 10, 2022), the five-year-old boy is reported to have suffered a cardiac arrest and abdominal pain.
A fifth case – that of a six-year-old boy about whose death no details were given – is no longer listed. This fatality had previously been referred to as an ‘adverse event following immunisation’. Below is the earlier DAEN entry:
Other DAEN reports about five- to 11-year-olds
There was previously an entry in the DAEN (pictured below) that provided details about a death after the administration of Comirnaty that involved hydrops foetalis, a condition in a foetus that is characterised by an accumulation of fluid, or oedema, in at least two foetal compartments (case number 746201).
There is still an entry on the DAEN for case number 746201, but it has been altered. The new entry refers to a foetal death, but gives none of the detail provided in the earlier listing and the case is not coded as a death or included in the total of deaths for that date.
On the DAEN, as of July 29, there were 12 reports of foetal death after Covid vaccination during pregnancy, but only one is actually coded as a fatality.
There are also 15 cases of foetal hypokinesia (abnormally decreased foetal movement) listed.
In many cases, the DAEN reports cite multiple symptoms.
Reports about Vaxzevria
- Number of reports (cases): 47,899
- Number of cases with a single suspected medicine: 46,804
- Number of cases where death was a reported outcome: 470
Again, in many cases, the reports cite multiple symptoms.
REPORTS about SPIKEVAX
The Moderna vaccine was first administered to Australians on September 22, 2021, and was provisionally approved as a booster dose on December 8, 2021.
The TGA said that, as of September 18, about 5.4 million doses of the vaccine had been administered in Australia.
- Number of reports (cases): 7,167
- Number of cases with a single suspected medicine: 6,882
- Number of cases where death was a reported outcome: 31
The death of a 14-year-old girl from New South Wales on October 20, 2021, after administration of the Moderna vaccine has been the subject of a Freedom of Information request to the TGA. The case is still under review.
REPORTS about Nuvaxovid
- Number of reports (cases): 895
- Number of cases with a single suspected medicine: 845
- Number of cases where death was a reported outcome: 3
One case reported after the administration of Nuvaxovid lists 42 suspected adverse reactions (this case is dated April 5). The age of the patient is not given.
There is a a listing on the DAEN dated May 25 about a person who died after receiving Nuvaxovid.
The other of the two reported deaths is coded as an ‘adverse event following immunisation’.
As of September 18, there were 666 reports on the DAEN of adverse reactions after Covid vaccination, including 26 deaths, in which the type of Covid-19 vaccine is not specified. A total 597 of the reports relate to “a single suspected medicine”.
There were 294 reports on the DAEN of miscarriage after Covid vaccination (all vaccines).
The TGA reiterates that publication of an adverse event report does not necessarily mean that the event is related to the vaccine in question.
The administration states that “the protective benefits of vaccination against Covid-19 far outweigh the potential risks of vaccination”.
The TGA’s Covid-19 vaccine safety reports are now being published fortnightly instead of weekly.
The Sydney Local Health District admitted, and apologised for, the mistaken vaccination of a group of students at St Joseph’s College in Hunters Hill.
A smaller group of Aboriginal students were due to receive the Pfizer-BioNTech vaccine, but “through an error, the wider group of boarders in Year 12, a total of 163 students, were also vaccinated”, the chief executive of the health district, Teresa Anderson, said on July 6, 2021.
“All Aboriginal people aged 16 to 49 years of age are eligible for Covid-19 vaccination, according to the Commonwealth government eligibility criteria as they have a higher risk of acquiring, and developing severe disease from, Covid-19,” Anderson said.
“It was agreed that the Aboriginal students would be vaccinated through the state health system at Royal Prince Alfred Hospital’s vaccination hub.”
There was shock at the response of the New South Wales health minister, Brad Hazzard, when a reporter asked him about the error.
Hazzard snapped at the journalist and said: “You know what; the school intended it well. There was a mistake and so what? It’s happened. Out of a million vaccinations. Move on!”
A petition was launched on change.org calling on the prime minister, Scott Morrison, to sack Hazzard immediately “and apologise in writing to all students at St Joseph’s College who wrongfully received the Pfizer Covid vaccine”.
Reports from France
UPDATE: The ANSM has published data that covers the period up to April 7, 2022, the period up to May 5, the period up to May 23, the period up to June 16, the period up to July 21, and the period up to September 8. A report on the latest data will be available on here soon.
The agency also published a brief report on June 23 about menstrual disorders after Covid vaccination. As of April 28, 2022, researchers at the regional pharmacovigilance centres in France had analysed 9,381 reports of menstrual disorders after the administration of Comirnaty and 1,557 such reports after the administration of Spikevax. As of the same date, 58 million people in France had been vaccinated with Comirnaty and 12 million people had received a Spikevax vaccination.
Apologies to Changing Times readers for the delay in providing up-to-date statistics about adverse event reports in France.
France’s National Agency for the Safety of Medicine and Health Products (the ANSM) said in the status report it published on February 18, 2022, which covers the period up to February 10, that, since Covid vaccination began in the country on December 26, 2020, there had been 141,508 reports of adverse reactions, 25% of which it considers to be serious.
The agency doesn’t give clear, easily accessible information about the number of deaths in France reported after Covid vaccination, but a tally of figures given in individual summaries indicates that there have been at least 1,762.
ANSM reports indicate that there have been at least 1,364 deaths after administration of Comirnaty, 243 following administration of Vaxzevria, 116 after administration of Spikevax vaccine, and 39 after administration of the Janssen Biotech vaccine.
The Janssen vaccine was first used in France on April 24, 2021 (for people aged 55 years and above).
According to Worldometers.info, 138,135 people were reported to have died from Covid-19 in France as of February 28, 2022.
In its report published on February 18, the ANSM said that more than 139,197,900 vaccine doses had been administered as of February 10. Of these, more than 107,167,500 were doses of Comirnaty, more than 23,075,900 were Spikevax doses, more than 7,853,900 were doses of Vaxzevria, and more than 1,082,400 were Janssen Biotech doses.
A total 4,115 new adverse reaction reports were registered from January 28–February 10, the ANSM said, and 30% of these cases were considered to be serious. More than 3,012,500 vaccine doses had been administered during that period, the agency added.
The ANSM said 89,758 adverse reactions had been reported after vaccination with Comirnaty as of February 10 and 26% were considered serious. A total 2,933 of the cases were reported from January 28–February 10, and 30% of these were considered serious.
The agency said that, as of February 10, it had received 28,764 adverse reaction reports relating to administration of Vaxzevria, of which 23% were considered serious. Most of the symptoms were flu-like, but were often intense (e.g. high fever, muscle pain, and headaches), the ANSM said. A total 91 of the cases were reported from January 28–February 10 and 44% of these were considered serious.
As of February 10, 21,611 adverse reactions had been reported after administration of the Moderna (Spikevax) vaccine, 19% of which were considered serious, the ANSM said. A total 1,061 cases were reported from January 28–February 10 and 28% of these were considered serious.
In its most recent status report the ANSM said it had received 1,375 reports of adverse reactions after administration of the Janssen Biotech vaccine, 38% of which were considered serious. A total 30 of the cases were reported from January 28–February 10 and 47% of these were considered serious.
The agency said in an earlier status report that it had received 267 reports of adverse reactions after the administration of a series of at least two different vaccines. These included 107 reports of serious cases.
The ANSM said in its latest status report that the suspected adverse reactions to Comirnaty for which there was a potential safety signal or which were already being specifically monitored included cardiac rhythm disorders; nervous system, gastrointestinal, vascular, and respiratory disorders; venous cerebral thrombosis; thrombocytopenia; spontaneous hematomas, an imbalance in sugar levels, and paediatric inflammatory multisystem syndrome (PIMS); vaccine failure; acute pancreatitis; varicella zoster meningoencephalitis, idiopathic aplastic anaemia, and rheumatoid polyarthritis; acquired haemophilia; glomerulonephritis; menstrual disorders; Parsonage Turner syndrome; ear disorders; and a reactivation of the Epstein-Barr virus.
The agency said there were also confirmed safety signals for arterial hypertension, myocarditis, and pericarditis.
The ANSM said earlier that, as of November 11, 2021, it had received 65 reports of cerebral venous thrombosis after the administration of Comirnaty. In 27 cases, the thrombosis occurred after the first vaccination and, in 32 cases, it occurred after administration of the second dose. In six cases, this information was not available.
In 39 of the cases, the patients were female, the ANSM said, and, in nearly half of the cases the thrombosis occurred more than 15 days after vaccination.
The agency said no link between the thrombosis and the vaccine had been established.
The ANSM said its monitoring committee had identified reports of autoimmune hepatitis and polymyalgia rheumatica (also known as Forestier-Certonciny syndrome) following administration of Comirnaty as potential safety signals and had communicated this to the EMA. No link had as yet been established with the vaccine, the ANSM said.
Fourteen cases of autoimmune hepatitis were reported as of November 11, 2021, the ANSM said. In two of the cases, the diagnosis of autoimmune hepatitis was not established and, in five cases, the information provided was insufficient to evaluate the role of the vaccine.
“The seven other cases analysed occurred in five women and two men aged between their forties and nineties in an average time period of 21 days after vaccination,” the agency added. “Three cases occurred after the first dose, three occurred after the second dose, and, in one case, this information wasn’t provided.”
Seventy cases of polymyalgia rheumatica had been identified after administration of the Pfizer-BioNTech as of November 11, 2021, the ANSM said. The average age of the patients was 72 years, the agency added, and 51,5% of them were women. Thirty-two of the cases occurred an average of 11 days after the first vaccination and 38 occurred an average of 25 days after the second dose. The condition of the patients improved rapidly after treatment with cortisone, the ANSM said.
In its previous status report, the agency said there had been 27 reports of polymyalgia rheumatica after the administration of Vaxzevria and this was considered to be a potential safety signal. In 23 cases (in 14 men and nine women with a median age of 70 years) it was considered to be very probable that the patient did have polymyalgia rheumatica.
In 13 cases, symptom onset was after the first injection. Onset was after the second dose in ten cases. The median onset interval was eight days. Again, the condition of the patients improved rapidly after treatment with cortisone, the ANSM said.
REPORTS ABOUT THE SPIKEVAX VACCINE
The ANSM said in its most recent status report that it had received five reports of cases of acquired haemophilia after the administration of Spikevax (three of the reports concerned men and, in two cases, the patient was female). The patients’ median age was 76 and symptom onset was between two and 67 days after vaccination.
“At this point a link with the vaccine cannot be established, but, given the rarity of this event, and the documented cases, these events will, as of now, be closely monitored,” the ANSM said.
The ANSM also said it had received reports of eight cases of autoimmune hemolytic anaemia, a condition in which the immune system destroys red blood cells (four of the reports concerned men and, in four cases, the patient was female). The patients’ median age was 71 and symptom onset was between three and 59 days after vaccination. One case occurred after a booster dose. Seven of the patients were hospitalised.
The ANSM again said a link with the vaccine could not be established, but, given the rarity of the event, and the documented cases, the events would, as of now, be closely monitored.
The agency said that, in the case of the Moderna vaccine, the list of suspected adverse reactions for which there was a potential safety signal or which were already being specifically monitored included transitory amnesia, hearing disorders, loss of consciousness, thyroiditis, musculoskeletal problems, rheumatoid polyarthritis, glomerulonephritis, menstrual disorders, Parsonage Turner syndrome, tinnitus, and antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis.
There were confirmed safety signals for arterial hypertension, myocarditis and pericarditis, and erythema multiforme, the ANSM said.
Reports of autoimmune hepatitis following administration of the Moderna vaccine have also been identified as a as potential safety signal and this has been communicated to the EMA. The ANSM said no link had as yet been established with the vaccine.
The agency specified earlier that four cases of autoimmune hepatitis had been reported as of November 11. Three of the patients were female and symptom onset was an average of 45 days after vaccination. Three of the cases occurred after administration of the second vaccine dose.
The ANSM also said earlier that it had recently seen an increase in reports of persistent musculoskeletal problems after primary Covid vaccination.
The agency said that, as of January 6, it had not identified a safety signal relating to musculoskeletal problems after Covid vaccination, but the problems had been seen to persist for more than three weeks after initial joint pain.
Since December 3, 2021, 69 cases of musculoskeletal problems had been reported after Covid vaccination, the ANSM said. Fifteen of the cases were considered to be serious and the average age of those affected was 51.4 years. Average symptom onset was 8.8 days. Forty-three of those affected were female and 26 were male.
The ANSM also said it had received reports of two cases of ANCA-associated vasculitis after administration of the Moderna vaccine (in one case after the first dose and, in the other case, after the second dose).
One patient was in their sixties and one was in their eighties. In one case initial symptoms appeared one day after vaccination and, in the other case, they appeared six weeks after vaccination.
Nine cases of cerebral venous thrombosis had been reported after administration of the Moderna vaccine, the ANSM said. The average age of those affected was 44.7 days and symptom onset was an average of 19.2 days. Five of those affected were hospitalised and one patient died, the ANSM said.
The ANSM said that no link with the vaccine had been established, but there was specific monitoring of the incidence of cerebral venous thrombosis after administration of the Moderna vaccine.
The ANSM said in an earlier ‘Focus’ report about the Moderna vaccine that it had received 19 reports of cases of pancreatitis post vaccination. The average symptom onset interval was 22.6 days and the patients’ median age was 54. In more than 63% of cases the patients had antecedents that could explain the onset of pancreatitis, the ANSM said.
Fifteen of the patients were hospitalised and one of them died.
The ANSM said in a previous status report that it had received 15 reports of cases of thyroiditis after administration of the Moderna vaccine, eight of which it considered to be serious. The average age of those affected was 44.4 years, the agency said, and average symptom onset was 13.4 days after vaccination. Nine of the patients were female and six male.
“In the case of neck pain, swelling of the neck, intense fatigue, or post-vaccination palpitations, healthcare professionals are advised to investigate whether the cause is thyroiditis,” the agency said.
The ANSM said in a special ‘Focus’ report that it had received 29 reports of thyroid disorders after administration of the Moderna vaccine, 11 of which it considered to be serious.
The agency added that it had received 54 reports of thyroid disorders after the administration of Comirnaty. Forty-nine of those affected were women. The median onset interval was 83 days after vaccination but the interval varied depending on the disorder that occurred, e.g. it was 22 days for cases of hyperthyroidism, 20 days in cases of hypothyroidism, 70 days in the case of Basedow’s disease (Graves’ disease) and 14 days in the case of Hashimoto’s thyroiditis.
In eight cases, the person affected had antecedent thyroid problems.
The ANSM said earlier that, as of November 11, it had received 123 reports of cases of tinnitus, 27 of which it considered to be serious. Eighty of those affected were female, the agency added. Median symptom onset was three days and the patients’ median age was 46 years.
Seventy-five cases occurred after the first vaccine dose and 37 occurred after the second dose (this information was not available in one case).
The ANSM said there would be specific monitoring of cases of tinnitus, but, at this stage, the agency said, no link with the vaccine had been established.
In its summary published on December 3 the ANSM said it had received a report of one recent case of Lyell’s syndrome (toxic epidermal necrolysis) after the administration of the Moderna vaccine.
Lyell’s syndrome is a rare, potentially life-threatening mucocutaneous disease.
In a special report about Moderna the ANSM specified that the patient was 16 years old and symptom onset was three days after the second vaccine dose.
Three other cases of Lyell’s syndrome had already been reported after administration of Comirnaty.
The ANSM said that analyses at regional centres of pharmacovigilance did not currently indicate that the mRNA vaccines may have caused the syndrome.
The agency also said in a previous report that it had received six reports of suspected Creutzfeldt-Jakob disease after Covid vaccination. Four of the cases were after administration of Comirnaty, one was after administration of the Moderna vaccine, and one was after administration of Vaxzevria.
The ANSM said that, after an in-depth analysis, its monitoring committee said that, given the rapid onset of symptoms in the six cases, it could not conclude that Covid vaccination played a role in the onset of the disease.
12- to 18-year-olds
In its most recent status report the ANSM said that, as of February 3, 2022, it had received 2,650 reports of serious adverse reactions in 12- to 18-year-olds after the administration of Comirnaty, 718 of which were considered to be serious.
Vaccination of 12- to 18-year-olds with Comirnaty began in France on June 15, 2021. More than 9.7 million doses of the vaccine had been administered to 12- to 18-year-olds as of February 3, the ANSM said.
The ANSM said earlier that nine cases of PIMS had been reported in 12- to 16-year-olds (eight male and one female) after the administration of Comirnaty. Symptom onset ranged from four to 42 days. Five of the cases occurred after the first dose and four after the second dose. All of the patients recovered, the ANSM said.
On July 28, France’s National Health Authority (HAS) recommended administration of the Moderna vaccine to 12- to 18-year-olds.
On November 8, however, the HAS recommended that, when it was available, Comirnaty should be administered to people aged under 30 years, whether for the primary vaccination series or a booster.
The agency said earlier that it had received two reports of facial paralysis in 12- to 18-year-olds after administration of the Moderna vaccine and twenty reports of menstrual disorders, five of which occurred after the second vaccine dose.
The cases of suspected adverse reaction reported between November 5 and December 2, 2021, included one case of proximal motor dysfunction in a 15-year-old that hampered the patient’s ability to walk and a case of behavioural disorder and psychomotor retardation in another 15-year-old who had a history of autism. The patient’s disorders persisted two months after the first vaccine dose.
There was also a report of a case of immune thrombocytopenia in a 16-year-old forty days after the second vaccine dose.
The ANSM also reported earlier that, in one case, an adolescent survived a heart attack but died after the onset of disseminated intravascular coagulation. The adverse reactions started 11 days after the first vaccine dose.
In a special “Focus’ report about Comirnaty, covering data up to December 2, the ANSM said that, of 558 reports of serious adverse reactions among 12- to 18-year-olds after administration of the vaccine, 270 concerned 12- to 15-year-olds.
The reports included 87 reports of myocarditis and 43 cases of pericarditis, 21 cases of facial paralysis, and 20 reports of convulsions.
There were also 18 reports of chest pain, 14 cases of gynaecological problems, 12 cases of immune thrombocytopenia (formerly known as idiopathic thrombocytopenic purpura), seven reports of liver disorders, six cases of PIMS, five cases of pancreatitis, four reports of a pulmonary embolism, three reports of Guillain-Barré syndrome, one case of retinal artery occlusion, and a case of minimal pleural effusion.
The administration of Comirnaty has been authorised for five- to 11-year-olds in France since December 20, 2021.
As of February 3, 2022, more than 350,000 doses had been administered to the age group in France, the ANSM said, and the agency had received reports of 48 cases of adverse reactions, including four that were considered to be serious.
In its ‘Focus’ report about Comirnaty that includes data up to February 3, the ANSM said that, in 29 of the 48 cases, the adverse reaction was the result of a medical error. Twenty cases were “without effect”, the ANSM said.
In its latest ‘Focus’ report, the ANSM only gives details about the three most recent cases. Two were reported to be “without effect” and related to dosage (in one case the child was given an adult dose of 30 micrograms and, in another, the dose given to an 11-year-old girl was not diluted before being injected). In the one case reported to have resulted in an adverse effect the child was also given an adult dose.
In an earlier report the ANSM said that, in 26 of the 29 cases reported as of January 6, the adverse reaction was the result of a medical error. In 18 cases that the ANSM says were “without effect”, the vaccine was administered (between July and August 2021) to 11-year-olds in four different regions when children of that age were not scheduled to receive Covid vaccination.
In eight cases the medical error did have an effect, the ANSM said. In six cases, the reports were of local or systemic reactogenicity. One was a case of an asthma attack and one was a case of malaise. Four of those affected were 11-year-olds who were vaccinated in July/August 2021 and in the other four cases, there was an error in preparation of the vaccine (an adult dose of 30 micrograms rather than the 20-microgram dose authorised for children).
The other three of the 29 cases were reactions such as fever, nausea, and vomiting, the ANSM said.
The 29 adverse reactions occurred in 20 boys and nine girls. Their average age was 10.5 years.
The ANSM says no safety signal has been identified for five- to 11-year-olds.
Adverse reactions reported after booster doses
The administration of booster Covid vaccinations to people aged 65 years and above, and those at risk of severe Covid, started in France on September 1, 2021.
From October 6, the administration of boosters was extended all professionals working with vulnerable people and individuals in the entourage of people who are immunosuppressed.
On November 8, the HAS recommended that a 50-microgram dose of the Moderna vaccine should be used as a booster for people aged 30 years or more who had received a different Covid vaccine in their primary vaccination series.
From November 27, booster Covid vaccination was extended to all adults in France (the Pfizer-BioNTech or Moderna vaccine for people aged 30 years and above but only Comirnaty for people aged under 30 years).
The ANSM said that, as of February 3, 2022, about 25.9 million booster doses of Comirnaty had been administered.
In a special ‘Focus report’ about Comirnaty, covering data up to February 3, the ANSM said it had received reports of 1,337 cases of serious adverse reactions after booster doses of the vaccine (in 807 cases those affected were female and, in 570 cases, they were male). The largest number of cases (276) occurred in the 70- to 79-years age group.
In 540 cases the person was hospitalised and, in 117 cases, the patient died. Nineteen of the patients died after being infected by SARS-CoV-2, seven suffered an ischemic stroke, and six had a cardiac arrest.
Twenty-two patients became invalids or were incapacitated.
Of the 1,337 cases, 105 were reports of a pulmonary embolism. There were 96 cases of pericarditis, 40 cases of myocarditis, 73 cases of an ischemic stroke, 43 cases of deep vein thrombosis, 39 reports of arterial hypertension, 23 reports of convulsions, 16 reports of immune thrombocytopenia, and 13 reports of of Guillain-Barré syndrome. In 74 cases the person tested positive for SARS-CoV-2.
The ANSM said it had received 30 reports of cases of hypersensitivity or an anaphylactic reaction after a Comirnaty booster.
In an earlier report the agency said that, in one case, a person in their fifties who had an anaphylactic reaction 15 minutes after the injection suffered paresthesia in their arms and legs then, after a further 15 minutes, had hypotension, dyspnea (shortness of breath), and angioedema (giant hives).
The ANSM said in a special ‘Focus’ report covering data up to February 3, 2022, that it had received 1,381 reports of adverse reactions after the administration of booster doses of the Moderna vaccine, 361 of which it considered to be serious. In 123 cases the person was hospitalised and, in 14 cases, the patient died.
All of the patients who died had cardiovascular risk factors and serious comorbities, the ANSM said.
The agency added that, from February 4–11 it received an additional 261 reports and in 70 cases the adverse events were considered to be serious.
As of February 3, more than 11.4 million Moderna booster doses had been administered in France, the ANSM said.
In an earlier ‘Focus’ report about Moderna, which covered data up to January 6, the ANSM said that, in one of the cases of death after a booster dose, the person suffered a cardiac arrest 15 minutes after the booster was administered.
The ANSM said previously that, from November 5 to December 13, it had received 62 reports of suspected adverse reactions after Moderna booster doses.
Three of the cases were thromboembolic events (one case of a pulmonary embolism 12 days after vaccination, one fatal case of cerebral thrombosis, and one case of retinal ischemia, which began on the day the booster dose was administered).
Two of the cases involved a loss of consciousness (with spontaneous recovery) the day after the booster was administered and one serious case of erythema nodosum (inflammation of the fat cells under the skin) that occurred 25 days after the booster.
Two of the cases were thromboembolic events (one case of deep vein thrombosis that occurred eight days after the booster vaccination, one case of a pulmonary embolism seven days after administration of the booster, and one case of Guillain-Barré syndrome two days after the booster and a flu vaccine were administered (the patient had a viral respiratory infection that started at least 15 days earlier).
A case of acute coronary syndrome was also reported in a person aged over 80 years who had several cardiovascular risk factors. It occurred seven days after the booster was administered.
One case of immune thrombocytopenia occurred 26 days after the booster and there was one fatal case of cardiorespiratory arrest in a patient aged over 75 years who had chest pains that began two days after the booster. This patient also had several cardiovascular risk factors.
The ANSM previously noted that, following a recommendation from the HAS on August 23, the national authorities recommended a booster dose of an mRNA vaccine to those who had received the single-dose Janssen vaccine, to be administered from four weeks after the initial vaccination.
In an earlier report about the Moderna vaccine, the ANSM said that one of the people who died after receiving a third dose of the Moderna vaccine was a 71-year-old who had received a kidney transplant and whose condition deteriorated two days after the third vaccine dose.
In one of its ‘Focus’ reports about the Moderna vaccine the ANSM said another of the people who died was a 66-year-old who was undergoing dialysis, was on a kidney transplant list, and had serious antecedent cardiac problems. The patient died the night after receiving a Moderna booster dose.
Reports about the Janssen vaccine
The ANSM said that, in the case of the Janssen vaccine, the list of suspected adverse reactions for which there was a potential safety signal or which were already being specifically monitored included myocarditis and pericarditis, vaccine failure, Parsonage Turner syndrome, arterial hypertension, heart attacks, and purpura rheumatica, also known as Henoch-Schonlein purpura, which is a disorder causing inflammation and bleeding in the small blood vessels.
The ANSM said it had received four reports of thromboses with thrombocytopenia after administration of the Janssen vaccine. Three of the patients were in their fifties and one was in their forties. Two of the patients were aged under 55 years.
The agency said earlier that it had received 13 reports of Guillain-Barré syndrome after administration of the Janssen vaccine; 51 reports of venous thromboembolic events, 47 of which it considered to be serious; 28 cases of visual impairment, including 14 that the ANSM considered to be serious; 26 cases of cardiac arrhythmia, including six that were considered to be serious; 21 cases of haemorrhagic disease, five of which the ANSM considered to be serious; and 21 cases of a cerebrovascular accident.
There were also reports of 11 cases of facial paralysis, nine of which the ANSM considered to be serious; ten cases of arthritis, including four cases of rheumatoid polyarthritis and two cases of polymyalgia rheumatica; seven cases of hearing disorders; six cases of thrombocytopenia; five cases of limb ischaemia (a sudden lack of blood flow to a limb); and two cases of an ischemic stroke.
There were also 16 reports of coronary illness. In 12 cases, the patients were male and the median age was 58.5 years. In 12 cases, the patient had cardiovascular risk factors.
The ANSM also said it had received 47 reports of arterial hypertension, 24 of which were considered to be serious, after administration of the Janssen vaccine. The agency said its monitoring committee considered that there was a potential safety signal and stepped-up monitoring would continue.
Additionally, there were four reports of myocarditis and two reports of pericarditis.
The ANSM had said previously that it had received two reports of immune thrombocytopenia after administration of the vaccine. In one of the cases it was unlikely that the vaccine was the cause as the patient had a history of the condition and a viral nasopharyngeal infection the previous week, the ANSM said. The second case was being investigated, the agency added.
In a special report about the Janssen vaccine, covering data up to December 30, 2021, the ANSM said it had received 118 reports of vaccine failure. Eight of the reports were excluded from the analysis. In four of these cases, the positive SARS-CoV-2 test occurred less than 21 days after vaccination, in two cases the vaccination date was previous to the Janssen vaccine’s authorisation in Europe, and two of the reports related to cases of long Covid being aggravated by vaccination.
The ANSM said 100 of the 110 cases analysed were considered to be serious and 61 of the patients were hospitalised. Seventeen of the patients died.
In nine of the 100 serious cases, the patients had suppressed immunity. In 21 cases, the person had no risk factor for severe Covid-19. Sixty-six of the patients were male and 34 female, the ANSM reported.
In one of the serious cases, the person had received two doses of the Janssen vaccine three months apart, contrary to the recommendation, which is for one dose only. Two months after the second dose the person was diagnosed with a Covid-19 pneumonia resulting from infection with the Delta variant and required treatment in an intensive care unit.
The median time gap between vaccination and vaccine failure was 64 days, the ANSM said.
The virus variant was known in 40 cases and, in 39 of those cases, the patients were infected by Delta. In one case the variant was Alpha.
The ANSM also said it had received one report of a case of transverse myelitis (inflammation of the spinal cord) in a patient in their fifties 38 days after administration of the Janssen vaccine. There was sudden neuropathic pain in the lumbar region followed rapidly by serious impairment of movement in the legs.
The patient was recovering, the agency added.
“This is a safety signal that is being investigated at a European level and is a potential safety signal in France and will be monitored,” the ANSM said.
The agency said it had also received reports after administration of the Janssen vaccine of two cases of Henoch-Schönlein purpura. The patients were women in their fifties and onset was between six days and one month after vaccination. Both patients were recovering, the ANSM said.
Reports about Vaxzevria
The ANSM said that, in the case of Vaxzevria, the list of suspected adverse reactions for which there was a potential safety signal or which were already being specifically monitored included increased arterial pressure, demyelinating disease of the central nervous system (CNS), the inflammatory condition erythema nodosum, ischemic colitis, hearing disorders, vaccine failure, myocarditis, pericarditis, pancreatitis, giant cell arteritis, and Parsonage Turner syndrome.
The agency said there was a confirmed safety signal about thrombosis with thrombocytopenia and the ANSM had received reports of 30 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT).
The agency said in its most recent special report about Vaxzevria, covering data from September 24 to December 30, 2021, that it had received reports of 30 cases of VITT after the administration of the vaccine.
The ANSM also said it had received 68 reports of cases of “atypical thrombosis” after administration of the vaccine and 471 reports of a pulmonary embolism.
The agency said it had received 491 reports of cases of peripheral thrombosis and 49 reports of hearing loss after administration of the vaccine. It added that its monitoring committee had concluded that the cases of hearing loss constituted a potential safety signal.
The ANSM said it had also received 292 reports of cases of an ischemic stroke, 652 reports of arterial hypertension, 755 reports of mucocutaneous bleeding, 475 reports of a reactivation of viral infection, including herpes zoster, 47 reports of Guillain-Barré syndrome, 80 reports of facial paralysis, and 15 cases of pancreatitis after administration of Vaxzevria.
The agency also received reports of 64 pericarditis and 19 reports of myocarditis after the administration of Vaxzevria.
The ANSM said that, since the start of vaccination with Vaxzevria in France, it had received 262 reports of vaccine failure that met the agency’s specific definition. In 181 cases the person affected was male and the median age was 69 years.
Of the 262 cases, 228 were considered to be serious.
The SARS-CoV-2 variant was identified as Delta in 80 cases and Alpha in two cases (this information was not available in 180 cases).
The ANSM says the person’s medical history was known in 234 cases. In 122 cases the person was overweight (there was obesity in 80 cases), 83 of the people were diabetic, 47 had respiratory illnesses, 16 were asthmatic, 41 had malignant tumours, 43 had cardiac problems, 21 had chronic renal insufficiency, and 16 had autoimmune diseases. One patient had had a kidney transplant. Only five patients had no risk factor.
A total 228 patients were hospitalised, including 78 who needed intensive care. Twenty-seven of the patients died.
In its previous general summary, the ANSM said it had received 476 reports of a reactivation of viral infection, 100 of which it considered to be serious. The median onset interval was seven days.
In most cases, there was a reactivation of a herpes virus (in 383 cases the varicella-zoster virus). In two cases, there was reactivation of the hepatitis E virus and, in one case, hepatitis C was reactivated.
There was one fatal case of fulminant hepatic necrosis. The patient was infected by herpes simplex virus type 1 (HSV-1).
“The potential safety signal for shingles and herpes reactivation has been expanded to include cases of a reactivation of viral hepatitis and the Epstein-Barr virus,” the ANSM said.
The ANSM said in a previous summary that its monitoring committee had identified reports of sarcoidosis (a disease characterised by the growth of small collections of inflammatory cells in the body) and Still’s disease (a rare type of inflammatory arthritis that features fevers, rash and joint pain) as being potential safety signals for Vaxzevria and had communicated this to the EMA. The ANSM said that, at this stage, it did not consider that there was a link with the vaccine, but it would be attentively monitoring the reports.
Three cases of sarcoidosis had been reported after the administration of Vaxzevria, the ANSM said. The patients were two women and one man aged between 4 and 56 years and symptom onset was between 12 and 76 days after vaccination. In two cases, the symptoms occurred after the first vaccine does and in one case, they occurred after the second dose. In one case, the patient received Vaxzevria as a first dose and the Moderna vaccine as the second.
One case of Still’s disease had been reported, the ANSM said. The patient was a man in his fifties and symptom onset as 16 days after the first vaccine dose.
In France, since March 19, Vaxzevria has only been administered to people aged 55 years and above.
Mixing and matching Covid vaccines
In a special ‘Focus’ report on mixing and matching Covid vaccines (covering data up to January 20, 2022) the ANSM said it had received 892 reports of adverse reactions, 841 of which met its stated definition. The ANSM considered 318 of the 841 cases to be serious.
The reports related to 551 women and 290 men with a median age of 54 years.
A total 110 of the patients were hospitalised and 19 died.
The ANSM said that over the period covered by the latest ‘Focus’ report (December 24, 2021, and January 20, 2022), 80% of the cases reported related to a three-dose schedule and in most of these cases (229) there was an mRNA/mRNA mix (Comirnaty/Comirnaty/Spikevax in 160 cases).
Of the 11 deaths that occurred between December 24, 2021, and January 20, 2022, six were after administration of an mRNA/mRNA vaccine mix and seven followed administration of an adenovirus-vectored/mRNA vaccine mix.
Seven of the patients who died were male and four were female and their median age was 71 years. In two of the cases, the patient was aged under 50 years. The deaths occurred a median of three days after the last vaccine dose.
There were cardiovascular antecedents in nine cases.
Among the 841 reported cases of adverse reactions, there were 12 cases of vaccine failure, of which ten were considered to be serious (six of these patients were hospitalised). Seven of the patients were aged over 66 years and had risk factors for serious Covid-19.
In an earlier report, the ANSM said there had been more reports of serious adverse reactions among those who received the AstraZeneca-Oxford/Moderna mix than among those who received the AstraZeneca-Oxford/Pfizer-BioNTech mix.
Myocarditis and pericarditis
Cases of myocarditis reported in France have been the subject of investigation at European and national level. The results of a pharmaco-epidemiological study by the French group of scientific experts EPI-PHARE were published on November 8, 2021.
After the EPI-PHARE study confirmed that there was a risk of cardiac inflammation associated with mRNA vaccines, the French National Health Authority advised against use of the Moderna Covid vaccine for people aged under thirty.
The results of the study showed that, for people aged between 12 and 50 years, there was an increased risk of hospitalisation for myocarditis and pericarditis in the seven days after administration of the Pfizer-BioNTech and Moderna vaccines.
The risk was highest among young men aged under 30 years, the researchers found.
EPI-PHARE said the risk was higher with the Moderna vaccine than with Comirnaty, particularly after the second dose.
While the incidence of myocarditis and pericarditis among women was lower than among men, the risk increased among women aged under 30 years after the second dose of both mRNA vaccines, the researchers found.
On November 10, Germany’s Standing Committee on Vaccination (STIKO) also said that only the Pfizer-BioNTech Covid vaccine should be given to people under the age of thirty.
The committee said it was basing its decision on new safety data from the Paul Ehrlich Institute and other international data and that the recommendation applied to both the basic vaccination schedule and any booster vaccinations.
Even if a different vaccine was previously used, further vaccinations should be carried out with Comirnaty, the STIKO said.
The STIKO said that, even though there were no comparative safety data for the Pfizer-BioNTech and Moderna vaccines in relation to the vaccination of pregnant women, it was also recommending that pregnant women, regardless of their age, should only be offered Comirnaty.)
The ANSM said in its previous status report that researchers at the regional pharmacovigilance centres had reviewed all the reports it had received of cases of venous and arterial thrombosis after administration of Vaxzevria and of venous thromboembolic events, and particularly myocardial infarction (heart attack), after administration of the Janssen vaccine.
This was after a study conducted by EPI-PHARE, which was published on January 18, 2022, demonstrated a slight increase in the risk of myocardial infarction and pulmonary embolism among 18- to 74-year-old adults in France in the two weeks after administration of a Covid vaccine that used an adenovirus vector (Vaxzevria and the Janssen vaccine).
On February 21, the HAS said it was recommending that the Janssen Covid vaccine should only be used in certain cases.
The HAS said that, in light of the new data contained in the report published by EPI-PHARE on January 18, and while the conclusions of the EMA were awaited, it was recommending that the vaccine only be given to people at risk of developing severe Covid-19 and for whom an mRNA vaccine was contraindicated.
The HAS said EPI-PHARE’s preliminary findings should be interpreted with caution and needed to be confirmed by international studies. The authority urged the EMA to study the data as rapidly as possible.
“At this stage, data that is available globally after the administration of 38 million doses of the Janssen vaccine are reassuring and there hasn’t been a safety signal about the heart attack risk, either at a European level or in the US,” the HAS said.
The ANSM said the analyses conducted at the regional pharmacovigilance centres indicated that the number of cases of pulmonary embolism (471) and of deep vein thrombosis without a pulmonary embolism (491) that were reported after vaccination with Vaxzevria was slightly higher in the two weeks after vaccination than the number of cases expected in the general population. This constituted a potential safety signal, the ANSM said.
“This finding accords with EPI-PHARE’s study and other international research,” the agency added. “The risk, if it exists, seems moderate and lower than that associated with Covid-19.”
Of the 471 cases of pulmonary embolism reported, 247 occurred within 15 days of vaccination, the ANSM said. A total 116 of the patients were female and 131 were male and the median age was 67. The total number of cases was slightly higher than the number expected in the general population, the ANSM said.
Of the 491 cases of deep vein thrombosis without a pulmonary embolism reported, 272 occurred within 15 days of vaccination, the agency said. A total 125 of the patients were female and 147 were male and the median age was 66.
“According to available data about the incidence of deep vein thrombosis without a pulmonary embolism, the number of cases could be very slightly higher than the number expected in the general population,” the ANSM said. This constituted a safety signal.
“This finding accords with EPI-PHARE’s study and other international research,” the agency added. “This venous thromboembolic risk, if it exists, seems moderate and lower than that associated with Covid-19.”
The agency added that 86 cases of myocardial infarction had been reported, including 61 that were reported with 15 days of vaccination with Vaxzevria. The median age of the patients (45 men and 16 women) was 63 years.
The agency said that, while the number of cases of myocardial infarction observed in the pharmacovigilance analysis wasn’t higher than the number expected in the general population, there was nevertheless a potential safety signal, given the EPI-PHARE researchers’ findings.
The ANSM said 16 cases of myocardial infarction had been reported after administration of the Janssen vaccine (12 of the patients were men and four were women and their average age was 58.5 years). Twelve of the patients had cardiovascular risk factors, the ANSM said.
The agency again said that while the number of cases of myocardial infarction observed wasn’t higher than the number expected in the general population, there was nevertheless a potential safety signal, given the EPI-PHARE researchers’ findings.
In an earlier EPI-PHARE study, whose results were published in July 2021, and which focused on people aged 75 years or more, researchers found that there was no evidence of an increased risk of myocardial infarction, an ischemic stroke, a haemorrhagic stroke, or a pulmonary embolism after either the first or second dose of the Pfizer-BioNTech vaccine.
The ANSM had said earlier that a preliminary analysis indicated that more cases of myocarditis were reported after administration of Comirnaty than would be expected in the general population aged under 50 years.
“The monitoring committee accepts the hypothesis that the Comirnaty [Pfizer-BioNTech] vaccine can have a role in cases of myocarditis and we are monitoring the myocarditis safety signal, particularly in the young population,” the agency said.
Myocarditis was a rare adverse reaction, the ANSM said, and the benefits of the vaccine still outweighed the risk.
The ANSM said in an earlier summary that, as of October 14, it had received reports of 106 cases of myocarditis, including reports of 62 cases in people aged under 30 years, after administration of the Moderna vaccine.
“These cases are mostly among males, after the second vaccine dose, and 87% of the patients are recovering,” the agency said. In 76% of the cases, the adverse reaction occurred within seven days of vaccination, the ANSM added.
“After the suspension in certain Nordic countries, for precautionary reasons, of use of the Moderna vaccine for those aged under 18 or 30 years, a new review of cases of myocarditis in the under-30s was carried out by the regional pharmacovigilance centres,” the agency said.
The ANSM said that data was still limited, but the rate of reporting of cases of myocarditis after two doses of the Moderna vaccine among males aged between 18 and 29 years appeared to be higher than that observed among males in the same age group who received two doses of Comirnaty.
In a special report about the Moderna vaccine, the ASM said that, as of December 2, it had received 15 reports of cases of myocarditis in 12- to 18-year-olds, 12 of which occurred after the second dose. The youngest patient was 15 years old.
Two cases of pericarditis were reported in 12- to 18-year-olds, one of which was after the second vaccine dose.
Parsonage Turner syndrome
The ANSM said in an earlier report that it had received reports of three cases of Parsonage Turner syndrome after administration of the Janssen vaccine. The patients (two male and one female) were aged between 51 and 71 years and symptom onset was between 10 and 22 days after vaccination.
The syndrome is a neurological disorder characterised by sudden, excruciating shoulder pain, followed by severe weakness caused by nerve damage.
The agency also said it had also received reports of eight cases of the syndrome after administration of Vaxzevria.
The ANSM also said in a previous summary that it had received reports of eight cases of Parsonage Turner syndrome after administration of Comirnaty.
The patients (four men and two women) were aged between 19 and 69 years and the adverse reaction occurred between one and fifty days after vaccination, the ANSM said. In half of the cases, the reaction occurred after the first dose and, in the remaining cases, it occurred after the second dose.
The ANSM said that four of the patients were reported to be recovering, but it did not have information about the other two.
The agency also said two cases of Parsonage Turner syndrome had been reported after administration of the Moderna vaccine. Both of the people affected were men and both were recovering, the ANSM said.
One of the men was in his thirties and one was in his sixties and the adverse reaction occurred between one and 17 days after vaccination, the ANSM added. One case occurred after the first vaccine dose and one after the second.
The ANSM said its monitoring committee considered that there was a potential safety signal for Parsonage Turner syndrome in the case of the two mRNA vaccines and the AstraZeneca-Oxford and Janssen vaccines.
The ANSM’s monitoring committee says there is a potential safety signal relating to reports of menstrual disorders after administration of the Moderna and Comirnaty vaccines.
The agency said in a previous report that it had received 3,870 reports of menstrual disorders after administration of Comirnaty, of which 89 were considered to be serious. The median age was 33 years and, in 57.4% of the cases, onset of the disorder was reported to be less than seven days.
In 47.7% of the cases, the disorder occurred after administration of the first vaccine dose and in 42.2% it occurred after administration of the second dose. In 178 cases, the menstrual problems occurred after the administration of both doses.
The ANSM also said it had received 562 reports of menstrual disorders after administration of the Moderna vaccine, 29 of which were considered to be serious. The women’s media age was 27 and symptom onset in the case of abnormal bleeding was a median of three days after vaccination. In more than 46% of the cases, the disorder occurred after administration of the first vaccine dose and in more than 47% of cases it occurred after administration of the second dose.
The agency reiterated in its most recent report that the effects were mainly of two types: abnormal bleeding (intermenstrual bleeding and heavy periods) and delayed menstruation and amenorrhea. There were reports of menstrual disorders after the first vaccine dose and after the second dose, the ANSM said.
The ANSM said that, in most cases, the menstrual disorders were of a short duration, and resolved spontaneously. “At present, it is not possible, on the basis of the available data, to establish a direct link between Covid vaccination and these menstrual disorders,” the agency added.
The agency said in an earlier summary that there were reports of women experiencing menstrual disorders following Covid vaccination after their menopause and this constituted a potential safety signal.
The ANSM also said in an earlier summary that, as of July 1, it had received 52 reports of liver disorders after administration of the Pfizer-BioNTech and Moderna vaccines. Thirty-five of the cases occurred after the first vaccine dose and 15 after the second dose. In two cases, this information was not available to the agency.
Two of the patients died (one was in their nineties and one was in their seventies), and 11 were reported at that time to still be unwell.
Two of the patients (one in their seventies and one in their eighties) developed autoimmune hepatitis and, in the case of three patients, including one of the people who died, there was a resurgence of earlier autoimmune hepatitis. The three patients were in their forties, seventies, and nineties.
The ANSM said it could not be concluded that the vaccine caused the reported cases of liver disorders, which were mainly in elderly people.
The agency also said that, in the case of the fatalities reported after administration of Comirnaty, the information it had to date did not indicate that the vaccine was potentially to blame.
The ANSM said it had also received 52 reports of liver disorders after administration of Vaxzevria. In three of the cases the patient had hepatic thrombosis and in three cases the patient had infectious hepatitis. Three patients had autoimmune hepatitis. In one of those cases there appeared to be a resurgence of the disease in a patient in their seventies. In one of the other cases, the patient died.
In the 43 other cases (27 women and 16 men) onset was in a median of 9.5 days and the median age was 62. Twenty-three of the cases were serious, the ANSM said. In 22 cases, the patients’ condition was improving, the agency added.
The ANSM has also received one report of a case of hepatitis after administration of the Janssen Biotech vaccine. The patient was a woman in her sixties.
In an earlier summary, the ANSM said that 22 severe cases of rheumatoid arthritis had been reported among patients with an average age of 56.2 years. Twenty-one of the patients were women. In 15 of the cases, the patients had a history of rheumatoid arthritis. In two of the cases, there was a “positive rechallenge” (a reappearance of symptoms).
The cases indicated a potential safety signal for mRNA vaccines (Pfizer-BioNTech and Moderna) and would be reported at the European level, the agency said.
The agency also said earlier that it had received 12 reports of glomerulonephritis (a group of diseases that injure the part of the kidney that filters blood). In eight of the cases, there was a resurgence of the disease and the patients were aged between 20 and 60 years. Six of these cases occurred after the first vaccine dose and two after the second dose, and the onset interval was between one and thirty days.
In the four other cases, the patients were aged between 50 and 70 years and symptom onset was after the first vaccine dose, between two and 21 days after vaccination.
The ANSM said these cases also indicated a potential safety signal for mRNA vaccines (Pfizer-BioNTech and Moderna).
The agency said it had also received three reports of severe cases of rheumatoid arthritis and three reports of glomerulonephritis after administration of the Moderna vaccine. These cases would also be reported at the European level, the ANSM said.
In a previous summary the ANSM reported on a case of anaphylactic shock that led to the death of a person in their twenties ten hours after vaccination with Comirnaty. The agency said that no adverse effect had been observed immediately after vaccination.
The ANSM said that, given that the person died ten hours after vaccination and was “very probably” exposed after vaccination to an allergen, and given that the person had a history of food allergies, it could not be concluded that the death was caused by the vaccine.
The agency said it had received 28 reports of severe anaphylactic reactions after administration of Comirnaty.
The ANSM has also reported on the death of a patient in their seventies who suffered anaphylactic shock ten minutes after receiving the Janssen Biotech vaccine. The patient, who had no history of allergies, died six days later after being taken into intensive care.
Reports of Adverse reactions during pregnancy and breastfeeding
In its most recent status report, the ANSM said that most of the reports of adverse reactions after Covid vaccination that were about women who were pregnant or breastfeeding related to miscarriages.
The agency said that current data did not indicate that the miscarriages were linked to Covid vaccination and that there were risk factors in several cases.
“Miscarriages occur relatively frequently in the general population (in 12 to 20% of pregnancies, according to studies),” the ANSM said.
“Three recent studies (Zauche et al., Kharbanda et al., and Magnus et al.) have not found a link between miscarriages and mRNA Covid vaccines. A link with the vaccines has not been established.”
The ANSM said in a previous status report that it had received 29 reports of uterine contractions during pregnancy, 24 cases after administration of Comirnaty and five cases after administration of the Moderna vaccine.
The agency said that, in 18 of the cases, the contractions occurred between 30 minutes and 72 hours after vaccination and there was symptom regression within 72 hours in 13 cases. This, the ANSM said, was compatible with a potential role of the vaccine.
In the cases reported after vaccination with Comirnaty, most occurred within three days after vaccination, the agency said. Twelve cases occurred after the first vaccine dose and 11 after the second dose (in one case, this information was not available).
In nine of the 24 cases, the patient needed to be hospitalised. In one case, the contractions started six days after vaccination and neonatal death occurred after a premature birth at 22 weeks.
“In 13 of the 24 cases the chronology was very compatible with the vaccine having a role, and no risk factor for uterine contractions was identified,” the ANSM said. In four cases, there was a known risk factor, the agency added.
“Data about this matter is somewhat limited,” the ANSM said. “However, data about the risk of premature birth that could be a complication resulting from these contractions is reassuring (Lipkind et al.)”
The five reports of uterine contractions after administration of the Moderna vaccine occurred within three days of vaccination, the ANSM said. Three cases occurred after the first vaccine dose and two occurred after the second dose. In three of the cases the chronology was very compatible with the vaccine having a role and no risk factor for uterine contractions was identified, the ANSM said.
In one case, an anomaly in the cardiac rhythm of the foetus, associated with the contractions, which occurred 24 hours after vaccination, led to the woman needing to have an emergency caesarean in the 31st week of pregnancy.
The agency produced a special ‘Focus’ report about uterine contractions, including data up to January 6, 2022, in which it concluded that there was a possible link between the onset of uterine contractions and mRNA Covid vaccinations.
The ANSM said, however, that the cases of uterine contractions did not bring into question the risk-benefit equation, which was largely in favour of Covid vaccination of pregnant women.
The number of cases of uterine contractions remained very low, the agency said, and among those cases in which a link with Covid vaccination seemed possible, the patient recovered well in one to three days.
The ANSM recently published its 8th monthly pharmacovigilance report about adverse reactions to Covid vaccination among pregnant and breastfeeding women, which provides data up to December 3. The agency said there had been 472 reports of adverse reactions relating to the period of pregnancy, 326 of which were considered to be serious. Twenty deaths in utero were reported.Most of the adverse reactions reported in relation to pregnancy occurred after administration of Comirnaty, which is the Covid vaccine most administered to pregnant women in France, the ANSM said.
Since April 3, pregnant women in France have, from the second trimester, had priority access to an mRNA vaccine (either Pfizer-BioNTech or Moderna).
On July 21, France’s advisory committee for vaccine strategy said that women who wished to receive a Covid vaccine in their first trimester should be able to do so.
A total 399 of the adverse event reports (617 individual-symptom effects) followed administration of Comirnaty, 58 followed administration of the Moderna vaccine, and 15 followed administration of the AstraZeneca vaccine.
A total 159 of the reported adverse reactions after administration of the Pfizer-BioNTech were miscarriages, 15 were foetal deaths in utero, and five were ectopic pregnancies.
On average, the miscarriages occurred 24 days after vaccination. In 85 cases it occurred after the first vaccine dose and, in 72 cases, it occurred after the second dose. In two cases this information was not available.
Eighty-one of the miscarriages occurred within two weeks after vaccination. In 28 cases there was at least one known risk factor, the ANSM said.
The agency said that miscarriages were very frequent in the general population (occurring in 12 to 20% of pregnancies, according to studies).
In two recent studies, the ANSM said, researchers had not found a link between miscarriages and mRNA Covid vaccines.
The ANSM earlier said it had received reports of thirty individual-symptom adverse reactions in a foetus or new-born baby.
The agency reported seven cases of premature birth after administration of Comirnaty, two of which were on the day of vaccination and in one case three hours after vaccination. One case occurred the day after vaccination. In two cases the infant died.
The ANSM said in its most recent report had received reports of 395 adverse reactions concerning the mother after administration of Comirnaty, 136 of which it considered to be serious.
The ANSM said it had received reports of 11 cases of intermenstrual bleeding during pregnancy, seven after administration of Comirnaty and four after administration of the Moderna vaccine. In nine of the cases the chronology (the onset of the adverse reaction and its evolution) was “compatible with the vaccine having a role”, the agency said.
At present, a link with Covid vaccination could not be established, the ANSM added, but monitoring would continue.
The agency said in a previous report that, in five cases, the intermenstrual bleeding occurred between 24 and 72 hours after vaccination and, in two cases, it occurred again after the second vaccine dose. There was later improvement in the woman’s condition in five cases, the ANSM said.
There were 58 reports of adverse reactions during pregnancy (105 individual-symptom events) after administration of the Moderna vaccine, the ANSM said. They included 19 miscarriages and five foetal deaths in utero.
On average, the miscarriages occurred 22 days after vaccination (from one to 70 days), the ANSM said. In five cases, there was a known risk factor (age over 35 years, previous miscarriage or infertility treatment). In eight cases, the miscarriage occurred after the first vaccine dose and in 11 cases it occurred after the second dose.
The 78 adverse effects on pregnant women that were reported after administration of the Moderna vaccine included a serious case of pericarditis, which occurred after the first dose, the ANSM added. The woman went to hospital 14 days after vaccination with thoracic pain and tachycardia.
Fifteen reports of adverse reactions during pregnancy (19 individual-symptom events) followed administration of Vaxzevria, the agency said. The 15 cases included nine miscarriages and one ectopic pregnancy. In all cases, the reported adverse reaction occurred after the first vaccine dose.
In all cases, the women were vaccinated before March 19, when it was recommended that the vaccine only be administered to people aged above 55 years.
One case of a thromboembolic adverse reaction during pregnancy has been reported after administration of Vaxzevria. The risk factors were obesity and diabetes.
There have also been 11 reports of thromboembolic adverse reactions after administration of Comirnaty, the ANSM said.
The ANSM said that no safety signals had emerged among pregnant and lactating women for the Covid-19 vaccines available in France. It added, however, that it was closely monitoring the occurrence of thromboembolic events and foetal deaths in utero, painful uterine contractions, intermenstrual bleeding, and cases of HELLP syndrome, which involves haemolysis (the breakdown of red blood cells), elevated liver enzymes, and a low platelet count, and is potentially life threatening. The occurrence of mastitis after Covid vaccination is also being monitored.
The ANSM also says that a link between foetal deaths and Covid vaccination has not been established. Foetal deaths in utero occurred in one to three pregnancies in 1,000 in the general population, the agency said.
The agency also said it had received six reports of HELLP syndrome, but that it lacked clinical data about the cases. The cases occurred after administration of Comirnaty, the women affected were aged between 30 and 40 years, and the adverse reaction occurred up to 24 days after vaccination (in one case the person suffered chest pain and vomiting the night after vaccination and was hospitalised on the 15th day). Five of the cases occurred after the first vaccine dose and one occurred after the second dose.
The ANSM said that, in three of the cases, the time interval between vaccination and the onset of HELLP syndrome was short and this seemed incompatible with the vaccine playing a role. In two cases, there was a HELLP syndrome risk factor, such as obesity or metrorrhagia (abnormal bleeding) at the beginning of the pregnancy.
The agency specified that, in one case, the woman had high blood pressure before vaccination, and there was already a high-risk factor. In another cases, there had been intermenstrual bleeding at the start of the pregnancy and before vaccination.
“HELLP syndrome is a pathology that develops progressively,” the ANSM said. The syndrome occurred in 0.5–0.9% of pregnancies in the general population, the agency added.
The ANSM said there currently did not appear to be a safety signal in relation to the syndrome.
The agency also said there had been 12 reports of serious thrombotic events during pregnancy after Covid vaccination, 11 after administration of Comirnaty and one after administration of Vaxzevria.
The ANSM said that in six of the cases of thromboembolic events there were risk factors other than pregnancy, such as diabetes, hereditary and autoimmune pathologies, and obesity. In three of the cases of pulmonary embolism, the timing of symptom onset seemed to be incompatible with the vaccine being the cause (symptom onset the same or next day in two cases and 37 days after vaccination in one case).
The ANSM said it had received six reports of pulmonary embolism during pregnancy after administration of Comirnaty, four reports of deep vein thrombosis, and one report of cerebral venous sinus thrombosis.
The agency said it had also received reports of eight cases of tachycardia during pregnancy after administration of Comirnaty, four of which it considered to be serious. It also reported six cases of high arterial blood pressure, including four cases that were considered to be serious.
The ANSM also said it had received 29 reports of painful uterine contractions during pregnancy, 24 cases after administration of Comirnaty and five cases after administration of the Moderna vaccine.
The agency said that, in 18 of the cases, the contractions occurred between 30 minutes and 72 hours after vaccination and there was symptom regression within 72 hours in 13 cases. This, the ANSM said, was compatible with a potential role of the vaccine.
The ANSM said a link between the onset of uterine contractions and Covid vaccination could not be established at present but added that “this type of effect must continue be monitored”.
“A study of 539 pregnant women indicated a rate of post-vaccination uterine contractions of 1.3% after the first dose and 6.4% after the second dose,” the agency said. “According to our monitoring, most cases occurred after the first dose.”
The ANSM said it had received 102 reports related to breastfeeding, 86 of which followed administration of Comirnaty. Five followed administration of Vaxzevria and 11 followed administration of the Moderna vaccine. There were 173 individual-symptom events.
Thirty-eight of the cases were medically confirmed and 12 were considered to be serious.
Twenty-four of the reports related to effects on lactation, 42 to effects experienced by the child being breastfed (the age range was one month to two years), and 36 to effects experienced by the mother (77 individual symptoms).
The ANSM said that few of the 33 adverse effects experienced by the mother during breastfeeding were considered to be serious. It also said that 79% of the effects reported that related to the breastfeeding baby were considered not to be serious. Symptom onset ranged from a few hours to 14 days after vaccination of the mother and the most common adverse reactions were gastrointestinal.
In 26 of the cases, the adverse reactions occurred after the mother’s first vaccine dose, in nine cases they occurred after the second dose, and, in six cases, they occurred after both doses. In one case, this information was not available.
The cases cited by the ANSM of reported adverse effects on breastfeeding babies that were reported after administration of Comirnaty included the following:
- A papular rash the day after the mother’s vaccination in a five-year-old infant, whose condition improved within five days.
- Fever of 38,5°C and a skin rash in an infant aged 15 months the day after the child’s mother received her first vaccine dose. The rash persisted, without worsening, for several weeks after the second dose.
- Twelve hours after vaccination of the mother (second dose), a four-month-old infant suffered abdominal pains and slow transit constipation. A four-month-old infant suffered somnolence on the second day after the mother received her first vaccine dose.
- An infant suffered vomiting 12 hours after the mother received her second dose. It lasted for 36 hours.
The ANSM also reported on the case of a woman who was breastfeeding an infant aged one and a half months. The child was hospitalised eight days after the mother received her second vaccine dose because of a failure to gain weight. The child had previously had good weight gain since birth, but, after the mother’s vaccination, lost weight and suffered from asthenia (weakness).
The ANSM had previously reported on the case of a woman breastfeeding a three-month-old infant and suffered mastitis in the hours after each of the two vaccine doses she received. After the first dose the woman recovered within 24 hours, but, after the second dose, her condition worsened after nine days and there was blood in her breast milk.
The agency also previously reported on a decrease in breast milk that was experienced by three women aged between 30 and 34 years. Onset ranged from a few hours to four days after vaccination.
In one case, the adverse reaction occurred after both vaccine doses. Twelve hours after the second dose, the woman reported having the shivers alternating with hot flushes and also delayed milk ejection.
In a previous report, the ANSM cited a case in which there was a serious decrease in the mother’s milk supply and the baby vomited after every feed from the first day after the mother’s vaccination. The mother attempted to breastfeed for ten days, then had to stop.
The ANSM said adverse reactions experienced by babies and children after their mother received a Covid vaccination ranged from skin rashes to gastrointestinal problems. The agency said a link had not been established with Covid vaccination.
The agency also said that it had not established a link between adverse effects on lactation and Covid vaccination and it didn’t consider that there was a safety signal in the case of these reactions. “There does seem to be a predominance of reports about a decrease in milk supply, but information is scant,” the ANSM said.
In a previous report, the agency listed adverse reactions that it described as not serious. They include the following:
- three cases of digestive problems (diarrhoea and vomiting) in breastfeeding babies aged between two and four months, which began between one and two days after the mother’s vaccination;
- fever and walking difficulties for a one-year-old baby five days after his mother received her first vaccine dose;
- changes in the sleep pattern of a two-month-old breastfeeding baby one hour after the mother’s vaccination and again eight hours later (the baby slept deeply for a long time);
- a case of fatigue in a breastfeeding baby the day after the mother’s vaccination; and
- a change in behaviour (the baby becoming very agitated) after the first and second vaccine doses.
In its 2nd report about adverse reactions to Covid vaccination among pregnant and breastfeeding women, which covered data up to June 15, the ANSM said that, in one case of adverse reactions after administration of Comirnaty, the breastfeeding baby had fever and asthenia (abnormal physical weakness or a lack of energy) the day after his/her mother received the Pfizer‐BioNTech vaccine. The mother had experienced injection-site pain, thirst, and muscle pain.
In another case, the baby had skin rashes 48 hours after his/her mother received the Pfizer‐BioNTech vaccine. The mother had experienced injection-site pain and digestive problems.
In one case, the baby had fever 72 hours after his/her mother received Vaxzevria. The mother had experienced flu-like symptoms, dyspnea (shortness of breath), pain in the extremities, and paraesthesia (skin sensations such as burning, numbness, itching, increased sensitivity, or tingling).
In another case, a woman experienced an increase in lactation after receiving Vaxzevria. She also reported fever, fatigue, and pain at the injection site.
In one case after administration of the Moderna vaccine, a woman experienced hyperlactation on the vaccination side of her body (her milk supply doubled) and, in another case, a woman who was vaccinated seven weeks after giving birth found her milk supply progressively diminishing over five days. By day six there was virtually zero lactation.
According to media reports in France on May 1, the lawyer representing the family of a young medical student from Nantes who died ten days after receiving an AstraZeneca-Oxford vaccination says the postmortem “reinforces the hypothesis of a causality link” between the vaccination and the student’s death.
The student is reported to have died from abdominal thrombosis (in the spleen). The report of the postmortem makes no mention of any infection, virus, cancer, or tumour, the lawyer, Etienne Boittin, is quoted as saying.
Boittin is quoted as saying that the postmortem report does not say that the vaccination is the cause of the student’s death, but it eliminates a certain number of possible causes.
The student is reported to have been vaccinated on March 8 and died on March 18.
Two other cases of deaths in France after an AstraZeneca-Oxford vaccination are under investigation by the Paris public prosecutor.
Boittin is reported to be handling litigation in 15 cases of deaths after AstraZeneca-Oxford vaccination, “mostly of people aged under 60 years”.
Local media in France reported earlier that an investigation had been opened into the death of a man in Arles who had received the AstraZeneca-Oxford vaccine the week before he died on March 11. The man’s wife submitted a complaint to the police and a postmortem is reported to have been carried out.
It was also reported that, on February 11, 2021, several hospitals in western France suspended their vaccination campaigns because so many of their staff had to take leave because of adverse reactions after receiving the AstraZeneca vaccine.
At the request of the regional health agency, vaccination resumed at the hospitals the next day, but in a staggered manner.
According to the news website Le Télégramme, between 20 and 25% of the vaccinated hospital staff in Brest had to take time off work because they suffered from high fever and headaches after Covid vaccination and the situation was the same in the hospital at Quimper.
Agence France Presse (AFP) reported that about fifty staff at the Saint-Lô hospital in Normandy were vaccinated on February 10 and, the next day, a proportion of them were ill with fever and nausea.
“It puts us in difficulty when we have whole teams being vaccinated on the same day and 15% of the team has post-vaccination symptoms,” the hospital’s communications officer, Mélanie Cotigny, told AFP.
Other adverse reactions
Reuters reported on January 2, 2021, that the Mexican authorities said they were studying the case of a 32-year-old doctor who was hospitalised after she received the Pfizer-BioNTech vaccine.
The doctor was admitted to the intensive care unit of a hospital in the northern state of Nuevo Leon after she experienced seizures, difficulty breathing, and a skin rash, Reuters reported.
The health ministry said the initial diagnosis was encephalomyelitis, which is an inflammation of the brain and spinal cord.
In its report on February 5, 2021, the Russian state-owned news agency Sputnik gave the doctor’s name: Karla Cecilia Perez. The agency said that previously Perez had experienced allergic reactions to the antibiotics trimethoprim and sulfamethoxazole.
Sputnik News quoted Perez’s brother-in-law Carlos Palestino as saying the family was not insisting that her paralysis was caused by the vaccine. “However, it is necessary to clarify whether it is connected to the inoculation with the vaccine. We are not arguing that it was the reason. There should be a research to confirm it,” Perez was quoted as saying.
Palestino stressed that the doctor’s relatives had decided to draw the attention of the media to what happened to Perez not to discourage people from vaccination but to make sure that Perez would be cared for adequately and that her case would be studied to prevent further incidents.
Covid vaccination at the Advocate Condell Medical Centre in Libertyville, Illinois, was paused after several healthcare workers reported adverse reactions.
Advocate Aurora Health said that four team members at the centre experienced reactions, including tingling and an elevated heart rate, shortly after vaccination. Three of them are now at home and doing well, and one is receiving additional treatment, Advocate Aurora Health said.
“Out of an abundance of caution, we are temporarily pausing vaccinations at Condell, which will allow us time to better understand what may have caused these reactions,” Advocate Aurora Health added. “We have eight other vaccination locations in Illinois and three in Wisconsin and are continuing at those sites as planned with no disruption.”
A nurse at a hospital in Chattanooga, Tennessee, in the US fainted during a press briefing shortly after receiving the vaccine. Tiffany Dover had been talking about her team being among the first to receive the Covid vaccination. She later said she had an underlying health condition that causes her to faint when she experiences pain.
In a strange sequel, there were reports on social media and some websites that Tiffany Dover had died, but the CHI Memorial Hospital dismissed the rumour and posted a video on Facebook showing Dover with other members of staff.
In one case reported under the Yellow Card system in the UK, the person suffered a very severe epileptic seizure following the first dose of the Pfizer-BioNTech vaccine. She had been seizure free (on medication) for more than 15 years. The person tweeted that it took her nearly a week to recover. After a discussion with her doctor, she decided not to have the second dose.
More than 10,000 stories of injury or death after Covid vaccination are told on the ‘they say it’s rare’ website.