This article has been updated. Latest update 4/12/2021.
- The Pfizer-BioNTech, AstraZeneca-Oxford, and Moderna vaccines are being administered under emergency use authorisations in the UK. The UK regulator has also approved use of the Janssen Biotech vaccine under a conditional marketing authorisation.
- The Moderna vaccine and the Covid vaccine developed by the Johnson & Johnson subsidiary Janssen Biotech 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.
- The European Commission has granted conditional marketing authorisations for the Pfizer-BioNTech, AstraZeneca-Oxford, Moderna, and Janssen Biotech vaccines.
- The Therapeutic Goods Administration in Australia has granted the Pfizer-BioNTech, AstraZeneca, and Moderna vaccines provisional approval.
- China’s top drug regulator has granted the Beijing Institute of Biological Products’ vaccine, BBIBP-CorV, conditional marketing approval.
- In India, six Covid vaccines have been approved for restricted emergency use.
- Vaccine manufacturers are seeking strategies to combat virus variants.
- Several countries are giving 3rd Covid vaccine doses as boosters.
- 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.
- AstraZeneca is doing mix-and-match experiments with vaccine doses from other companies.
- Pfizer and BioNTech and Moderna are conducting trials involving children aged 6 months to 11 years. The FDA has authorised emergency use of the Pfizer-BioNTech vaccine for teenagers aged 12 to 15 years and the European Commission has expanded its conditional marketing authorisation for the vaccine to include the same age group.
- There are concerns that there may be disease enhancement with some vaccines.
- Covid vaccination ‘passports’ or certificates have been introduced in numerous countries and regulations limiting access to certain places and facilities to those who have been vaccinated are becoming increasingly widespread.
- There are growing protests against vaccine mandates and the segregation of the non-vaccinated.
Massive Covid vaccination drives are continuing around the world, mostly under emergency use authorisations.
According to the Our World in Data website, more than 8.1 billion Covid vaccine doses have been administered worldwide. About 34.4 million doses are administered every day and 54.9% 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 2.6 million individual case reports of adverse reactions following Covid vaccination, including more than 13,300 deaths.
The global death toll from Covid-19 is now put at more than five million.
Differences in viewpoints about Covid vaccination, and particularly about the implementation of Covid vaccine certificates and the prospect of generalised mandatory vaccination, are causing 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 are becoming increasingly 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 are increasingly making Covid vaccination a requirement for their staff.
There have been demonstrations in numerous countries against vaccine mandates and the restrictions being imposed on the non-vaccinated. In Australia, police have fired on demonstrators with rubber bullets, and protestors and journalists have been injured by tear gas and pepper sprays.
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.
The main efficacy percentages initially vaunted by the front-running manufacturers relate 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-BioNTech 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 British-Swedish pharmaceutical giant AstraZeneca has conducted a clinical trial combining its AZD1222 vaccine, now known as Covid-19 Vaccine AstraZeneca or Vaxzevria, with Russia’s Sputnik V to assess the safety and immunogenicity of the combination.
The Sputnik V team had already tweeted about this in November 2020:
Sputnik V is happy to share one of its two human adenoviral vectors with @AstraZeneca to increase the efficacy of AstraZeneca vaccine. Using two different vectors for two vaccine shots will result in higher efficacy than using the same vector for two shots. #SputnikV
— Sputnik V (@sputnikvaccine) November 23, 2020
The developers of Sputnik V announced in February that trials testing the combination of the AstraZeneca-Oxford and Sputnik V vaccines had begun.
The CEO of Russia’s sovereign wealth fund, the Russian Direct Investment Fund (RDIF), Kirill Dmitriev, had earlier said that the trials would take place in Azerbaijan and the United Arab Emirates and, later on, in Saudi Arabia.
AstraZeneca said: “Both AZD1222 and Sputnik V are adenoviral vector vaccines that contain genetic material of the SARS-CoV-2 virus spike protein. The adenovirus itself is unable to replicate so it can only act as a carrier of genetic material.”
On August 20, the RDIF, AstraZeneca and R-Pharm, an international pharmaceutical company headquartered in Russia, announced preliminary results from a trial in Azerbaijan of the combined use of the AstraZeneca-Oxford vaccine and the single-dose version of Sputnik V, ‘Sputnik Light’, which uses an adenovirus type 26 (rAd26) vector.
The trial in Azerbaijan began in February 2021. The RDIF said that, to date, 64 volunteers had been vaccinated and the enrolment of volunteers was ongoing.
“Preliminary data from the first twenty participants shows antibodies to the SARS-CoV-2 virus spike protein (S-protein) elicited in 100% of cases,” the RDIF said.
“The interim analysis of data has previously demonstrated a high safety profile for the combined use of the vaccines with no serious adverse events or cases of coronavirus infection after vaccination.”
The AstraZeneca vaccine uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein.
When the adenovirus enters vaccinated people’s cells it delivers the spike protein genetic code. The spike protein primes the immune system to attack the SARS-CoV-2 virus if it later infects the body.
On August 11, the RDIF proposed to Pfizer that they start a trial with Sputnik Light as booster. “Delta cases surge in US & Israel shows mRNA vaccines need a heterogeneous booster to strengthen & prolong immune response. #SputnikV pioneered mix&match approach, combo trials & showed 83.1% efficacy vs Delta,” the Sputnik V team tweeted.
The RDIF has co-sponsored mix-and-match trials with Moderna and the Chinese company Sinopharm and is also reported to be set to start a joint trial with CanSino Biologics in China to test a combined regimen of their vaccines.
On August 4, the RDIF announced the initial safety results of the study in Argentina of the immune response and safety of regimens combining Sputnik Light with the AstraZeneca, Sinopharm, and Moderna.
“The data collected by the Ministry of Health of the Buenos Aires province demonstrates that both the combination of Sputnik Light with other vaccines and vaccination with two injections of only Sputnik Light shows a high safety profile with no serious adverse events following the vaccination,” the RDIF said.
Global vaccination drives
In the United States, where Covid vaccination with the Pfizer-BioNTech vaccine began on December 14, 2020, more than 466 million doses have been given so far.
In the UK, where Covid vaccination began on December 8, more than 116 million doses have been administered.
In China, more than 2.5 billion Covid vaccine doses are reported to have been administered. More than 128 million doses are reported to have been administered in Russia.
India started administering Covid vaccinations on January 16 and about 1.26 billion doses have been administered so far.
Brazil started administering the CoronaVac vaccine, developed by the Chinese company Sinovac Biotech, on January 17 and, since then, more than 313 million 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. 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.
At the end of July, 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.
The director of the Ziv Medical Center in Safed, Salman Zarka, told Kan public radio that Israelis now needed to prepare for a fourth Covid vaccine dose, which he said might be modified to better protect against new variants of SARS-CoV-2.
According to Channel 12 news, internal health ministry data shows that 14 Israelis have developed Covid-19 a week after receiving their booster shot. The network said that two of the 14 people had been hospitalised.
A team of Israeli researchers say that their findings indicate 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, Yair Goldberg et al. say that quantifying the effect of waning immunity on vaccine effectiveness is “critical for policy makers worldwide facing the dilemma of administering booster vaccinations”.
They say 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 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, the Pfizer-BioNTech vaccine is, 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 indicates waning protection against SARS-CoV-2 infection, showing just 16% effectiveness against infection transmission among those who received a second dose in January, 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 shows that, among those aged over 65 years, there are 69 serious cases of Covid-19 per million people among those vaccinated and 72 serious cases per million people among the non-vaccinated. It’s also been 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 and restrictions, including school closures, were reimposed. On June 25, 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 June 11, more than 16 million doses had been administered.
Algeria started its Covid vaccination drive on January 30, administering Russia’s Sputnik V vaccine. By September 23, more than 9.9 million doses had been administered.
Egypt began the vaccination of medical staff on January 25, administering the BBIBP-CorV vaccine at a hospital in the northeastern province of Ismailia. By September 23, more than 13.8 million doses had been administered in the country.
On May 13, 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. The country is set to receive a total of 4.5 million doses of the AstraZeneca-Oxford vaccine via the COVAX Facility.
On February 4, 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 after receiving 5,000 doses of the Moderna vaccine from Israel and as of September 23 about two million doses had been administered.
About 320,000 doses of the Pfizer-BioNTech vaccine have been allocated to four African countries – Cabo Verde, Rwanda, South Africa and Tunisia.
The vaccine has received WHO emergency use approval, but requires countries to be able to store and distribute doses at minus 70 degrees Celsius.
The WHO said the aim was to provide up to 600 million vaccine doses to Africa by the end of 2021.
In addition to the vaccines being supplied by the COVAX Facility, the African Union has secured 670 million vaccine doses for the continent that will be distributed in 2021 and 2022 as countries secure adequate financing.
The FDA has now authorised the use of booster doses of the Pfizer-BioNTech, Moderna, and Janssen vaccines.
After earlier authorising the use of Pfizer-BioNTech boosters, the FDA, on October 20, amended the emergency use authorisations (EUAs) for the Moderna and Janssen vaccines to allow for the use of a booster dose, stating the following:
A single booster dose of the Moderna vaccine may be administered at least six months after completion of the primary series to the following people:
- those aged 65 years of age and older,
- 18- to 64-year-olds who are at high risk of developing severe Covid-19, and
- 18- to 64-year-olds who have frequent institutional or occupational exposure to SARS-CoV-2.
The use of a single booster dose of the Janssen Covid-19 vaccine may be administered at least two months after completion of the single-dose primary regimen to people aged 18 years and older, the FDA said.
The FDA also 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 Moderna single booster dose is half of the dose that is administered for a primary series dose.
On November 19, the FDA announced that it had amended the EUAs for both the Moderna and Pfizer-BioNTech Covid vaccines 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.
On September 22, the FDA had amended the EUA for the Pfizer-BioNTech Covid-19 vaccine to allow for the use of a single booster dose, to be administered at least six months after completion of the primary vaccination series, in the following groups of people:
- individuals 65 years of age and older,
- individuals aged 18 to 64 years who are at high risk of severe Covid-19, and
- individuals aged 18 to 64 years whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at high risk of serious complications of Covid-19, including severe Covid-19.
The CDC’s Advisory Committee on Immunisation Practices (ACIP) 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, the director of the CDC¸ Rochelle Walensky, overruled the ACIP’s recommendation and aligned CDC policy with the FDA’s EUA amendment.
The CDC now recommends that the following groups should receive a booster shot of Pfizer-BioNTech’s Covid-19 vaccine at least six months after receiving the second of two doses.
- people aged 65 years and older,
- residents aged 18 years and older in long-term care settings, and
- people aged 50–64 years with underlying medical conditions.
The CDC also said that the following groups may receive a booster shot depending on their individual benefits and risks:
- people aged 18–49 years with underlying medical conditions, and
- people aged 18–64 years who have an increased risk of Covid-19 exposure and transmission because of their occupational or institutional setting.
On September 17, 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.
On August 18, 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, 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 µg 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. The booster dose is to be administered at least six months after completion of the primary vaccination series.
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, Moderna had announced that the FDA approved an update to the EUA for the Moderna Covid vaccine to include a 100 µg 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, the Medicines and Healthcare products Regulatory Agency (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.
The recommendation of the CDC is now that everyone should wear a mask in indoor public settings in areas of “substantial or high transmission” of SARS-CoV-2, regardless of vaccination status. It had previously said that only unvaccinated people needed to wear masks indoors.
On May 13, Rochelle Walensky, had said that anyone who was fully vaccinated could participate in indoor and outdoor activities, large or small, without wearing a mask or physical distancing.
Talking about the change in the CDC’s guidelines about masking, announced on July 27, the director of the National institute of Allergy and Infectious diseases (NIAID), Anthony Fauci, said: “Now that we have a Delta variant, that has changed the entire landscape because when you look at the level of virus in the nasopharynx of a vaccinated person who gets a breakthrough infection with Delta, it is exactly the same as the level of virus in a unvaccinated person who’s infected.”
Fauci says the level of virus in the nasopharynx of a person infected with the Delta variant is a thousand times the level it was with Alpha.
He said on CNN: ” We’re not changing the science … the virus changed.” He said that people should still get vaccinated “to save your life, to prevent you from being hospitalised, prevent you from dying, because the one thing that clearly works very well with this vaccine is that, even with the Delta variant, it prevents you, if you do get infected, from getting severe disease, enough to put you in the hospital”.
Associate professor of neurobiology and bioengineering at Stanford University, Michael Lin, tweeted that, “characteristically”, the CDC was couching its new recommendation with “self-justifying distortions of the science to try to deflect away their slowness to properly comprehend and analyse the data”.
Knowledge of Delta’s two times higher basic reproduction number (R0) was established already, “as was knowledge it could break through full RNA vaccination to not just cause disease but transmit onward”, Lin tweeted.
“So I cannot agree with the statement that ‘Today, we have new science related to the Delta’. Unless CDC defines ‘today’ as 2 months ago, or ‘science’ as observations made only within the US. Science is global, and today should mean today.”
Walensky said on July 30 that the findings of a study about a Covid-19 outbreak in Massachusetts had contributed to the CDC’s new masking recommendation.
The data demonstrated that Delta infection resulted in similarly high SARS-CoV-2 viral loads in vaccinated and unvaccinated people, Walensky said.
“High viral loads suggest an increased risk of transmission and raised concern that, unlike with other variants, vaccinated people infected with Delta can transmit the virus,” she added.
“This finding is concerning and was a pivotal discovery leading to CDC’s updated mask recommendation.”
In a report published by the CDC on July 30, Catherine M. Brown et al. said that, in July 2021, following multiple large public events in a town in Barnstable County, Massachusetts, 469 Covid-19 cases were identified among Massachusetts residents who had travelled to the town from July 3 to 17.
Numerous large gatherings were held in the town, which was not identified in the report, and the events attracted thousands of tourists from across the US.
“Persons with Covid-19 reported attending densely packed indoor and outdoor events at venues that included bars, restaurants, guest houses, and rental homes,” Brown et al. wrote.
On July 3, the Massachusetts Department of Public Health had reported a 14-day average Covid-19 incidence of zero cases per 100,000 persons per day in residents of the town, the researchers said. By July 17, the 14-day average incidence had increased to 177 cases per 100,000 persons per day.
A total 346 (74%) of the reported cases occurred in fully vaccinated people (who had received two doses of an mRNA vaccine or a single dose of the Janssen Biotech vaccine 14 days before exposure).
“Testing identified the Delta variant in 90% of specimens from 133 patients,” Brown et al. said. “Cycle threshold values were similar among specimens from patients who were fully vaccinated and those who were not.”
Vaccination coverage among eligible Massachusetts residents was 69%, the researchers said.
Overall, 274 (79%) of the vaccinated people with breakthrough infection were symptomatic, Brown et al. said. They added that, among five patients with Covid-19 who were hospitalised, four were fully vaccinated. No deaths were reported.
Among those who were hospitalised, the unvaccinated patients and two of those who were vaccinated had underlying medical conditions.
Brown et al. said that Ct values obtained with RT-PCR diagnostic tests might provide a crude correlation to the amount of virus present in a sample and could also be affected by factors other than viral load.
“Although the assay used in this investigation was not validated to provide quantitative results, there was no significant difference between the Ct values of samples collected from breakthrough cases and the other cases,” the researchers said.
“This might mean that the viral load of vaccinated and unvaccinated persons infected with SARS-CoV-2 is also similar. However, microbiological studies are required to confirm these findings.”
Brown et al. added: “Findings from this investigation suggest that even jurisdictions without substantial or high Covid-19 transmission might consider expanding prevention strategies, including masking in indoor public settings regardless of vaccination status, given the potential risk of infection during attendance at large public gatherings that include travellers from many areas with differing levels of transmission.”
Walensky said the CDC’s masking recommendation was updated “to ensure the vaccinated public would not unknowingly transmit virus to others, including their unvaccinated or immunocompromised loved ones”.
In earlier updates about quarantine recommendations, the CDC had said that fully vaccinated people “who meet criteria” would no longer be required to quarantine following exposure to someone with Covid-19.
“Additional considerations for patients and residents in healthcare settings are provided,” the CDC added.
According to CNN, the “criteria” were that the person must be fully vaccinated and at least two weeks must have passed since the second dose (in cases where two doses are required).
CNN quoted the CDC as saying it was not known how long protection lasted, so people who had their last vaccine dose three months or more earlier should still quarantine if they were exposed to a case of Covid-19.
“They also should quarantine if they show symptoms,” CNN quoted the CDC as saying.
The recommendation was criticised as being ill thought out and premature.
@Reuters @CDCDirector @CDCgov THIS IS INADVISABLE AND PREMATURE POLICY:
• New strains will quickly become predominant and lead to increased disease severity
• There is an absence of evidence that vaccines protect from transmission
• We are nowhere near herd immunity pic.twitter.com/o9938sTVIq
— Andre Watson 🧬💊💉🎹 (@nanogenomic) February 11, 2021
On March 8, the CDC had updated its guidelines about what people could and could not do after vaccination.
The guidelines stated at that time that people who had been fully vaccinated could do the following:
- gather indoors with fully vaccinated people without wearing a mask.
- gather indoors with unvaccinated people from one other household (for example, visiting with relatives who all live together) without masks, unless any of those people or anyone they live with has an increased risk for severe illness from Covid-19.
They added that, if a person was around someone with Covid-19, they did not need to stay away from other people or get tested unless they had symptoms. “However, if you live in a group setting (like a correctional or detention facility or group home) and are around someone who has Covid-19, you should still stay away from others for 14 days and get tested, even if you don’t have symptoms,” the CDC added.
While there was literal jubilation in many quarters about the new guidelines, there were also many people who were shocked at the separation of people according to their vaccination status.
One person tweeted: “Vaccinated people can gather, no restrictions. But if you are around unvaccinated, all have to mask & SD. This causes a wedge, leads to division, fear, anger, resentment, and lastly compliance/acceptance.”
The CDC issued its new guidelines despite admitting that they were still learning how effective the Covid vaccines were against SARS-CoV-2 variants, how well the vaccines prevented people from spreading the virus, and how long any protection they offered might last.
On May 1, the CDC transitioned from monitoring all reported Covid-19 vaccine breakthrough infections to investigating only those in patients who are hospitalised or die. It says this is “to help maximise the quality of the data collected on cases of greatest clinical and public health importance”.
The CDC said it would continue to lead studies in multiple US sites “to evaluate vaccine effectiveness and collect information on all Covid-19 vaccine breakthrough infections regardless of clinical status”.
The CDC defines a breakthrough case as “a person who has SARS-CoV-2 RNA or antigen detected on a respiratory specimen collected ≥14 days after completing the primary series of a US Food and Drug Administration (FDA)-authorised Covid-19 vaccine”.
Andre Watson, who is the founder and CEO of the regenerative medicine and pandemic defence biotechnology company Ligandal, based in San Francisco, tweeted in response to the CDC’s decision:
The CDC said that, as of October 12, more than 187 million people in the US had been fully vaccinated against Covid-19 and that, up to that date, it had received reports from 50 US states and territories of 31,895 patients with Covid-19 vaccine breakthrough infection who were hospitalised or died.
In an internal CDC presentation, first reported on by the Washington Post on July 29, the CDC estimated that there were 35,000 symptomatic breakthrough infections per week among fully vaccinated adults in the US.
The CDC says the number of reports of Covid-19 vaccine breakthrough infections it receives are likely to be an undercount of all SARS-CoV-2 infections among fully vaccinated people. “National surveillance relies on passive and voluntary reporting, and data might not be complete or representative,” the CDC said.
Data on patients with vaccine breakthrough infection who were hospitalised or died will be updated regularly. Studies are being conducted in multiple U.S. sites that will include information on all vaccine breakthrough infections regardless of clinical status to supplement the national surveillance.
There is controversy over a statement made in a CDC Morbidity and Mortality Weekly Report that people are considered to be unvaccinated when it has been fewer than 14 days since they received the first dose of a two-dose Covid vaccine series or one dose of a single-dose vaccine, or if no vaccination registry data were available.
This means that if someone is infected by SARS-CoV-2, is hospitalised, or dies within those 14 days they are categorised as unvaccinated. This categorisation has serious implications for cases in which death or illness is caused by a Covid vaccine.
In a report entitled ‘SARS-CoV-2 Infections and Hospitalizations Among Persons Aged ≥16 Years, by Vaccination Status – Los Angeles County, California, May 1–July 25, 2021’ by Jennifer B. Griffin et al., published on August 27, it is stated: “Persons were considered fully vaccinated ≥14 days after receipt of the second dose in a 2-dose series (Pfizer-BioNTech or Moderna Covid-19 vaccines) or after 1 dose of the single-dose Janssen (Johnson & Johnson) Covid-19 vaccine; partially vaccinated ≥14 days after receipt of the first dose and <14 days after the second dose in a 2-dose series; and unvaccinated <14 days receipt of the first dose of a 2-dose series or 1 dose of the single-dose vaccine or if no vaccination registry data were available.”
In its Morbidity and Mortality Weekly Report posted online on May 25, and providing data up to April 30, the CDC said it had received more than 10,000 reports of SARS-CoV-2 infection among people who were fully vaccinated with a Covid-19 vaccine.
As of April 30, 10,262 breakthrough infections were reported to the CDC from 46 US states and territories. A total 6,446 of the cases (63%) occurred in women and the median age of those infected was 58.
Based on preliminary data, 2,725 (27%) vaccine breakthrough infections were asymptomatic, 995 (10%) of the patients were known to be hospitalised, and 160 (2%) of the patients died. Among the 995 hospitalised patients, 289 (29%) were asymptomatic or hospitalised for a reason unrelated to Covid-19. The median age of patients who died was 82 years.
The CDC said that 28 (18%) of those who died were asymptomatic or died from a cause unrelated to Covid-19.
Sequence data were available from 555 reported cases, the CDC said. In 356 cases (64%) the viruses were identified as SARS-CoV-2 Variants of Concern. This included 199 variants (56%) identified as B.1.1.7, 88 (25%) identified as B.1.429, 28 (8%) identified as B.1.427, 28 identified as P.1, and 13 (4%) identified as B.1.351.
The CDC said that, during the surveillance period, SARS-CoV-2 transmission continued at high levels in many parts of the US, with about 355,000 Covid-19 cases reported nationally during the week of April 24–30, 2021.
“Even though FDA-authorised vaccines are highly effective, breakthrough cases are expected, especially before population immunity reaches sufficient levels to further decrease transmission,” the CDC said.
“However, vaccine breakthrough infections occur in only a small fraction of all vaccinated persons and account for a small percentage of all Covid-19 cases (5–8).
“The number of Covid-19 cases, hospitalisations, and deaths that will be prevented among vaccinated persons will far exceed the number of vaccine breakthrough cases.”
The CDC says its findings about breakthrough infections are subject to at least two limitations. “First, the number of reported Covid-19 vaccine breakthrough cases is likely a substantial undercount of all SARS-CoV-2 infections among fully vaccinated persons,” it said.
“The national surveillance system relies on passive and voluntary reporting, and data might not be complete or representative. Many persons with vaccine breakthrough infections, especially those who are asymptomatic or who experience mild illness, might not seek testing.”
Secondly, the CDC said, SARS-CoV-2 sequence data were available for only a small proportion of the reported cases.
In Illinois in the US the Department of Public Health said that, as of July 28, 169 fully vaccinated people had died from Covid-19 or Covid-19 complications and 644 had been hospitalised with the disease. A total 51.13% of the Illinois population had been fully vacccinated, the health department added.
In April, the CDC issued new guidance to laboratories in which it recommended reducing the RT-PCR cycle threshold (Ct) value to 28 cycles for fully vaccinated people being tested for SARS-CoV-2 infection.
In a reverse transcriptase–polymerase chain reaction (RT-PCR) test RNA is converted to complementary DNA (cDNA) by reverse transcription, then the cDNA is amplified (copied) by the polymerase chain reaction.
The result of one PCR cycle is two double-stranded sequences of target DNA, each containing one newly made strand and one original strand. The cycle is repeated numerous times (usually 20–30) as most processes using PCR need large quantities of DNA.
Globally, the accepted cut-off level for the Ct value for SARS-CoV-2 ranges between 35 and 40, depending on instructions from the manufacturers of testing equipment. If the virus is detected at a low Ct value, this means that the viral load is high.
In discussions in India between the Maharashtra government and the Indian Council of Medical Research (ICMR) the ICMR said that lowering the Ct threshold might lead to infections being missed. A benchmark of 35, for instance, meant that more patients would be considered positive than if the benchmark were 24, the ICMR said.
The argument in favour of lowering the Ct threshold is that there will be fewer false positives, but the CDC has been accused of making the change so that there will be fewer reports of vaccine breakthrough cases in the US.
It’s possible, however, that the lower threshold will not influence the number of infections detected using nasal swabs. This is borne out by research conducted by Wenling Wang et al. about the detection of SARS-CoV-2 in different types of clinical specimens.
Wang et al. reported on their research in a letter published on March 11, 2020, on the JAMA Network, published by the American Medical Association.
The researchers found that higher viral loads were found in nasal swab testing than in testing of other specimen types so infections were detected at the lower Ct threshold.
They wrote: “The mean cycle threshold values of all specimen types were more than 30 (<2.6 × 104 copies/mL) except for nasal swabs with a mean cycle threshold value of 24.3 (1.4 × 106 copies/mL), indicating higher viral loads.”
UK study finds high virus levels in vaccinated people infected with Delta
Findings from a study conducted in the UK indicate that, if fully vaccinated people are infected with the Delta variant, they can harbour SARS-CoV-2 virus levels that are as high as those in unvaccinated people infected with Delta.
The study, which was released as a pre-print and has not been peer reviewed, was conducted by researchers from several universities and organisations, including Oxford University, the UK’s Office for National Statistics, and the Department of Health and Social Care. The vaccines studied were the Pfizer-BioNTech, AstraZeneca-Oxford, and Moderna vaccines.
The researchers compared the protection provided by Covid-19 vaccines before and after May 17, 2021, when Delta became the predominant variant in the UK.
Referring to the Pfizer-BioNTech and AstraZeneca-Oxford vaccines, the researchers said that Delta infections after two vaccine doses had similar peak levels of virus to those in unvaccinated people. With the Alpha variant, they said, peak virus levels in those infected post-vaccination were much lower.
“With Delta, infections occurring following two vaccinations had similar peak viral burden to those in unvaccinated individuals,” Koen B. Pouwels et al. wrote. “SARS-CoV-2 vaccination still reduces new infections, but effectiveness and attenuation of peak viral burden are reduced with Delta.”
The researchers said their findings had potential implications for onward transmission risk, “given the strong association between peak Ct and infectivity”. The impact on infectivity to others was unknown, they said, but required urgent investigation.
“A greater percentage of virus may be non-viable in those vaccinated, and/or their viral loads may also decline faster as suggested by a recent study of patients hospitalised with Delta,” they said.
Pouwels said that whilst vaccinations reduced the chance of getting Covid-19, they did not eliminate it. “More importantly, our data shows the potential for vaccinated individuals to still pass Covid-19 onto others, and the importance of testing and self-isolation to reduce transmission risk,” he said.
The researchers analysed 2,580,021 test results from nose and throat swabs taken from more than 384,543 people aged 18 years or older between December 1, 2020, and May 16, 2021, and 811,624 test results from 358,983 people between May 17, 2021, and August 1, 2021.
They said their findings indicated that a single dose of the Moderna vaccine had similar or greater effectiveness against the Delta variant compared to a single dose of the Pfizer-BioNTech or AstraZeneca-Oxford vaccine.
They added that two doses of the Pfizer-BioNTech vaccine were shown to have greater initial effectiveness against new SARS-CoV-2 infections, but this declined faster compared with two doses of the AstraZeneca-Oxford vaccine.
The time between doses was not shown to affect effectiveness in preventing new infections, they added, but younger people were shown to be more protected by vaccination than older people.
The researchers also said that two doses of the Pfizer-BioNTech or AstraZeneca-Oxford vaccine provided at least the same level of protection as having developed Covid-19 through natural infection.
People who were vaccinated after being infected with SARS-CoV-2 had more protection than vaccinated individuals who had not previously contracted Covid-19, they said.
Israeli researchers from Maccabi Healthcare Services and Tel Aviv University published a preprint on medRxiv on August 25 in which they report about natural immunity against SARS-CoV-2 compared to vaccine-induced immunity.
They reported that those studied who had recovered from Covid-19 had superior protection against the Delta variant compared to those who received the Pfizer-BioNTech vaccine.
“This study demonstrated that natural immunity confers longer lasting and stronger protection against infection, symptomatic disease and hospitalisation caused by the Delta variant of SARS-CoV-2, compared to the BNT162b2 two-dose vaccine-induced immunity,” Sivan Gazit et al. wrote.
“Individuals who were both previously infected with SARS-CoV-2 and given a single dose of the vaccine gained additional protection against the Delta variant.”
The researchers conducted a retrospective observational study comparing three groups of people: SARS-CoV-2-naïve individuals who received a two-dose regimen of the Pfizer-BioNTech vaccine, previously infected individuals who had not been vaccinated, and previously infected individuals who had received a single dose of the Pfizer-BioNTech vaccine.
They found that vaccinees who had not been infected with SARS-CoV-2 before vaccination had a 13.06-fold increased risk for breakthrough infection with the Delta variant compared to those previously infected, when the first event (infection or vaccination) occurred during January and February of 2021.
Gazit et al. also found that the increased risk of developing symptomatic Covid-19 disease was also significant.
When infection occurred at any time before vaccination (from March 2020 to February 2021), evidence of waning natural immunity was demonstrated, the researchers said.
They added that, with this timescale, vaccinees who had not been infected with SARS-CoV-2 before vaccination had a 5.96-fold increased risk for breakthrough infection and a 7.13-fold increased risk of developing symptomatic Covid-19 disease.
SARS-CoV-2-naïve vaccinees were also at a greater risk for Covid-19-related hospitalisations compared to those that were previously infected, Gazit et al. said.
They said that the advantageous protection afforded by natural immunity that their analysis demonstrated could be explained by the more extensive immune response to the SARS-CoV-2 proteins than that generated by the anti-spike protein immune activation conferred by the vaccine.
“However, as a correlate of protection is yet to be proven, including the role of B-cell and T-cell immunity, this remains a hypothesis,” they added.
The researchers said their study had several limitations. “First, as the Delta variant was the dominant strain in Israel during the outcome period, the decreased long-term protection of the vaccine compared to that afforded by previous infection cannot be ascertained against other strains,” they wrote.
Secondly, they said, their analysis addressed protection afforded solely by the Pfizer- BioNTech. It did not address other vaccines or long-term protection following a third dose.
“Additionally, as this is an observational real-world study, where PCR screening was not performed by protocol, we might be underestimating asymptomatic infections, as these individuals often do not get tested,” they added.
“Lastly, although we controlled for age, sex, and region of residence, our results might be affected by differences between the groups in terms of health behaviours (such as social distancing and mask wearing), a possible confounder that was not assessed.”
Gazit et al. said that their finding that individuals who were previously infected with SARS-CoV-2 seemed to gain additional protection from a subsequent single-dose vaccine regimen corresponded to previous reports, but they could not demonstrate significance in their cohort.
Transmission of SARS-CoV-2
Andre Watson says Covid vaccines have not been robustly shown to prevent asymptomatic infection, only clinical illness.
“It is assumed that some proportion of individuals who have been vaccinated can still acquire the SARS-CoV-2 virus and may transmit to others without exhibiting symptoms, especially while other individuals are not fully vaccinated, and the rates of transmission and infection can vary significantly between different vaccine modalities and must be further studied.
“The viral loads are substantially reduced in vaccinated individuals, though the efficacy of the vaccines in reducing incidence can be considerably variable depending on the vaccine and the cohorts studied.”
In a briefing document released on December 8, 2020, about the Pfizer-BioNTech vaccine, ahead of the VRBPAC meeting on December 10, the FDA states that “data are limited to assess the effect of the vaccine against transmission of SARS-CoV-2 from individuals who are infected despite vaccination”.
Referring to the efficacy data provided by Pfizer, the FDA said: “At this time, data are not available to make a determination about 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 briefing document states: “Demonstrated high efficacy against symptomatic Covid-19 may translate to overall prevention of transmission in populations with high enough vaccine uptake, though it is possible that if efficacy against asymptomatic infection were lower than efficacy against symptomatic infection, asymptomatic cases in combination with reduced mask wearing and social distancing could result in significant continued transmission.
“Additional evaluations including data from clinical trials and from vaccine use post-authorisation will be needed to assess the effect of the vaccine in preventing virus shedding and transmission, in particular in individuals with asymptomatic infection.”
When asked by NBC’s Lestor Holt, during an interview aired in early December 2020, whether someone could still transmit the virus after vaccination the CEO of Pfizer, Albert Bourla, said the company was not certain about this and it was something that needed to be examined.
Several reports have since been published that are seen to indicate that Covid vaccination can prevent SARS-CoV-2 infection in those vaccinated and therefore reduce virus transmission.
In its Morbidity and Mortality Weekly Report dated April 2, 2021, which was posted online on March 29, the CDC reports on the efficacy of the Moderna and Pfizer-BioNTech Covid vaccines in preventing SARS-CoV-2 infection.
In the study, which was carried out in eight locations in the US, 3,950 health care personnel, first responders, and other essential and frontline workers self-tested weekly for SARS-CoV-2 infection for 13 consecutive weeks from December 14, 2020.
“Under real-world conditions, mRNA vaccine effectiveness of full immunisation (≥14 days after second dose) was 90% against SARS-CoV-2 infections regardless of symptom status,” the CDC said. “Vaccine effectiveness of partial immunisation (≥14 days after first dose but before second dose) was 80%.”
Of the 3,950 participants, 2,479 (62.8%) received both recommended mRNA vaccine doses and 477 (12.1%) received only one dose. A total 62.7% of vaccinated participants received the Pfizer-BioNTech vaccine and 29.6% received Moderna vaccine.
Among the unvaccinated participants, 1.38 SARS-CoV-2 infections were confirmed per 1,000 person-days, the CDC says. Among the fully vaccinated participants, 0.04 infections per 1,000 person-days were reported, and among those who had only received one vaccine dose, 0.19 infections per 1,000 person-days were reported.
161 PCR-confirmed SARS-CoV-2 infections were identified among unvaccinated participants. During the 13 days after the first or second vaccine dose, when immune status was considered indeterminate, 33 PCR-confirmed infections were identified and excluded from the outcome.
Five PCR-confirmed infections were reported in participants 14 days or more after the first dose among those who did not receive their second dose during the study period.
Three PCR-confirmed infections were reported 14 days or more after the first dose and up to receipt of the second dose. Three PCR-confirmed infections occurred in participants who received both vaccine doses (≥14 days after the second dose).
“Estimated adjusted vaccine effectiveness of full immunisation was 90% (95% confidence interval [CI] = 68%–97%); vaccine effectiveness of partial immunisation was 80% (95% CI = 59%–90%),” the CDC said.
The CDC says the findings in its report are subject to at least three limitations. Firstly, it says, vaccine effectiveness point estimates should be interpreted with caution given the moderately wide confidence intervals “attributable in part to the limited number of postimmunisation PCR-confirmed infections observed”.
“Second, this also precluded making product-specific vaccine effectiveness estimates and limited the ability to adjust for potential confounders; however, effects were largely unchanged when study site was included in an adjusted vaccine effectiveness model and when adjusted for sex, age, ethnicity, and occupation separately in sensitivity analyses,” the CDC said.
“Finally, self-collection of specimens and delays in shipments could reduce sensitivity of virus detection by PCR; if this disproportionately affected those who received the vaccine (e.g., because of possible vaccine attenuation of virus shedding), vaccine effectiveness would be overestimated.”
Another report, published in The Lancet on February 18, is about a study conducted in Israel. The researchers studied Covid-19 and SARS-CoV-2 infection and rates in healthcare workers who received the Pfizer-BioNTech vaccine.
They say their data show “substantial early reductions in SARS-CoV-2 infection and symptomatic Covid-19 rates following first vaccine dose administration”.
Sharon Amit et al. studied a retrospective cohort of 9,109 vaccine-eligible healthcare workers, comparing vaccinated versus unvaccinated.
The researchers say that, between 15 and 28 days after the first vaccine dose. they saw an 85% reduction of symptomatic Covid-19 and overall infections were reduced by 75%.
There were 170 SARS-CoV-2 infections among the healthcare workers between December 19, 2020, and January 24, 2021. Ninety-nine of them reported symptoms and were designated as Covid-19 cases. Of the 170 healthcare workers who became infected, 89 were unvaccinated, 78 tested positive after the first dose, and three tested positive after the second dose.
Adjusted rate reductions of SARS-CoV-2 infections were 30% and 75% for days 1–14 and days 15–28 after the first dose, respectively.
The rate reductions for Covid-19 disease were 47% and 85% for days 1–14 and days 15–28 after the first dose, respectively.
Amit et al. say the limitations of their study include its observational nature. They also say that a lack of active laboratory surveillance in the cohort might have resulted in an underestimation of asymptomatic cases.
“Data on vaccine efficacy in preventing asymptomatic SARS-CoV-2 infection are scarce, and our results of rate reductions in SARS-CoV-2 infections, which include asymptomatic HCWs, need further validation through active surveillance and sampling of vaccinated people and unvaccinated controls to ascertain the actual reduction of asymptomatic infection in vaccinated individuals,” the researchers said.
“The early rate reductions seen in HCWs might differ from vaccine efficacy reported in the general population due to their higher exposure risk or due to exposure to more virulent or infectious strains.”
Amit et al. said that early reductions of Covid-19 rates provided support for delaying the second dose in countries facing vaccine shortages, but added: “Longer follow-up to assess long-term effectiveness of a single dose is needed to inform a second dose delay policy.”
Another paper, published as a preprint in The Lancet on February 22, is also about the Pfizer-BioNTech vaccine and reports on the SIREN prospective cohort study carried out among staff working in publicly funded hospitals in England.
A total 23,324 people from 104 hospitals were included in the analysis.
Researchers from Public Health England and Oxford University said the study “demonstrates that the BNT162b2 vaccine effectively prevents both symptomatic and asymptomatic infection in working age adults”.
Victoria Jane Hall et al. said the cohort was vaccinated when the dominant variant in circulation was B1.1.7 and the vaccine demonstrated effectiveness against the variant.
The researchers said that a single dose of the Pfizer-BioNTech vaccine demonstrated effectiveness of 72% 21 days after first dose and 86% seven days after the second dose in the antibody negative cohort.
At the beginning of the follow up period, participants were paced in either the positive cohort (antibody positive or with history of infection) or the negative cohort (antibody negative with no prior positive test).
Participants were asked to complete online questionnaires at enrolment and at fortnightly intervals, capturing data on demographics, symptoms, testing, and household, community, and occupational exposure.
Follow-up started on December 7, 2020, the day before vaccine roll-out began in England, with all participants contributing at least one day of follow-up unvaccinated.
At the start of follow-up, 8,203 participants were assigned to the positive cohort and 15,121 were placed in the negative cohort.
At least one vaccine dose was administered to 20,641 participants by February 5. A total 94% of them received the Pfizer-BioNTech vaccine and 6% received the AstraZeneca-Oxford vaccine.
Two vaccine doses were administered to 8% of participants by February 5 (99.9% of them received the Pfizer-BioNTech vaccine and 0.1% received the AstraZeneca-Oxford vaccine).
There were 977 new infections in the unvaccinated group. In the vaccinated group there were 71 new infections 21 days after the first dose and nine new infections seven days after the second dose.
The researchers said that, with fewer of the cohort vaccinated with the Astra-Zeneca-Oxford vaccine, and the later roll-out resulting in less follow-up time accrued, they were unable to investigate the effectiveness of that vaccine within the study.
Hall et al. said: “We provide strong evidence that vaccinating working age adults will substantially reduce asymptomatic and symptomatic SARS-CoV-2 infection and therefore reduce transmission of infection in the population.
“However, it does not eliminate infection risk completely and therefore personal protective equipment, non-pharmaceutical interventions and regular asymptomatic testing will need to be continued until prevalence of SARS-CoV-2 is extremely low to reduce the risk of transmission in healthcare settings.”
In a preprint published on medRxiv on May 1, Matt D.T. Hitchings et al. report on the effectiveness of the CoronaVac vaccine “in the setting of high SARS-CoV-2 P.1 variant transmission in Brazil”. They studied a cohort of healthcare workers in Manaus, where the P.1 variant accounted for 75% of genotyped SARS-CoV-2 samples at the peak of its epidemic.
The researchers concluded: “Evidence from this test-negative study of the effectiveness of CoronaVac was mixed, and likely affected by bias in this setting. Administration of at least one vaccine dose showed effectiveness against symptomatic SARS-CoV-2 infection in the setting of epidemic P.1 transmission.
“However, the low estimated effectiveness of the two-dose schedule underscores the need to maintain non-pharmaceutical interventions while vaccination campaigns with CoronaVac are being implemented.”
A total 53,176 healthcare workers were studied in the analysis of the effectiveness of at least one vaccine dose and 53,153 were studied in the two-dose analysis.
For the early analysis (at least one vaccine dose), RT-PCR tests were done on 1,752 healthcare workers who reported a symptomatic illness at the time of testing and 904 healthcare workers who did report a symptomatic illness at the time of testing.
Of the 1,823 and 974 tests performed for healthcare workers with and without symptomatic illness, respectively, 564 (31% of 1,823) and 212 (22% of 974), respectively, were positive.
The researchers selected 780 healthcare workers who had undergone a total of 786 RT-PCR tests and established 393 case-control pairs with symptomatic illness. They selected 266 healthcare workers who had undergone a total of 270 RT-PCR tests to establish 135 pairs without symptomatic illness.
Among the 53,153 healthcare workers eligible for the two-dose analysis, 47,170 (89%) received at least one dose of CoronaVac and 2,656 individuals (5%) underwent RT-PCR testing from January 19, 2021 to April 13, 2021. Of 3,195 RT-PCR tests, 885 (28%) were positive.
For the two-dose analysis, the researchers established 418 case-control pairs healthcare workers with symptomatic illness and 138 pairs of healthcare workers without symptomatic illness.
“In the early analysis, vaccination with at least one dose was associated with a 0.50-fold reduction (adjusted vaccine effectiveness, 49.6%, 95% CI 11.3 to 71.4) in the odds of symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the first dose,” the researchers wrote.
“However, we estimated low effectiveness (adjusted VE 36.8%, 95% CI −54.9 to 74.2) of the two-dose schedule against symptomatic SARS-CoV-2 infection during the period 14 days or more after receiving the second dose.”
They added: “A finding that vaccinated individuals were much more likely to be infected than unvaccinated individuals in the period 0-13 days after first vaccination (aOR [adjusted odds ratio] 2.11, 95% CI 1.36-3.27) suggests that among this population of healthcare workers, those at higher risk might take up vaccine earlier, leading to underestimation of its effectiveness.”
In a paper entitled ‘Imperfect Vaccination Can Enhance the Transmission of Highly Virulent Pathogens’, published in PLOS Biology on July 27, 2015, Andrew F. Read et al. say that vaccines that keep hosts alive but allow virus transmission can allow very virulent strains to circulate in a population. Such vaccines are often referred to as “leaky vaccines”.
Read et al. explain that when vaccines prevent transmission, as is the case for nearly all vaccines used for humans, evolution towards increased virulence is blocked.
However, they say, when vaccines leak, allowing at least some pathogen transmission, they can create the ecological conditions that allow “hot strains” to emerge and persist.
“The use of leaky vaccines can facilitate the evolution of pathogen strains that put unvaccinated hosts at greater risk of severe disease,” Read et al. wrote.
“The future challenge is to identify whether there are other types of vaccines used in animals and humans that might also generate these evolutionary risks.”
Read et al. reported on experiments with the Marek’s disease virus in poultry that show that modern, commercial leaky vaccines allow the onward transmission of strains otherwise too lethal to persist.
The immunisation of chickens against the Marek’s disease virus enhanced the fitness of more virulent strains, Read et al. reported.
“Immunity elicited by direct vaccination or by maternal vaccination prolongs host survival but does not prevent infection, viral replication or transmission, thus extending the infectious periods of strains otherwise too lethal to persist,” the researchers wrote.
“Our data show that anti-disease vaccines that do not prevent transmission can create conditions that promote the emergence of pathogen strains that cause more severe disease in unvaccinated hosts.”
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, 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, Cominarty, and the EUA-authorised vaccine that has been administered to date. The licensed vaccine is not yet available. The brand name Cominarty 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 says that, prior to the publication on July 28 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 this year.
“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, he 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 (CMA), 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 European Medicines Agency’s (EMA’s) Committee for Medicinal Products for Human Use (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.
The European Commission has also granted CMAs for the Pfizer-BioNTech, AstraZeneca-Oxford, and Moderna vaccines.
The Therapeutic Goods Administration (TGA) in Australia announced on January 25 that it had granted provisional approval for the Pfizer-BioNTech vaccine BNT162b2 (Cominarty) 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.
The FDA’s emergency use authorisation for Moderna’s mRNA-1273 was issued on December 18 and allows the vaccine to be distributed in the US and to be given to individuals aged 18 years and older.
On February 27, the FDA issued an emergency use authorisation 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 December 4, VigiBase listed 2,642,138 reports of adverse events following Covid vaccination, including 13,383 deaths (listed under ‘General disorders and administration site conditions’).
Of the 2,642,138 reports of adverse events after Covid vaccination listed on VigiBase as of December 4, 140,729 were reports of vascular disorders, 142,872 were reports of cardiac disorders, and 109,271 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 927,740 total adverse event reports after Covid vaccination. The figure relates to reports up to November 26. A total 4,237,551 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 19,532 as of November 26 (8,986 from US states and territories or a location reported as unknown and 10,546 from foreign locations).
A total 13,044 deaths followed administration of the Pfizer-BioNTech vaccine, 4,799 followed administration of the Moderna vaccine, and 1,622 followed administration of the Janssen Biotech vaccine. In 79 cases, the name of the vaccine manufacturer was not specified in the report. (There’s a discrepancy between the 19,532 figure and the latter 19,544 total.)
A total 2,449 of the reported deaths occurred on the same day as vaccination, 2,354 occurred the following day, 414 occurred within seven days, and 1,132 occurred within ten to 14 days.
According to Worldometers.info there had been 806,398 deaths from Covid-19 in the US as of December 3.
In its update on November 30, the CDC said more than 459 million doses of Covid-19 vaccines had been administered in the US up to November 29 and VAERS had received 10,128 reports of death (0.0022%) 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, 512,862 reports (up to November 26 and in all locations) relate to adverse events after administration of the Pfizer-BioNTech vaccine (2,454,291 individual-symptom events), 344,599 refer to the Moderna vaccine (1,453,978 individual-symptom events), 69,582 refer to the Janssen Biotech vaccine (323,377 individual-symptom events), and 2,041 relate to an unknown vaccine manufacturer (9,664 individual-symptom events). There’s a discrepancy between the 927,740 total and this one (929,084).
The total number of reported adverse reactions resulting in permanent disability was put at 30,010. VAERS lists, as of November 26, 22,844 cases after administration of the Pfizer-BioNTech vaccine, 6,907 after administration of the Moderna vaccine, and 1,860 after administration of the Janssen Biotech vaccine. In 74 cases, the vaccine manufacturer was not specified. There’s again a discrepancy in the totals.
As of November 26, VAERS lists 7,265 reports of seizures after Covid vaccination. Some other adverse reactions such as ‘generalised tonic-clonic seizure’ (840), seizure-like phenomena (488), and partial seizures (164), are listed separately.
There were 8,123 reports of a pulmonary embolism and 6,358 reports of thrombosis, with separate listings for specific types of thrombosis, such as deep vein thrombosis (5,484), pulmonary thrombosis (713), and cerebral venous sinus thrombosis (548).
There were 5,409 reports of a cerebrovascular accident, 8,594 reports of sleep disorders, 9,993 reports of herpes zoster, 1,513 reports of blindness, and 2,074 reports of deafness. As of November 26, there were 15,723 reports of tinnitus.
There were also 2,220 reports of spontaneous abortion (miscarriage) and 77 reports of stillbirth, 9,218 reports of heavy menstrual bleeding, 2,401 reports of intermenstrual bleeding, 5,275 reports of irregular menstruation, and 3,059 reports of delayed menstruation.
There were also 5,058 reports of Bell’s palsy listed on VAERS as of November 26, and 1,797 reports of Guillain-Barré syndrome (GBS).
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 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. “
The CDC said in the update to its website on November 30 that, as of November 24, about 268 preliminary reports of GBS had been identified on VAERS after administration of the Janssen Biotech Covid vaccine.
These cases had largely been reported about two weeks after vaccination and mostly in men, many aged 50 years and older, the CDC added.
In a report of the ACIP meeting held on July 22, 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 FDA said in its briefing document for the VRBPAC meeting about the Moderna vaccine: “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.”
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 added in its briefing document: “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: “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), 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. For the event of B-cell lymphoma, an alternative etiology is more likely. An SAE of Bell’s palsy occurred in a vaccine recipient, for which a causal relationship to vaccination cannot be concluded at this time.”
The FDA says 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.”
The Times of Israel reported on January 15 on a survey conducted by the Maccabi health fund of the first 600 people in the country to get their second vaccine dose.
Seventy percent of those surveyed reported some pain at the injection site or such effects as fever, nausea, or dizziness within the first 72 hours after getting the shot. There were 13 reported cases of Bell’s palsy. Three people reported a bitter metallic taste in the mouth, two had breathing difficulties and one person fainted.
According to statistics released by Israel’s health ministry on January 14, 1,127 of nearly two million people vaccinated filed reports about adverse effects, most of which the ministry described as minor. The most common side effects reported were weakness, dizziness, headaches, and fever, the ministry said.
The health ministry found that 82,567 people were infected with SARS-CoV-2 within a week of getting their first vaccine dose and the number dropped to 4,500 after 15 days, The Times of Israel reported.
On November 21, on VigiBase, there were 7,365 cases of Bell’s palsy and 3,746 cases of GBS included in the reports of adverse reactions after Covid vaccination.
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.”
myocarditis and pericarditis
There are 7,646 reports of myocarditis (inflammation of the heart muscle) after Covid vaccination listed in the VAERS data up to November 26 VAERS lists 42 reports of viral myocarditis, five cases of infectious myocarditis, four cases of eosinophilic myocarditis, three reports of autoimmune myocarditis, two cases of septic myocarditis, two cases of immune-mediated myocarditis, two cases of giant cell myocarditis, one case of bacterial myocarditis, one case of hypersensitivity myocarditis, and one case of post-infection myocarditis.
The VAERS data also includes 5,066 reports of pericarditis (inflammation of the tissue surrounding the heart), 48 cases of pleuropericarditis, 39 cases of viral pericarditis, 15 cases of constrictive pericarditis, ten cases of infective pericarditis, two cases of bacterial pericarditis, one case of purulent pericarditis, one case of uraemic pericarditis, and one case of cytomegalovirus pericarditis.
The CDC said in the update to its website on November 30 that, as of November 24, VAERS had received 1,949 reports of myocarditis or pericarditis among people aged 30 years and younger who had received a Covid-19 vaccination.
“Most cases have been reported after mRNA Covid-19 vaccination (Pfizer-BioNTech or Moderna), particularly in male adolescents and young adults,” the CDC said.
“Through follow-up, including medical record reviews, CDC and FDA have confirmed 1,071 reports of myocarditis or pericarditis. CDC and its partners are investigating these reports to assess whether there is a relationship to Covid-19 vaccination.”
The CDC announced on June 10 that it would hold an emergency meeting of ACIP on June 18 to discuss reports of heart inflammation after Covid vaccination, but the meeting was cancelled and the matter was discussed during the ACIP meeting from June 23–25.
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 the ACIP meeting. 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 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 a 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-enrollment 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 occured 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 November 21, on Vigibase, there were 12,136 cases of myocarditis and 9,215 cases of pericarditis 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 Demark’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 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, 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.
The EMA also said the PRAC had 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.
The agency added that, since its marketing authorisation in the EU on January 29, and as of September 2, more than 68.4 million doses of the AstraZeneca-Oxford vaccine had been administered in the EEA.
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 369 cases of GBS after administration of the Janssen Biotech vaccine are listed on VAERS up to November 26.
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, 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 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.”
There are defects in the VAERS and other reporting systems and these flaws are highlighted at length by those who consider that the reporting 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.”
Data from Europe
EudraVigilance lists 1,228,780 adverse reaction reports that relate to the four vaccines authorised for use in Europe.
The database lists 607,283 individual adverse reaction reports up to December 4 for the Pfizer-BioNTech vaccine (tozinameran). Most are from the Netherlands (91,179), followed by Germany (76,850), and France (74,223).
A total 416,188 individual adverse reaction reports up to December 4 are listed for the AstraZeneca-Oxford vaccine, with the most listed in Germany (43,047), followed by the Netherlands (37,730), and France (27,693).
A total 165,883 cases are listed for the Moderna vaccine. Most are from the Netherlands (26,218), followed by Germany (19,243), and France with 16,492.
A total 39,426 (cases are listed for the Janssen Biotech vaccine. Most are from the Netherlands (14,081), followed by Germany with 4,682, and Austria (2,473).
EudraVigilance doesn’t provide an overall total of reported deaths after Covid vaccination or specify the total number of reported deaths after administration of each vaccine.The database provides totals of reported deaths in the case of individual symptoms or symptom categories. In all the categories detailed below, in most of the adverse reaction reports the person vaccinated was female and most of the reports relate to vaccinees in the 18–64 age group.The following statistics are as of October 30 and will be updated shortly.After administration of the AstraZeneca-Oxford vaccine
- Nervous system disorders: 919 deaths; 218,764 adverse reaction reports.
- Respiratory, thoracic, and mediastinal disorders: 708 deaths; 37,287 adverse reaction reports. (The mediastinum is the part of the chest that lies between the sternum and the spinal column, and between the lungs.)
- Vascular disorders: 425 deaths: 26,132 adverse reaction reports.
- Infections and infestations: 381 deaths; 30,910 adverse reaction reports.
- Gastrointestinal disorders: 304 deaths; 101,314 adverse reaction reports.
- Blood and lymphatic system disorders: 239 deaths; 12,857 adverse reaction reports.
- Reproductive system and breast disorders: two deaths; 14,676 adverse reaction reports.
After administration of the Pfizer-BioNTech vaccine
- Nervous system disorders: 1,476 deaths; 210,672 adverse reaction reports.
- Respiratory, thoracic, and mediastinal disorders: 1,605 deaths; 53,167 adverse reaction reports, including 987 cases in the 12–17 age group.
- Vascular disorders: 589 deaths; 32,673 adverse reaction reports.
- Infections and infestations: 1,415 deaths; 46,623 adverse reaction reports.
- Gastrointestinal disorders: 555 deaths; 104,425 adverse reaction reports.
- Blood and lymphatic system disorders: 191 deaths; 33,033 adverse reaction reports.
- Reproductive system and breast disorders: five deaths; 37,882 adverse reaction reports.
After administration of the Moderna vaccine
- Nervous system disorders: 782 deaths; 61,630 adverse reaction reports.
- Respiratory, thoracic, and mediastinal disorders: 839 deaths; 15,953 adverse reaction reports.
- Vascular disorders: 299 deaths; 9,072 adverse reaction reports.
- Infections and infestations: 668 deaths; 12,720 adverse reaction reports.
- Gastrointestinal disorders: 306 deaths; 30,096 adverse reaction reports.
- Blood and lymphatic system disorders: 83 deaths; 7,460 adverse reaction reports.
- Reproductive system and breast disorders: six deaths; 6,871 adverse reaction reports.
After administration of the Janssen Biotech vaccine
- Nervous system disorders: 175 deaths; 18,971adverse reaction reports.
- Respiratory, thoracic, and mediastinal disorders: 192 deaths; 3,319 adverse reaction reports.
- Vascular disorders: 134 deaths; 2,931 adverse reaction reports.
- Infections and infestations: 118 deaths; 3,627 adverse reaction reports.
- Gastrointestinal disorders: 69 deaths; 8,075 adverse reaction reports.
- Blood and lymphatic system disorders: 38 deaths; 907 adverse reaction reports.
- Reproductive system and breast disorders: six deaths; 1,823 adverse reaction reports.
The EMA said on August 11 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 are 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
In its weekly summary of Yellow Card reporting, updated on December 2, the MHRA said that, as of November 24, it had received and analysed 395,049 reports of suspected adverse reactions after Covid vaccination.
A total 238,086 reports related to the AstraZeneca-Oxford vaccine. The total number of listed adverse reactions is 844,212 (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 November 24, 136,582 reports of adverse reactions had been submitted relating to vaccination with the Pfizer-BioNTech vaccine, which was first administered in the UK on December 9, 2020. These include a total of 388,618 suspected reactions.
A total 19,101 Yellow Card reports related to the Moderna vaccine. These include a total of 62,126 suspected reactions. The first report was received on April 7.
For the Pfizer-BioNTech, AstraZeneca-Oxford, and Moderna vaccines the overall reporting rate was about three to seven Yellow Cards per 1,000 doses administered, the MHRA said.
There were 1,280 reports of adverse reactions in which the brand of the vaccine was not specified (3,870 total suspected reactions).
The MHRA has received 1,814 UK reports of people dying shortly after Covid vaccination. There were 1,136 reports of death after administration of the AstraZeneca-Oxford vaccine, 628 after vaccination with the Pfizer-BioNTech vaccine, and 18 after administration of the Moderna vaccine. Thirty-two deaths were reported in cases in which the vaccine brand was unspecified.
The majority of the reports of deaths were about elderly people or people with underlying illness, the MHRA said. Usage of the vaccines had increased, the agency said, and, as such, so had reporting of fatal events with a temporal association with vaccination.
“However, this does not mean that there is a link between vaccination and the fatalities reported,” the MHRA said.
The MHRA said it had provided a review of specific fatal reports in its summaries and added: “The patterns of reporting for all other fatal reports does not suggest the vaccines played a role in these deaths.”
According to Worldometers.info, 145,281 people were reported to have died from Covid-19 in the UK as of December 3.
The MHRA said that, in the week since the previous summary to November 17, it had received a further 2,631 Yellow Card reports relating to administration of the Pfizer-BioNTech vaccine, 985 reports after administration of the Moderna vaccine, 599 reports after administration of the AstraZeneca-Oxford vaccine, and 26 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 50,852,133 people had received their first vaccination in the UK by November 24 and 46,232,258 second doses had been administered.
As of November 24, an estimated 24.9 million first doses of the AstraZeneca-Oxford vaccine and 24.5 million first doses of the Pfizer-BioNTech vaccine had been administered, plus about 24.1 million and 20.8 million second doses of the AstraZeneca-Oxford and Pfizer-BioNTech vaccines respectively.
About 1.5 million first doses and 1.3 million second doses of the Moderna vaccine have also been administered.
As of November 24, an estimated 16,383,575 people had received a third or booster vaccine dose in the UK, the MHRA said.
The agency said it had received 10,460 UK reports of suspected adverse reactions after the reported administration of a booster dose of the Pfizer-BioNTech vaccine.
The MHRA added that it had received 1,575 reports of suspected adverse reactions after the reported administration of a Moderna booster dose, 145 such reports after the reported administration of a booster dose of the AstraZeneca-Oxford vaccine, and 68 such reports in which the brand of the booster dose was not specified.
“Overall, this represents an overall reporting rate of less than one report per 1,000 third or booster doses,” the MHRA said.
“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 mRNAvaccines and it was closely monitoring these events.
The MHRA also said suspected adverse reactions had been reported after the administration of Covid vaccine boosters at the same time as flu vaccines.
The MHRA said that, up to November 24, it had received Yellow Card reports of 427 cases of major thromboembolic events with concurrent thrombocytopenia in the UK following vaccination with the AstraZeneca-Oxford vaccine, including 47 that occurred after the second vaccine dose. The patients were aged between 18 and 93 years. Seventy-four of the patients died, including six who died after the second vaccine dose.
“Of the 427 reports, 215 occurred in females, and 208 occurred in males,” the MHRA said. “The overall case fatality rate was 17%.” In four cases, the sex of the patient was not identified in the report.
Cerebral venous sinus thrombosis was reported in 155 cases (average age 46 years) and 272 patients (average age 54 years) had other major thromboembolic events with concurrent thrombocytopenia.
The overall incidence after first or unknown doses was 15.3 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 said.
The MHRA puts the incidence rate after the first dose at 21.1 per million doses in people aged 18–49 years as compared to 11 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 16.3 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 two 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 2.0 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 8.2 million while an estimated 15.9 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 says that, after a thorough scientific review, it concluded that there was evidence of a likely link between administration of the AstraZeneca-Oxford 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.”
The MHRA said the evidence to date did not suggest that the AstraZeneca-Oxford vaccine caused venous thromboembolism that occurred in the absence of a low platelet count.
Reports of suspected thromboembolic events with concurrent thrombocytopenia (after vaccination with the AstraZeneca-Oxford vaccine) in the UK up to and including November 24.
The MHRA also said that, as of November 24, it had received Yellow Card reports of 28 cases of major thromboembolic events (blood clots) with concurrent thrombocytopenia in the UK following administration of the Pfizer-BioNTech vaccine. Ten 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 November 24, it had received Yellow Card reports of three cases of major thromboembolic events (blood clots) with concurrent thrombocytopenia in the UK after administration of the Moderna vaccine. The three patients were adult males under the age of sixty, the MHRA said.
The MHRA said it had received 1,873 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 243 cases of suspected adverse reactions to the AstraZeneca-Oxford vaccine, six cases following administration of the Moderna vaccine, and eight cases in which the vaccine brand was unspecified.
The agency added that an estimated 2.6 million first doses and 417,500 second doses of the Pfizer-BioNTech vaccine had been administered to under-18s in the UK.
A total 11,500 first doses and 10,000 second doses of the AstraZeneca-Oxford vaccine and 17,800 first doses and 13,600 second doses of the Moderna vaccine had been given to under-18s in the UK, the MHRA said.
MYOCARDITIS AND PERICARDITIS
The MHRA 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.
The agency added that, as of November 24, it had received 450 reports of myocarditis and 341 reports of pericarditis after administration of the Pfizer-BioNTech vaccine as well as four reports of carditis, three reports of viral pericarditis and viral myocarditis, two reports of infective pericarditis, one report of a fatal case of non-infective endocarditis, one report of constrictive pericarditis and one report of streptococcal endocarditis. In one of the cases of myocarditis and one of the cases of pericarditis the patient died.
As of November 24, there had been 161 reports of myocarditis and 192 reports of pericarditis after administration of the AstraZeneca-Oxford vaccine, the MHRA added. There were also eight reports of endocarditis, five reports of viral pericarditis, two reports of bacterial endocarditis, two reports of carditis, two reports of acute endocarditis, and two reports of viral myocarditis, one report of infectious myocarditis and one report of autoimmune myocarditis. In two of the cases of myocarditis the patient died.
There were 103 reports of myocarditis, 59 reports of pericarditis, one report of endocarditis, and one report of hypersensitivity myocarditis 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 both first and second 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 eight reports per million doses of the Pfizer-BioNTech vaccine.
In the case of the Moderna vaccine, the overall reporting rate for suspected myocarditis was 37 per million doses and for suspected pericarditis 21 per million doses.
For the AstraZeneca-Oxford vaccine, the overall reporting rate for suspected myocarditis, including viral myocarditis and infectious myocarditis, was three reports per million doses and for suspected pericarditis, including viral pericarditis, it was four reports per million doses, the MHRA said.
“When the reporting rate is calculated by age group, the reporting rate for suspected myocarditis and pericarditis events 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 AstraZeneca COVID-19 vaccine.”
The MHRA added: “For all vaccines there is a trend for decreased reporting in the older age groups. Pfizer/BioNTech is currently the preferred Covid-19 vaccine for the under- 18s age group in the UK vaccination programme, and for this vaccine there is no indication in the current data that there is an increased reporting rate of suspected myocarditis and pericarditis in this age group compared to young adults.”
Reporting rates per million doses for UK ADR reports of suspected myocarditis and pericarditis associated with Covid-19 vaccines, by patient age and dose, as of November 24.
The MHRA said there were largely similar reporting rates between the first and second doses of the Pfizer-BioNTech and AstraZeneca-Oxford vaccines.
“There is greater variability between first and second dose reporting rates with Moderna however the reporting rate estimates for Moderna may lack precision due to the more limited experience with Moderna in the UK and small numbers of suspected reports,” the agency added. “This introduces more uncertainty into the data.”
The MHRA added: “It is important not to compare the reporting rates between the different Covid-19 vaccines as many factors can influence ADR reporting. These reporting rates may also be subject to change as more experience is gathered in the UK.”
The MHRA said myocarditis and pericarditis happened very rarely in the general population and it was estimated that in the UK there were about sixty new cases of myocarditis diagnosed per million patients per year and about 100 new cases of pericarditis diagnosed per million patients per year.
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 November 24, it had received 463 reports of Guillain-Barré syndrome after administration of the AstraZeneca-Oxford vaccine and 26 reports of a related disease called Miller Fisher syndrome.
As of November 24, the MHRA also received 68 reports of GBS and one report of Miller Fisher syndrome following administration of the Pfizer-BioNTech vaccine and seven reports of GBS after administration of the Moderna vaccine.
The MHRA said it would continue to review cases of GBS reported after the administration of Covid-19 vaccines “to further assess a possible association between Guillain-Barré syndrome and Covid-19 vaccines”, with independent advice from its Vaccine Benefit Risk Working Group.
“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-Oxford 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 14 reports of capillary leak syndrome (a condition in which blood leaks from the small blood vessels into the body) after administration of the AstraZeneca-Oxford 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, the EMA said the PRAC had concluded that people who have previously had capillary leak syndrome must not be vaccinated with the AstraZeneca-Oxford 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-Oxford 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 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 continued to review reports of Bell’s palsy after Covid vaccination “and to analyse them against the number expected to occur by chance in the absence of vaccination (the ‘natural rate’)”.
The agency said the number of reports of facial paralysis received so far was similar to the expected natural rate and did not currently suggest an increased risk following Covid vaccination.
The MHRA said it had received reports of 42,325 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 33,006 individual Yellow Card reports (as each report may contain more than one suspected reaction),” the MHRA said.
This was following the administration of about 50.2 million Covid-19 vaccine doses to women up to November 24, 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.
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 104,000 up to end of September 2021 in England, Scotland and Wales).
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.
“Newly 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 24,000) women who were vaccinated during pregnancy and those who gave birth over the same period and were unvaccinated,” the agency said.
“Likewise, surveillance by Public Health Scotland has found similar rates of perinatal mortality (including stillbirths) amongst (more than 3,800) women who were vaccinated during pregnancy and those who gave birth over the same period and were unvaccinated.”
The MHRA said it had received about 3,500 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.
“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 agency said. “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 administration of 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 ‘flu-like’ illness, headache, chills, fatigue, nausea, fever, dizziness, weakness, aching muscles, and a rapid heartbeat.
REPORTS ABOUT THE ASTRAZENECA-OXFORD VACCINE
The reports about the AstraZeneca-Oxford vaccine include 179,003 nervous system disorders (203 fatal), 13,339 vascular disorders (72 fatal), 7,583 blood disorders (12 fatal), 10,114 cardiac disorders (171 fatal), 14,360 eye disorders, including 302 cases of blindness, and 10,272 ear disorders (one fatal) that include 839 cases of hearing loss, 4,214 cases of tinnitus, and 2,234 cases of vertigo.
The reports also include 79,860 gastrointestinal disorders (14 fatal), 3,125 immune system disorders (five fatal), 101,926 muscle and tissue disorders (one fatal), 28,595 respiratory disorders (134 fatal), 51,978 skin disorders, 17,786 psychiatric disorders (six fatal), 19,139 cases of infection (105 fatal) that include 1,614 cases of herpes zoster, and 19,425 reports of reproductive and breast disorders that include 1,280 cases of vaginal haemorrhage and 489 cases of breast pain. There are 214 reports of a miscarriage.
There are 1,250 reports of a cerebrovascular accident (46 fatal), 177 reports of cerebral haemorrhage (47 fatal), and 153 reports of an ischaemic stroke (seven fatal). The cardiac disorders include 179 reports of cardiac arrest (37 fatal).
There are 697 reports of an anaphylactic reaction (two fatal) and 598 reports of Bell’s palsy (there are also another 354 cases described as facial paralysis).
There are 876 reports of thrombocytopenia (seven fatal), 213 reports of immune thrombocytopenia (one fatal), ten cases of thrombotic thrombocytopenic purpura (TTP), and 1,820 reports of non-site specific thrombosis (38 fatal).
There are 15,419 reports listed of adverse reactions related to menstruation and uterine bleeding, including 4,543 reports of heavy menstrual bleeding, 3,150 cases of delayed menstruation, and 2,222 cases of irregular menstruation.
There are also 417 reports of menopausal effects listed, including 299 cases of postmenopausal haemorrhage.
REPORTS ABOUT THE PFIZER-BIONTECH VACCINE
The reports about the Pfizer-BioNTech vaccine include 66,671 nervous system disorders (66 fatal), 6,135 vascular disorders (15 fatal), 13,226 blood disorders (four fatal), 7,780 cardiac disorders (119 fatal), 6,431 eye disorders, including 123 cases of blindness, and 5,256 ear disorders, including 528 cases of hearing loss, 1,929 cases of tinnitus, and 1,367 cases of vertigo.
The reports also include 35,550 gastrointestinal disorders (18 fatal), 1,957 immune system disorders (two fatal), 45,701 muscle and tissue disorders (two fatal), 16,808 respiratory disorders (53 fatal), 27,121 skin disorders (two fatal), 8,113 psychiatric disorders (one fatal), 9,180 cases of infection (102 fatal) that include 1,368 cases of herpes zoster, and 24,595 reports of reproductive and breast disorders (one fatal) that include 1,459 cases of vaginal haemorrhage and 648 cases of breast pain. There are 383 reports of a miscarriage.
There are 397 reports of a cerebrovascular accident (16 fatal), 47 reports of cerebral haemorrhage (nine fatal), and 53 reports of an ischaemic stroke (two fatal).
There are 484 reports of an anaphylactic reaction (two fatal) and 494 cases of Bell’s palsy (there are also another 378 cases described as facial paralysis).
There are 215 reports of thrombocytopenia (one fatal), 76 reports of immune thrombocytopenia, six cases of TTP, and 414 reports of non-site specific thrombosis (eight fatal).
There are 20,790 reports listed of adverse reactions related to menstruation and uterine bleeding, including 5,129 reports of heavy menstrual bleeding, 4,653 cases of delayed menstruation, and 3,078 cases of irregular menstruation.
There are also 143 reports of menopausal effects listed, including 92 cases of postmenopausal haemorrhage.
AstraZeneca and Janssen vaccines under scrutiny
The PRAC says it has concluded that there is a possible link between the Janssen vaccine and rare cases of venous thromboembolism (VTE).
The committee has 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 will be 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 now recommends that, if an individual has 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 says 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.”
This 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”.
The CDC said that, as of November 24, there had been 54 confirmed reports in the US of people developing TTS after receiving the Janssen Biotech vaccine. More than 16.4 million doses of the vaccine had been administered in the US, the CDC added.
“Women younger than 50 years old especially should be aware of the rare but increased risk of this adverse event,” the CDC said. “There are other Covid-19 vaccine options available for which this risk has not been seen.”
The CDC added: “A review of reports indicates a causal relationship between the J&J/Janssen Covid-19 Vaccine and TTS, a rare and serious adverse event – that causes blood clots with low platelets – which has caused or directly contributed to six confirmed deaths.”
Two confirmed cases of TTS had been reported to VAERS following administration of the Moderna vaccine after more than 437 million doses of mRNA Covid vaccines had been administered in the US, the CDC said, adding that, “based on available data, there is not an increased risk for TTS after mRNA Covid-19 vaccination”.
Research in Germany and Austria
On April 9, 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-titer 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 titer 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 postinfluenza 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 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 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 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, 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, 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 lead 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 weekly safety report about Covid vaccination, published on December 2, the TGA said that, as of November 28, it had received 85,714 reports of adverse reactions after Covid vaccination. This is an increase of 2,413 reports compared with the previous week.
The TGA noted that, as of November 28, 39,106,606 Covid vaccine doses had been administered in Australia.
The administration said that it had received 686 reports of people dying after Covid vaccination. This is an increase of four on the number of deaths reported in the update published on November 25.
The TGA said it considered that nine of the 686 deaths were linked to vaccination. The nine deaths all occurred after a first dose of the AstraZeneca-Oxford vaccine, the TGA said. Eight were cases of thrombosis with thrombocytopenia syndrome (TTS) and one was a case of immune thrombocytopenia (ITP). Six of those who died from TTS were women.
The administration added: “Of the 686 deaths reported to the TGA, over 75% occurred in people aged 65 years and older.”
However, the TGA also said: “A 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.”
As of December 2, there had been 2,021 recorded deaths from Covid-19 in Australia, 909 of which occurred in 2020.
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. 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 the AstraZeneca-Oxford vaccine on June 24 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 the AstraZeneca-Oxford vaccine, now branded as Vaxzevria in Australia. An external Vaccine Safety Investigation Group (VSIG) of clinical experts and consumer representatives, 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 summary that it continues to monitor reports of suspected ITP. It added that, following an investigation by the TGA, the product information for the AstraZeneca-Oxford vaccine had been updated to include a warning about ITP.
The administration said that, as of November 28, it had received 93 reports of suspected ITP after administration of the AstraZeneca-Oxford vaccine.
“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.
“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.”
In Australia, the TGA says, ITP has been reported in fewer than one in 100,000 people who have received the AstraZeneca-Oxford vaccine.
The administration also says it is closely monitoring reports about people aged under 18 years and that, as of November 28, it had received about 2,400 such reports after administration of the Pfizer-BioNTech and Moderna vaccines. This is an increase of about 200 reports compared with the previous week.
The most commonly reported reactions were chest pain, dizziness, headaches, nausea, and fever, the TGA said.
Thrombosis with thrombocytopenia syndrome
The TGA said in its latest summary that two new cases of TTS after administration of the AstraZeneca vaccine had been reported over the previous week, taking the total in Australia to 166 cases.
Of these cases, 144 (82 confirmed and 62 probable) related to a first dose of the vaccine and 22 (six confirmed and 16 probable) related to a second dose, the TGA said.
The TGA said that, in Australia, TTS occurred in about two of every 100,000 people after a first dose. “The risk of TTS after a second vaccine dose appears to be much lower and is estimated to be 0.3 out of every 100,000 people after a second dose,” the TGA added.
The administration added 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.
“Women in younger age groups seem to be slightly more likely to develop these kinds of clots. Australian data indicates that patients aged under 50 years are more likely to be classified as Tier 1 and/or require treatment in intensive care,” the TGA said.
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 said, the risk of dying from TTS after vaccination was about one in a million (people receiving a first dose), “and somewhat less than this when both doses are taken into consideration”.
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.”
Approximately 13.5 million doses of the AstraZeneca-Oxford vaccine had been administered in Australia as of November 28, the TGA said.
The TGA says that TTS cases have most often occurred about two weeks after vaccination, although the time to onset or diagnosis varied.
“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 TGA said in an earlier summary. “It can be difficult to distinguish between normal clots and TTS for these cases and they remain under investigation.”
The TGA also said in an earlier summary 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 administration also said in a previous summary that most cases of TTS had occurred in people aged over 50 years because the AstraZeneca-Oxford vaccine 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 the AstraZeneca-Oxford vaccine for people aged 16 to under 60 years old.Previously it had recommended the Pfizer-BioNTech vaccine in preference to the AstraZeneca-Oxford vaccine 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 the AstraZeneca-Oxford vaccine 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 the AstraZeneca-Oxford vaccine 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 the AstraZeneca-Oxford vaccine in preventing severe Covid-19 “strongly outweigh the risks of adverse effects in all Australians 60 years and above”.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.”
Myocarditis and pericarditis
The TGA said that, as of November 28, said it had received 693 reports of suspected myocarditis (alone or along with pericarditis), including 137 cases in 12- to 17-year-olds.
The administration added that it had received 1,471 reports of suspected pericarditis after administration of the Pfizer-BioNTech vaccine, including 109 cases in 12- to 17-year-olds.
The TGA said it had received 354 reports after administration of the Pfizer-BioNTech vaccine that had been assessed as likely to be myocarditis. A total 102 of these reports related to 12- to 17-year-olds.
“The number of reports of myocarditis is increasing each week, which is expected as the number of vaccine doses given also increases each week,” the TGA said.
“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 also said that 14 of the 37 reports of suspected myocarditis alone or in combination with pericarditis after administration of the Moderna vaccine were in 12- to 17-year-olds.
Seventy-three suspected cases of pericarditis had been reported after administration of the Moderna vaccine and four 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.
“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.
The administration added: “Myocarditis is reported in 1–2 in every 100,000 people who receive Comirnaty (Pfizer), although it is more common in young men and teenage boys after the second dose (6–11 cases per 100,000 doses).”
The TGA said the number of suspected pericarditis after administration of the Pfizer-BioNTech vaccine had decreased since the previous week as cases in which there was both myocarditis and pericarditis were inadvertently included in that week’s report and some cases had been identified as duplicates and were removed.
“Of the cases classified as likely to be myocarditis, most of the patients experienced symptoms within three days of vaccination,” the TGA said. “Around half of the patients were admitted to hospital with nine being treated in intensive care. Most patients treated in hospital were discharged within four days.”
The TGA added: “As we have received limited adverse event reports for Spikevax (Moderna), our analysis of likely myocarditis cases by age and dose focuses on data for the Comirnaty (Pfizer) vaccine. The estimated reporting rates in Australia appear similar to overseas rates.”
The youngest person in Australia whose case has been classified as ‘likely myocarditis’ was 12 years old, the administration added.
The TGA noted that, as of November 28, about 24.4 million doses of the Pfizer-BioNTech vaccine had been administered in Australia.
The TGA said earlier that, in the UK, higher rates of myocarditis and pericarditis had been reported after administration of the Moderna vaccine than after administration of the Pfizer-BioNTech vaccine.
“In some countries, higher rates of myocarditis and pericarditis have been reported with Spikevax (Moderna) than with Comirnaty (Pfizer). Because the number of cases of myocarditis reported after Spikevax (Moderna) in Australia is small, we are not yet able to calculate reliable reporting rates for it or to see any difference in risk between the two vaccines,” the TGA said in its most recent report.
The TGA said the current overall estimated rates (for the entire population) of myocarditis after the administration of the two mRNA vaccines were similar (1.4 cases per 100,000 doses of the Pfizer-BioNTech vaccine versus 1.8 cases per 100,000 doses of the Moderna vaccine).
“However, statistical analysis shows that there is more uncertainty around the reporting rate for Spikevax (likely to be between 1.2 and 2.5 cases per 100,000 doses) than for Comirnaty (likely to be between 1.3 and 1.6 cases per 100,000 doses),” the administration added.
The TGA doesn’t mention this in its summary, but there were, as of November 18, 58 cases of myocarditis and 140 cases of pericarditis listed on the TGA’s public Database of Adverse Event Notifications (DAEN) after administration of the AstraZeneca-Oxford vaccine.
The TGA said in its latest summary that, as of November 28, it had received 156 reports of suspected Guillain-Barré syndrome occurring after administration of the AstraZeneca-Oxford vaccine.
“It is expected that some suspected cases may not be related to vaccination as GBS can occur after common viral infections and some types of gastroenteritis,” the TGA said.
“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. Symptoms to look out for include weakness 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 said, GBS has been reported in about one in every 100,000 people after administration of the AstraZeneca-Oxford vaccine.
The administration said that, “following rigorous investigations by the TGA and other international regulators”, a clear link between GBS and the AstraZeneca-Oxford vaccine had not been established.
“However as a precautionary measure in response to rare cases following vaccination, warning statements about GBS have been added to the Vaxzevria (AstraZeneca) product information,” the TGA added.
There were also 37 cases of GBS listed on the DAEN as of November 18 that are reported to have occurred after administration of the Pfizer-BioNTech vaccine.
The TGA said in a previous report 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 administration said in its report published on October 14 that it had received about 230 reports of asthenia (weakness) after administration of the Pfizer-BioNTech vaccine 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 the Pfizer-BioNTech vaccine 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 said in a previous report that, as of August 22, it had received 481 reports of a menstrual disorder or unexpected vaginal bleeding after Covid vaccination.
A total 322 of the reports followed administration of the Pfizer-BioNTech vaccine, 157 followed administration of the AstraZeneca-Oxford vaccine and, in the case of two of the reports, the vaccine brand was not specified.
“The most commonly reported symptoms were heavy periods, irregular bleeding, bleeding between periods and painful periods,” the TGA said. “Vaginal bleeding in postmenopausal women has also been reported.”
The TGA also said in an earlier summary that it had received more reports of enlarged lymph nodes after administration of the Pfizer-BioNTech vaccine than after administration of the AstraZeneca-Oxford vaccine – 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 the Pfizer-BioNTech and AstraZeneca-Oxford vaccines.
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 the AstraZeneca-Oxford vaccine.
“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 its 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 the AstraZeneca-Oxford vaccine and 43 reports after administration of the Pfizer-BioNTech vaccine. “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 the AstraZeneca-Oxford vaccine 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 the AstraZeneca-Oxford vaccine. 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 the AstraZeneca-Oxford vaccine.
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.”
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 December 2 provides data up to November 18).
The statistics now include data about the Moderna vaccine, which was first administered to Australians on September 22. The TGA said that, as of November 28, about 1.2 million doses of the vaccine had been administered in Australia.
The TGA said in a previous report that, “due to strong public interest in side effects relating to Covid-19 vaccinations”, and improvements in the TGA’s IT systems, the administration was now publishing reports of suspected adverse effects to vaccines and medicines more rapidly.
More than 30,000 additional adverse event reports became visible on the DAEN.
On August 31, however, the TGA announced that the DAEN–medicines section of the database had become unavailable “due to performance issues resulting from a high number of requests”.
The TGA stated on September 16: “Intense public interest in the DAEN has caused intermittent problems with access and the search function. We have now upgraded the DAEN and full functionality is currently being restored.
“We apologise for any inconvenience and would like to reassure the public that these issues have not affected our ability to receive and analyse adverse event reports.”
The unavailability notice is no longer on the DAEN website, and data searches are no longer timing out.
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 following data is up to November 18.
Reports about the AstraZeneca-Oxford vaccine
A total 41,415 reports are listed of adverse reactions following administration of the AstraZeneca-Oxford vaccine (40,748 reported to relate to “a single suspected medicine”). The reports include 410 deaths (this is five more deaths than were reported as of November 11).
In many cases, the reports cite multiple symptoms.
Reports about the Pfizer-BioNTech vaccine
A total 40,789 reports are listed of adverse reactions following administration of the Pfizer-BioNTech vaccine (40,010 reported to relate to “a single suspected medicine”). The reports include 238 deaths.
Again, in many cases, the reports cite multiple symptoms.
There are 1,626 reports on the DAEN of adverse reactions following administration of the Moderna vaccine, which was granted provisional approval by the TGA on August 9. A total 1,595 reports relate to “a single suspected medicine”). One death after administration of the vaccine has been reported to the TGA.
There are 415 reports on the DAEN of adverse reactions after Covid vaccination, including 22 deaths, in which the type of Covid-19 vaccine is not specified. A total 399 of the reports relate to “a single suspected medicine”.
There are 107 reports on the DAEN of miscarriage after Covid vaccination (all vaccines).
The TGA states that “the protective benefits of vaccination against Covid-19 far outweigh the potential risks of vaccination”.
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.
“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
France’s National Agency for the Safety of Medicine and Health Products (the ANSM) said in the status report it published on November 19, which covers the period up to November 11, that, since Covid vaccination began in the country on December 26, 2020, there had been 111,335 reports of adverse reactions, 24% of which it considers to be serious.
The agency doesn’t provide a total figure for the number of reported deaths after Covid vaccination, but a tally of figures given in previous individual reports indicates that there have been at least 1,235.
The ANSM said earlier that there had been 907 deaths reported after administration of the Pfizer-BioNTech vaccine, 227 following administration of the AstraZeneca-Oxford vaccine, and 77 after administration of the Moderna vaccine.
Twenty-four deaths have been reported after administration of the Janssen Biotech vaccine, which was first used in France on April 24 (for people aged 55 years and above).
According to Worldometers.info, 118,653 people were reported to have died from Covid-19 in France as of November 24.
In its report published on November 19, the ANSM said that more than 100,798,500 vaccine doses had been administered as of November 11. Of these, more than 80,710,500 were doses of the Pfizer-BioNTech vaccine, more than 11,240,500 were Moderna doses, more than 7,797,400 were doses of the AstraZeneca-Oxford vaccine, and more than 1,050,000 were Janssen Biotech doses.
A total 3,462 new adverse reaction reports were registered from October 29–November 11, the ANSM said, and 21% of these cases were considered to be serious. More than 1,873, 600 vaccine doses had been administered during that period, the agency added.
The ANSM said 68,001 adverse reactions had been reported after vaccination with the Pfizer-BioNTech vaccine as of November 11 and 26% were considered serious. A total 2,434 of the cases were reported from October 29–November 11 and 22% of these were considered serious.
The agency said that, as of November 11, it had received 27,166 adverse reaction reports relating to administration of the AstraZeneca-Oxford vaccine, 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 371 of the cases were reported from October 29–November 11 and 20% of these were considered serious.
In France, since March 19, the AstraZeneca-Oxford vaccine has only been administered to people aged 55 years and above.
As of November 11, 15,123 adverse reactions had been reported after administration of the Moderna vaccine, 18% of which were considered serious, the ANSM said. A total 601 cases were reported from October 29–November 11 and 17% of these were considered serious.
The ANSM said it had received 1,045 reports of adverse reactions after administration of the Janssen Biotech vaccine, 40% of which were considered serious. A total 56 of the cases were reported from October 29–November 11 and 32% of these were considered serious.
The agency said it had received six reports of suspected Creutzfeldt-Jakob disease after Covid vaccination. Four of the cases were after administration of the Pfizer-BioNTech vaccine, one was after administration of the Moderna vaccine, and one was after administration of the AstraZeneca-Oxford vaccine.
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.
In a special ‘Focus’ report about the Pfizer-BioNTech vaccine, covering data up to November 4, the ANSM said it had received 493 reports of serious adverse reactions among 12- to 18-year-olds after administration of the vaccine. Of these reports, 230 concerned 12- to 15-year-olds.
Vaccination of 12- to 18-year-olds with the Pfizer-BioNTech vaccine began in France on June 15. As of October 28, nearly eight million doses had been administered to children and adolescents in that age group.
The ANSM said it had received reports of 17 cases of facial paralysis in 12- to 18-year-olds after administration of the Pfizer-BioNTech vaccine and 15 reports of convulsions.
There have also been eight cases of immune thrombocytopenic purpura, ten cases of tachycardia, six reports of liver disorders, five cases of pancreatitis, four reports of a pulmonary embolism, and three reports of Guillain- Barré syndrome.
The ANSM reported earlier that, in one case, the 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.
On July 28, France’s National Health Authority (HAS) recommended administration of the Moderna vaccine to 12- to 18-year-olds. As of October 28, more than 465,000 doses had been administered to children and adolescents in that age group, the ANSM said in an earlier report.
In a special ‘Focus’ report about the Moderna vaccine, the ANSM said that, as of November 4, it had received 191 reports of adverse reactions among 12- to 18-year-olds after administration of the Moderna vaccine. Forty-three of the reactions were considered to be serious and 22 of those affected were hospitalised.
In 145 cases, symptom onset was less than 72 hours after vaccination, the ANSM said. The average symptom onset was three days. The agency said that, in 111 cases, the reactions were common, expected and not serious and included malaise at the time of vaccination.
Sixty-six of the cases occurred after the second vaccine dose, and 22 of these cases were serious, the ANSM added.
Adverse reactions reported after booster doses
The ANSM noted in its previous status report that, since August 24, France’s National Authority for Health (HAS) had recommended a booster Pfizer-BioNTech vaccine dose for people aged 65 years and above and those who were at risk of severe Covid-19. Since October 6, boosters have also been recommended for all professionals working with vulnerable people and individuals in the entourage of people who are immunosuppressed.
In its latest ‘Focus’ report about the Pfizer-BioNTech vaccine, the agency said that, as of November 4, it had received reports of 112 adverse reactions after administration of a Pfizer-BioNTech booster dose (seventy of those affected were women and 42 were men and their average age was 81.3 years).
Thirty-nine of the patients were hospitalised and 35 died.
The ANSM said that almost all of the serious adverse reactions after booster doses were in people aged 65 years or older (100 of the 112 reports). The average age of the patients who died was 81.3 years. In two cases, the patients were aged under 65 years, but had serious antecedent medical problems.
The 112 cases included 13 reports of myocarditis and three reports of pericarditis.
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.
The ANSM said in its ‘Focus’ report about the Moderna vaccine that it had received 97 reports of adverse reactions after administration of a third or booster dose of the Moderna vaccine. The average age of those affected was 72.3 years. Forty-five of the cases were considered to be serious. Twenty-two people were hospitalised and three of them died.
In 56 cases, symptom onset was 72 hours or less after 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 its most recent ‘Focus” report 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 of adverse reactions to the Janssen vaccine
The ANSM said in its previous report that it had received five reports of thromboses with thrombocytopenia after administration of the Janssen vaccine. Four 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 previously that it had received two reports of idiopathic thrombocytopenic purpura after administration of the Janssen 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.
The ANSM also said it had received 14 reports of a cerebrovascular accident, 14 reports of cardiac arrhythmia, 11 reports of coronary heart disease, seven reports of hearing disorders, six reports of Guillain-Barré syndrome, five reports of thrombocytopenia, and three cases of limb ischaemia (a sudden lack of blood flow to a limb) after administration of the Janssen vaccine.
In its summary published on October 8, the agency said it had received 21 reports of arterial hypertension, 13 of which were considered to be serious, after administration of the Janssen vaccine. While most of the patients had recovered, the monitoring committee considered that there was a potential safety signal, the ANSM said.
The ANSM also said previously that it had received eight reports of cases of facial paralysis after administration of the Janssen vaccine, seven of which were considered to be serious.
In a special ‘Focus’ report about the Janssen vaccine that includes data up to October 21, the ANSM says it received 84 reports of vaccine failure, including 21 between September 24 and October 21. Seven cases were excluded.
In three cases this was because the positive SARS-CoV-2 test occurred less than 21 days after vaccination. Two reports related to cases of long Covid being aggravated by vaccination. In two cases, the vaccination date was previous to the Janssen vaccine’s authorisation in Europe.
The median time between administration of the Janssen vaccine and vaccine failure was 55 days, the ANSM said.
The ANSM said that, in 73 cases, the vaccine failure was serious (these patients had a median age of 64). Thirteen of the patients died from Covid-19, the agency said. They were aged between 57 and 87 years.
Of the other patients, 59 were hospitalised, including 34 who were taken into intensive care.
The ANSM said in an earlier report that it had received one report of a case of myelitis (inflammation of the spinal cord) in a patient in their fifties 38 days after administration of the Janssen vaccine. The patient was recovering, the agency said.
“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, a disorder causing inflammation and bleeding in the small blood vessels. 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 the AstraZeneca-Oxford vaccine
In an earlier ‘Focus’ report about the AstraZeneca-Oxford vaccine that includes data up to October 21 the ANSM said it had received 142 reports of vaccine failure, 137 of which met the agency’s specific definition. Of these 137 cases, 108 were considered to be serious. Thirteen of the patients died.
The SARS-CoV-2 variant was identified as Delta in fifty cases and Alpha in two cases. the ANSM said. In the other cases, information bout the variant was not provided.
A total 107 patients were hospitalised, including 34 who required intensive care, the ANSM said.
The agency said in an earlier report about the AstraZeneca-Oxford vaccine that it had received 437 reports of a pulmonary embolism, 471 reports of cases of peripheral thrombosis, and 41 reports of hearing loss after administration of the vaccine.
The ANSM added that its monitoring committee had concluded that the cases of hearing loss constituted a potential safety signal.
The agency said it had also received 276 reports of cases of an ischemic stroke, 601 reports of arterial hypertension, 651 reports of mucocutaneous bleeding, 414 reports of reactivation of viral infection, including herpes zoster, 71 reports of facial paralysis, and 15 cases of pancreatitis after administration of the AstraZeneca-Oxford vaccine.
The agency said in its most recent report that it had received reports of 64 cases of “atypical thrombosis” after administration of the AstraZeneca-Oxford vaccine, including 29 reports of vaccine-induced immune thrombotic thrombocytopenia (VITT).
Myocarditis and pericarditis
The ANSM said in its previous report that cases of myocarditis reported in France were the subject of investigation at European and national level and results of a pharmaco-epidemiological study by the French group of scientific experts EPI-PHARE.
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 there was a risk of myocarditis and pericarditis in the seven days after administration of the Pfizer-BioNTech and Moderna vaccines in people aged between 12 and 50 years, and particularly in the under-30s.
EPI-PHARE said the risk was higher with the Moderna vaccine than with the Pfizer-BioNTech vaccine.
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 the Pfizer-BioNTech vaccine, 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 the Pfizer-BioNTech vaccine.)
The ANSM said in an earlier report about the Pfizer-BioNTech vaccine that, as of September 30, it had received 375 reports of myocarditis. The agency previously said that, as of August 28, it had received 299 reports of pericarditis after administration of the vaccine.
The ANSM said in its ‘Focus’ report about the Pfizer-BioNTech vaccine that, as of November 4, it had received 79 reports of reports of myocarditis and 39 reports of pericarditis in 12- to 18-year-olds after administration of the vaccine.
The agency had said earlier that a preliminary analysis indicated that more cases of myocarditis were reported after administration of the Pfizer-BioNTech vaccine 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 is a rare adverse reaction, the ANSM says, and the benefits of the vaccine still outweigh 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 the Pfizer-BioNTech vaccine.
Ten of the cases of myocarditis reported as of September 30 after administration of the Moderna vaccine, and one of the cases of pericarditis, were in 18-year-olds, the ANSM said. In one of the cases of myocarditis, the adolescent was 15 years old.
The ANSM had previously said that one case of pericarditis had been reported after administration of the Janssen Biotech vaccine. Its onset was five days after vaccination and the patient recovered well, the ANSM said.
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 the AstraZeneca-Oxford vaccine.
The ANSM also said in a previous summary that it had received reports of eight cases of Parsonage Turner syndrome after administration of the Pfizer-BioNTech vaccine.
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 also said in an earlier summary that there was a new potential safety signal after 229 cases of menstrual disorders had been reported as of July 27 after administration of the Pfizer-BioNTech vaccine.
The agency said in its summary published on August 6 that it had received 261 such reports, thirty of which related to serious adverse reactions. The median age of the women was 36.5 years (18 to 76 years).
The ANSM added that, as of September 9, it had received 238 reports of serious menstrual disorders after administration of the Moderna vaccine.
In the case of both vaccines, the ANSM said that, in most of the cases, there was improvement in the women’s condition within a few days. “We cannot at this stage conclude that there is a link between vaccination and these menstrual disorders,” the ANSM said. “There could be multiple causes for these disorders.”
Reporting about the administration of the Pfizer-BioNTech and Moderna vaccines, the ANSM said the types of menstrual disorders reported were diverse and included delayed menstruation, intermenstrual bleeding, and heavy bleeding.
In the case of the Pfizer-BioNTech vaccine, most of the problems occurred after the first vaccine dose (177 cases). Fifty-eight cases occurred after the second dose and, in 11 cases, there were problems after both doses.
“These effects, mostly non-serious, but unexpected and occurring also in women after menopause, constitute a potential safety signal,” the ANSM had said earlier.
The agency said the monitoring committee considered there to be a potential safety signal for both the Moderna and Pfizer-BioNTech vaccines and that the ANSM would report that signal to the EMA.
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, nineties, and seventies.
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 the Pfizer-BioNTech vaccine, 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 the AstraZeneca-Oxford vaccine. 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 the Pfizer-BioNTech vaccine. 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 the Pfizer-BioNTech vaccine.
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.
Adverse reactions during pregnancy and breastfeeding
The ANSM has published its 7th monthly pharmacovigilance report about adverse reactions to Covid vaccination among pregnant and breastfeeding women, which provides data up to November 4.
The agency said there had been 426 reports of adverse reactions relating to the period of pregnancy, 293 of which were considered to be serious. There were 17 reported deaths in utero.
Most of the adverse reactions reported in relation to pregnancy occurred after administration of the Pfizer-BioNTech vaccine, 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 359 of the adverse event reports (562 individual-symptom effects) followed administration of the Pfizer-BioNTech vaccine, 52 followed administration of the Moderna vaccine, and 15 followed administration of the AstraZeneca vaccine.
A total 160 of the reported adverse reactions after administration of the Pfizer-BioNTech were miscarriages, 13 were foetal deaths in utero, and two were ectopic pregnancies.
On average, the miscarriages occurred 21 days after vaccination. In 81 cases the miscarriage occurred after the first vaccine dose and, in 64 cases, it occurred after the second dose.
Seventy-seven of the miscarriages occurred within two weeks after vaccination. In 27 cases there was a known risk factor, the ANSM said.
The agency said that there were associated risk factors in 30% of the reported cases of miscarriage after Covid vaccination and 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.
“Miscarriages are very frequent in the general population (occurring in 12 to 20% of pregnancies, according to studies),” the ANSM said.
The ANSM 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 the Pfizer-BioNTech vaccine, 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 also said it had received reports of 368 adverse reactions concerning the mother after administration of the Pfizer-BioNTech vaccine.
The ANSM said it had received reports of 11 cases of intermenstrual bleeding during pregnancy, seven after administration of the Pfizer-BioNTech vaccine and four after administration of the Moderna vaccine.
The agency had said in its 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.
The agency said that four cases of intermenstrual bleeding had been reported after administration of the Moderna vaccine. The bleeding had occurred between two and seven days after vaccination.
The ANSM says that, in nine of the total 11 cases, the chronology (the onset of the adverse reaction and its evolution) were “compatible with the vaccine having a role”, the ANSM said. At present, a link with Covid vaccination could not be established, the agency added, but monitoring would continue.
There were 52 reports of adverse reactions during pregnancy (95 individual-symptom events) after administration of the Moderna vaccine, the ANSM said. They included 17 miscarriages and four foetal deaths in utero.
On average, the miscarriages occurred twenty days after vaccination (from one to 70 days), the ANSM said. In four cases, there was a known risk factor (age over 35 year, previous miscarriage or infertility treatment).
The 71 adverse effects on pregnant women that were reported after administration of the Moderna vaccine included a serious cases 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 the AstraZeneca-Oxford vaccine, 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.
On average, the miscarriages occurred 26.5 days after vaccination (from 13 to 43 days), the ANSM said. In one case, there was a known risk factor (obesity). In seven cases, the miscarriage occurred after the first vaccine dose and in ten cases it occurred after the second dose.
One case of a thromboembolic adverse reaction during pregnancy has also been reported after administration of the AstraZeneca-Oxford vaccine. The risk factors were obesity and diabetes.
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 the 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 the Pfizer-BioNTech vaccine, 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 in an earlier report. The syndrome occurred in 0.5–0.9% of pregnancies in the general population, the agency added.
The ANSM said it did not consider that there was currently a safety signal in relation to the syndrome.
The agency also said there had been 11 reports of serious thrombotic events during pregnancy after Covid vaccination, ten after administration of the Pfizer-BioNTech vaccine and one after administration of the AstraZeneca-Oxford vaccine.
The ANSM said that in six of the 11 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 the Pfizer-BioNTech vaccine, three reports of deep vein thrombosis, and one report of cerebral venous sinus thrombosis.
The ANSM said it had also received reports of eight cases of tachycardia during pregnancy after administration of the Pfizer-BioNTech vaccine, four of which it considered to be serious.
The agency also reported four cases of high arterial blood pressure, including two cases that were considered to be serious.
The ANSM also said it had received 26 reports of painful uterine contractions during pregnancy, 21 cases after administration of the Pfizer-BioNTech vaccine 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 11 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 91 reports related to breastfeeding, 79 of which followed administration of the Pfizer-BioNTech vaccine. Five followed administration of the AstraZeneca-Oxford vaccine and seven followed administrations of the Moderna vaccine. There were 152 individual-symptom events.
Thirty-five of the cases were medically confirmed and 12 were considered to be serious.
Twenty of the reports related to effects on lactation, 38 to effects experienced by the child being breastfed (the age range was one month to two years), and 33 to effects experienced by the mother (73 individual symptoms).
The ANSM said that few of the 33 adverse effects experienced by the mother during breastfeeding were considered to be serious.
The ANSM 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. The most common adverse reactions were gastrointestinal.
In 24 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 four cases, they occurred after both doses. In one case, this information was not available.
The ANSM said that none of the six cases of reported adverse effects on breastfeeding babies that were reported after administration of the Pfizer-BioNTech vaccine were considered to be serious.
The cases cited by the agency 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 said it had received a report of one serious adverse effect on lactation after administration of the Pfizer-BioNTech vaccine.
The case was that 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 the woman’s breast milk.
The ANSM said there had been a decrease in breast milk in 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 its 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 its previous report, the agency lists adverse reactions that it describes 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 the Pfizer-BioNTech vaccine, 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 the AstraZeneca-Oxford vaccine. The mother had experienced flu-like symptoms, dyspnea (shortness of breath), pain in the extremities, and paresthesia.
In another case, a woman experienced an increase in lactation after receiving the AstraZeneca-Oxford vaccine. 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, 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 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, 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.
The UK drugs regulator issued a tender request for the urgent development of an artificial intelligence software tool that can process “the expected high volume” of Covid-19 vaccine Adverse Drug Reactions (ADRs).
The MHRA said in its tender request that it was not possible to retrofit its legacy systems “to handle the volume of ADRs that will be generated by a Covid-19 vaccine”.
The UK government has granted Pfizer legal indemnity protecting the company from being sued by patients in the event of complications following vaccination with BNT162b2.
The new regulation prohibits civil liability against Pfizer or healthcare professionals distributing the vaccine for any damage that arises through use of the vaccine in accordance with specified recommendations.
It will be possible for people to claim a Vaccine Damage Payment. “If you’re severely disabled as a result of a vaccination against certain diseases, you could get a one-off tax-free payment of £120,000,” the UK government states on its website. However, this payment could affect the claimant’s entitlement to such benefits as income support, housing benefit, child tax and pension credits, and the employment and support allowance.
There has been concern in Germany about the lack of data about the efficacy of the AstraZeneca-Oxford vaccine in the older population and the authorities at one stage issued a draft recommendation that it should not be used for those aged 65 years and above.
The Standing Vaccine Commission at Germany’s main public health agency, the Robert Koch Institute, said there were “insufficient data currently available to ascertain how effective the vaccination is above 65 years” and the vaccine should only be offered to people aged 18–64 years.
In the trial of the AstraZeneca-Oxford vaccine, only 341 people aged over 65 received the vaccine, and 319 were given a placebo, the committee said.
However, on March 3, the German Chancellor, Angela Merkel, said the country’s authorities were changing their stance and would allow the vaccine to be administered to those aged 65 and above. Merkel said recent studies had now provided enough data for the vaccine to be approved for all ages.
Merkel also said the German authorities would extend the interval between vaccine doses to offer as many people as possible an initial shot.
Deutsche Welle reported on February 8 that 14 residents at a German nursing home tested positive for SARS-CoV-2 after receiving two doses of the Pfizer-BioNTech vaccine, with their last dose administered on January 25.
Officials in the district of Osnabruck said there was an outbreak of the UK variant of the virus at a nursing home in Belm, DW reported.
A local government spokesperson said the 14 residents tested positive at the end of the previous week. None of them showed serious Covid symptoms, officials said.
In August last year, five scientists from the WHO’s Solidarity Vaccines Trial Expert Group expressed their worries about Covid vaccine fast tracking.
The scientists said in a commentary published in The Lancet that deployment of a “weakly effective” vaccine could actually worsen the Covid-19 pandemic.
“There is a danger that political and economic pressures for rapid introduction of a Covid-19 vaccine could lead to widespread deployment of a vaccine that is in reality only weakly effective (e.g. reducing Covid-19 incidence by only 10–20%), perhaps because of a misleadingly promising result from an underpowered trial,” the scientists said.
“Deployment of a weakly effective vaccine could actually worsen the Covid-19 pandemic if authorities wrongly assume it causes a substantial reduction in risk, or if vaccinated individuals wrongly believe they are immune, hence reducing implementation of, or compliance with, other Covid-19 control measures.”
The five researchers said regulators should follow the WHO recommendation that “successful vaccines” should show an estimated risk reduction of at least one-half, with sufficient precision to conclude that the true vaccine efficacy is greater than 30%.
BMJ reporter reveals allegations of bad practice during Pfizer vaccine trial
Investigative journalist Paul Thacker reported in The BMJ on November 2 that an employee of the Ventavia Research Group in the US told him that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase 3 trial.
Thacker reported that Brook Jackson, who was a regional director, repeatedly notified Ventavia of these problems then emailed a complaint to the FDA.
“Ventavia fired her later the same day,” Thacker reported. “Jackson has provided The BMJ with dozens of internal company documents, photos, audio recordings, and emails.”
Since Jackson reported problems with Ventavia to the FDA in September 2020, Pfizer has hired the company as a research subcontractor on four other vaccine clinical trials (Covid-19 vaccination for children and young adults, and for pregnant women, studies of booster dosing, and an RSV vaccine trial), Thacker wrote.
Thacker says Jackson told him that, during the two weeks that she was employed at Ventavia in September 2020, she repeatedly informed her superiors about poor laboratory management, patient safety concerns, and data integrity issues.
“Exasperated that Ventavia was not dealing with the problems, Jackson documented several matters late one night, taking photos on her mobile phone,” Thacker wrote.
“One photo, provided to The BMJ, showed needles discarded in a plastic biohazard bag instead of a sharps container box,” Thacker reported.
“Another showed vaccine packaging materials with trial participants’ identification numbers written on them left out in the open, potentially unblinding participants. Ventavia executives later questioned Jackson for taking the photos.”
In her email to the FDA Jackson wrote that Ventavia had enrolled more than 1,000 participants at three sites in the US. She listed a dozen concerns that she said she had witnessed, including the following:
- participants being placed in a hallway after vaccination and not being monitored by clinical staff,
- a lack of timely follow-up of patients who experienced adverse events,
- protocol deviations not being reported,
- vaccines not being stored at proper temperatures,
- mislabelled laboratory specimens, and
- targeting of Ventavia staff for reporting such problems.
“Within hours Jackson received an email from the FDA thanking her for her concerns and notifying her that the FDA could not comment on any investigation that might result,” Thacker reported.
“A few days later Jackson received a call from an FDA inspector to discuss her report but was told that no further information could be provided. She heard nothing further in relation to her report.”
Thacker added: “In Pfizer’s briefing document submitted to an FDA advisory committee meeting held on 10 December 2020 to discuss Pfizer’s application for emergency use authorisation of its Covid-19 vaccine, the company made no mention of problems at the Ventavia site. The next day the FDA issued the authorisation of the vaccine.”
He reports that Jackson told The BMJ that drug assignment confirmation printouts were being left in participants’ charts, accessible to blinded personnel. “As a corrective action taken in September, two months into trial recruitment and with around 1000 participants already enrolled, quality assurance checklists were updated with instructions for staff to remove drug assignments from charts,” Thacker wrote.
He says that two former Ventavia employees, who spoke to him anonymously, “confirmed broad aspects of Jackson’s complaint”.
One of the employees, who told The BMJ that she had worked on more than four dozen clinical trials, said she had never experienced such a “helter skelter” work environment as with Ventavia on Pfizer’s trial, Thacker reported.
The same employee told The BMJ that, in several cases, Ventavia lacked enough employees to swab all trial participants who reported Covid-like symptoms, to test for infection, he added.
An FDA review memorandum released in August 2021 states that, across the full trial, swabs were not taken from 477 people with suspected cases of symptomatic Covid-19, Thacker added.
The second employee told The BMJ that the environment at Ventavia was unlike anything she had experienced in her twenty years doing research, Thacker wrote.
“She told The BMJ that, shortly after Ventavia fired Jackson, Pfizer was notified of problems at Ventavia with the vaccine trial and that an audit took place,” he added.
Contaminated vials in Japan
In Japan, the use of about 1.62 million doses (three lots) of the Moderna vaccine that were manufactured by Laboratorios Farmacéuticos ROVI in Spain was halted after vials in one lot were found to be contaminated.
Japan’s Ministry of Health, Labour, and Welfare said on August 26 that a foreign substance had been detected in 39 unused vials at eight vaccination sites in five prefectures. This was later found to be particles of stainless steel.
Moderna and the authorised distributor of the vaccine in Japan, Takeda, said that the problems that prompted the suspension of use of the vaccine doses were isolated to one specific lot, but three lots manufactured in the same series were included in the suspension by the ministry “out of an abundance of caution”.
The ministry also said that two men had died after being given a dose of the Moderna vaccine that was from one of the batches whose use was suspended (the doses were not from the vials that were found to be contaminated).
The two men, aged in their thirties, died within days of receiving their second vaccine doses. No foreign matter was found in either of the vials of vaccine used to vaccinate the two men, the ministry said.
Takeda and Moderna said on September 1 that the contamination in the vaccine vials had been found to be particles of high-grade 316 stainless steel, which is commonly used in manufacturing and food processing.
The companies said the most probable cause of the contamination was friction between two pieces of metal installed in the stoppering module of the production line, which was due to an incorrect set-up.
They said the two pieces were the star-wheel and the piece that feeds stoppers into the star-wheel. They companies think the problem occurred during assembly prior to production of batch 3004667 “and was a result of improper alignment during a line changeover before starting this batch”.
Takeda said it planned to recall the three suspended lots (3004667, 3004734, and 3004956) from the market as of September 2, 2021.
ROVI said its investigation showed that the manufacturing problem only impacted the three lots whose use was suspended.
Moderna and Takeda said the “rare presence” of stainless steel particles in the Moderna vaccine did not pose an undue risk to vaccinees and did not adversely affect the benefit/risk profile of the product.
“Metallic particles of this size injected into a muscle may result in a local reaction, but are unlikely to result in other adverse reactions beyond the local site of the injection,” the companies said.
“Stainless steel is routinely used in heart valves, joint replacements and metal sutures and staples. As such, it is not expected that injection of the particles identified in these lots in Japan would result in increased medical risk.”
The companies added; “At this time, there is no evidence that the two tragic deaths following administration of the Moderna Covid-19 vaccine (from lot 3004734) were in any way related to administration of the vaccine.
“The relationship is currently considered to be coincidental. It is important to conclude a formal investigation to confirm this. The investigation is being conducted with the greatest sense of urgency, transparency and integrity and is of the highest priority.”
The companies said earlier that they had not received any product quality complaints about particulate matter in lot 3004734.
On August 28, the Okinawa prefectural government said it had found foreign matter in vials of Moderna’s Covid vaccine. The vials did not come from one of the batches already suspended from use.
The Ministry of Health, Labour, and Welfare said foreign substances were also found in syringes filled with the vaccine. The ministry said it was highly probable that the contamination was caused by part of the rubber stopper on the vial lids or that there was a foreign substance on the syringe.
According to the ministry, the contamination did not originate from the vaccine in unused vials.
Vaccinating children and adolescents
On November 2, the CDC director Rochelle Walensky endorsed the recommendation from the CDC’s Advisory Committee on Immunization Practices (ACIP) that children aged five to 11 years receive the Pfizer-BioNTech Covid vaccine.
Two doses of 10 µg will be administered three weeks apart (30 µg doses are used for people 12 and older). This is 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 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 milion 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 is authorised and recommended by the CDC’s Advisory Committee on Immunisation Practices (ACIP), it will 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 European Medicines Agency.
Pfizer added that initial data from the other two age cohorts in the ongoing Pfizer-BioNTech clinical trial in children – those aged two to under five years and those aged six months to under two years – were expected as soon as the fourth quarter of 2021 or early in the first quarter of 2022.
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 September 14, Pfizer’s chief financial officer, Frank D’Amelio, said the company expected to apply in November for FDA emergency use authorisation for its Covid-19 vaccine for children aged between six months and five years.
On September 20, Pfizer and BioNTech announced results of a phase 2/3 trial of use of their Covid vaccine for children aged five to 11 years. The companies said the vaccine was “safe, well tolerated and showed robust neutralising antibody responses”.
In the trial, two doses of 10 µg were administered 21 days apart (30 µg doses are administered to people aged 12 and above).
“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 10 µg dose was carefully selected as the preferred dose for safety, tolerability and immunogenicity in children five to 11 years of age.”
The data provided from the study, which has been enrolling children aged between six months and 11 years, related to 2,268 participants aged between five and 11 years.
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 titer (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 µg 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.
The phase 1/2/3 trial initially enrolled up to 4,500 children, aged between six months and 11 years, in the US, Finland, Poland, and Spain. It was designed to evaluate the safety, tolerability, and immunogenicity of the Pfizer-BioNTech vaccine in three age groups: five to 11 years; two to five years, and six months to two years. Children aged under five received two 3 µg doses.
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.
On November 25, the EMA announced that the CHMP had recommended granting an extension of indication for the Pfizer-BioNTech vaccine to include use for children aged five to 11 years.
The dose would be lower than that used for people aged 12 years and above (10 µg compared with 30 µg) and there would be two vaccinations, three weeks apart.
The EMA said the CHMP would send its recommendation to the European Commission, which would make a final decision.
On July 23, the EMA announced that its human medicines committee had recommended authorisation of use of the Moderna vaccine (Spikevax) for children and adolescents aged 12 to 17 years. The vaccination would be given in two doses, four weeks apart.
The EMA said effects of the vaccine had been investigated in an ongoing 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.
June Raine said it was for the JCVI to advise on whether that age group should be vaccinated with the Moderna vaccine.
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 May 10, the FDA expanded the emergency use authorisation for the Pfizer-BioNTech vaccine to include adolescents aged 12 to 15 years. 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 μg 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 µg, 20 µg, and 30 µg) with an option for 3 µg, in three age groups (five to 11 years, two to five years, and six months to two years.
The trial started with 144 participants. “Once tolerability is confirmed with the 10 µg within the five- to 11-year-old group, we will progressively move to the next higher dose in the age group, while also starting the following age group (two- to five-year-olds) at the lowest dose (10 µg),” Pfizer said. “This escalation approach will be followed for all doses and age groups.”
In the US, at Stanford Medicine in California, which includes the Stanford University School of Medicine and Stanford Health Care, researchers have started to vaccinate children aged two to five years.
Pfizer said the Phase 2/3 part of the trial would evaluate the safety, tolerability, and immunogenicity of the selected dose level in each age group. Participants would be randomised in a 2:1 ratio to receive the vaccine or a placebo. The vaccine will be administered in a two-dose schedule, with the doses given about 21 days apart.
Throughout the full trial, about 4,644 children would be enrolled in the US and Europe, Pfizer said.
At the six-month follow-up visit, all participants would be unblinded and those who originally received a placebo would be given the opportunity to receive BNT162b2.
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.
If safety and immunogenicity was confirmed, and pending agreement with and endorsement from regulators, Pfizer and BioNTech said they hoped to receive authorisation for vaccination of younger children by early 2022.
“Pfizer and BioNTech expect to have definitive readouts and, subject to the data generated, submit for an EUA or a variation to Conditional Marketing Authorisations for two cohorts, including children two–five years of age and five–11 years of age, in September,” Pfizer said on May 10. “The readout and submission for the cohort of children 6 months to 2 years of age are expected in the fourth quarter.”
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 are also planning studies to further evaluate their vaccine in people with compromised immune systems.
On July 23, 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, 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.
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 say a small number of children have 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 can make children very unwell and some have suffered multi-organ failure, the researchers say, adding that the number of children affected by the syndrome in the first wave of Covid -19 was fewer than one hundred.
On March 16, Moderna announced that the first participants in a trial to test its vaccine on children had received their initial doses. The company says it expected to enrol 6,750 children aged between six months and 11 years in the “KidCOVE” study in Canada and the US.
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 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, 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.
Countries are increasingly introducing regulations that allow those who have received Covid vaccination access to certain places and facilities, such as indoor dining in restaurants, and deny such access to those who have not been vaccinated or cannot show proof of recovery from Covid-19 or a recent negative SARS-CoV-2 test.
There have been demonstrations in Canada and the US and in Israel, France, Spain, Austria, Britain, Switzerland, Italy, Ireland, the Netherlands, Portugal, Luxembourg, Greece, Romania, and Croatia. Australia has been the focus of international attention because of the harsh crackdown on protests in Melbourne, where hundreds of demonstrators have been arrested.
Austria is also under the spotlight as the government introduced lockdown restrictiosns specifically for the unvaccinated. It then extended the restrictions to the whole population and there are reports that Covid vaccination will be made mandatory in the country.
The introduction in Australia of mandatory vaccination for construction workers sparked the latest protests.
In Greece, citizens over the age of 60 have been told to book their appointment for a first Covid vaccination by January 16. Those who fail to comply will be fined €100 a month and will risk jail if they don’t pay.
The measure is still to be put to a parliamentary vote, but lawmakers are expected to approve it.
On August 3, the mayor of New York, Bill de Blasio, announced that access to indoor dining, indoor fitness facilities, and indoor entertainment facilities is to be restricted – in the case of workers and customers – to those who have 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 coming 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 argues that the new policy will 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, 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 has been widespread outrage in France over the country’s new ‘pass sanitaire’. There are plans, for example, to limit hospital visiting to those who have received Covid vaccination, have recovered from Covid-19, or have recently tested SARS-CoV-2 negative.
People in France wanting to go to events or places where there are more than fifty people already have to present a ‘pass sanitaire’ (there is an exemption for 12- to 17-year-olds), and the regulation is due to be extended in August to restaurants, cafés, trade shows, long-distance travel on public transportation, and entry to medical establishments, except for emergencies. It may also be required in large shopping centres.
In Montelimar, hospital staff began an indefinite strike in protest against compulsory Covid-19 vaccination.
In Israel, since October 3, there have been new rules governing who is eligible for the country’s ‘green pass‘, which is only valid for up to six months from the date of the last vaccination. All passes issued prior to October 3 are now void.
The pass is now given, one week after the day of the last vaccination, to those who have received two or three Covid vaccine doses and is valid for up to six months from the date of the last vaccination.
People who have recovered from Covid-19 and hold a certificate of recovery with a positive PCR test result are also eligible for the pass.
People who have recovered once or twice from Covid-19 and have not been vaccinated are eligible for a pass valid for up to six months from the date of the last certificate of recovery.
Those who have recovered and have received one vaccine dose before or after recovery are eligible for a pass valid until March 31, 2022.
Recovered children who are 12 years and three months of age or younger are eligible for a pass that is valid until March 31, 2022, or until they reach the age of 12 years and three months, whichever is later.
Those who have recovered and subsequently tested positive on a serologic test, have never been vaccinated before testing, and, after testing, received at least one Covid vaccine dose are eligible for a pass that will be valid until December 31, 2022.
Children aged 12 years and three months or younger who test positive on a serologic test are eligible for a pass that is valid until December 31, 2022, or until they are 12 years and three months old, whichever is later.
Rules for temporary passes:
Adults and children with a negative privately funded PCR test result can request a daily pass, which is valid for 72 hours from the testing day.
Children three years of age or younger and children aged 12 years and 3 months or younger who have a disability certificate are exempt.
Israel introduced its ‘green pass’ in February. The system expired on June 1, but was later reinstated.
The health ministry announced on August 29 that, as of October 1, 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, has accused those who are eligible to get vaccinated but have 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.
IBM has 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.”
The World Economic Forum and the Swiss nonprofit public trust the Commons Project have been testing CommonPass, a platform for documenting people’s Covid-19 status, including information about PCR tests and Covid vaccination.
Denmark’s government has said that it plans to introduce a digital passport that will indicate citizens’ Covid vaccination status.
In Spain the Tourism Minister, Reyes Maroto, announced that the government was working to introduce a Covid vaccination certificate.
On January 21, Iceland became 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 has also 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 says it will recognise all Covid-19 vaccination certificates that will be issued by EEA/EFTA countries.
According to Schengenvisainfo.com travellers who hold a document that proves they have received a Covid vaccination in any of these countries will be exempt from official border control measures when entering Iceland and will therefore not be obliged to go through border screening procedures.
On June 1, 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 has 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 EU certificate was proposed by the Commission to resume safe travelling this summer,” the EC said. “It will be free of charge, secure, and accessible to all.
“The certificate can be used across all EU member states as well as in Iceland, Liechtenstein and Norway. Contacts are also ongoing to enable its use with Switzerland.”
The EC says the gateway provides 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.”
Certificates will be issued to any person who received a Covid-19 vaccination in an EU member state, irrespective of the number of doses. “The number of doses will be clearly stated in the EU Digital Covid certificate to indicate whether the vaccination course has been completed,” the EC said.
The EC added: “National authorities are in charge of issuing the certificate. It could, for example, be issued by test centres or health authorities, or directly via an eHealth portal.
“The digital version can be stored on a mobile device. Citizens can also request a paper version. Both will have a QR code that contains essential information, as well as a digital signature to make sure the certificate is authentic.
Member states have agreed on a common design that can be used for the electronic and paper versions to facilitate the recognition.”
The EC says the certificate contains 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”.
The commission says 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, 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.
WHO spokesperson Margaret Harris said on April 6 that the WHO was saying it would not like to see vaccination passports as a requirement for entry or exit “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.
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 4 nanometers 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 have been trialling 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, Christine Kellett quoted the Minister for Government Services, Stuart Robert, as saying it is “highly likely” that vaccination certificates will 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 that, from February 1, 2022, it will require customers travelling on its international network to be fully vaccinated.
“It’s not just customers who will be required to be vaccinated – it’s everyone on board an Air New Zealand aircraft travelling internationally,” the airline said.
“Air New Zealand’s vaccination requirement will apply to all passengers aged 18 and older arriving or departing Aotearoa on an Air New Zealand aircraft. Customers who are not vaccinated will be required to present proof that vaccination was not a viable option for them for medical reasons.”
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.
Clampdown on social media
Facebook and YouTube have stepped up their clampdown on what they consider to be misinformation about Covid-19 and vaccines.
YouTube has expanded its policy of removing content it considers to be misleading to include all vaccines.
“Specifically, content that falsely alleges that approved vaccines are dangerous and cause chronic health effects, claims that vaccines do not reduce transmission or contraction of disease, or contains misinformation on the substances contained in vaccines will be removed,” the company stated.
“This would include content that falsely says that approved vaccines cause autism, cancer or infertility, or that substances in vaccines can track those who receive them. Our policies not only cover specific routine immunisations like for measles or Hepatitis B, but also apply to general statements about vaccines.”
YouTube added: “These policy changes will go into effect today, and, as with any significant update, it will take time for our systems to fully ramp up enforcement.”
The company said that, “given the importance of public discussion and debate to the scientific process”, it would continue to allow content about vaccine policies, new vaccine trials, “and historical vaccine successes or failures”.
YouTube added: “Personal testimonials relating to vaccines will also be allowed, so long as the video doesn’t violate other community guidelines, or the channel doesn’t show a pattern of promoting vaccine hesitancy.”
The company has deplatformed the well-known American osteopathic physician and author Joseph Mercola and Children’s Health Defense.
Mercola said: “We are united across the world, we will not live in fear, we will stand together and restore our freedoms.”
Kennedy (pictured below) said: “Free speech is the essential core value of liberal democracy. All other rights and ideals rest upon it. There is no instance in history when censorship and secrecy has advanced either democracy or public health.”
On February 10, Facebook removed Kennedy’s Instagram account because of his statements about Covid vaccination.
Kennedy, who is the chairman and chief legal counsel of Children’s Health Defense, has endlessly repeated that he is not “anti-vax”, but is pro vaccine safety.
In his statement in response to being deplatformed from Instagram, he said: “Every statement I put on Instagram was sourced from a government database, from peer-reviewed publications and from carefully confirmed news stories. None of my posts were false.
“Facebook, the pharmaceutical industry and its captive regulators use the term ‘vaccine misinformation’ as a euphemism for any factual assertion that departs from official pronouncements about vaccine health and safety, whether true or not.
“This kind of censorship is counterproductive if our objective is a safe and effective vaccine supply.”
Kennedy, whose Facebook account remains active, says the pharmaceutical industry has hastily created “risky new products” that are exempt from liability and long-term safety testing and have not received FDA approval.
Emergency use authorisation is a “mass population scientific experiment ”, Kennedy says.
Kennedy is one of 12 people whom the Center for Countering Digital Hate (CCDH) in the US has dubbed the ‘Disinformation Dozen’. The organisation says the 12 are responsible for about 70% of what they describe as “anti-vaccine content” that is shared on Facebook.
Facebook’s vice-president for content policy, Monika Bickert, wrote on August 18, that there had been a debate about whether the global problem of Covid-19 vaccine misinformation could be solved simply by removing 12 people from social media platforms.
“People who have advanced this narrative contend that these 12 people are responsible for 73% of online vaccine misinformation on Facebook,” she said. “There isn’t any evidence to support this claim.
“Moreover, focusing on such a small group of people distracts from the complex challenges we all face in addressing misinformation about COVID-19 vaccines.”
Bickert said Facebook had removed more than three dozen pages, groups and Facebook or Instagram accounts linked to the 12 people.
“We have also imposed penalties on nearly two dozen additional pages, groups or accounts linked to these 12 people, like moving their posts lower in News Feed so fewer people see them or not recommending them to others,” she added.
“We’ve applied penalties to some of their website domains as well so any posts including their website content are moved lower in News Feed. The remaining accounts associated with these individuals are not posting content that breaks our rules, have only posted a small amount of violating content, which we’ve removed, or are simply inactive.”
Bickert said that the 12 people dubbed the ‘Disinformation Dozen’ were only responsible for about 0.05% of all views of vaccine-related content on Facebook. “This includes all vaccine-related posts they’ve shared, whether true or false, as well as URLs associated with these people,” she added.
“The report upon which the faulty narrative is based analysed only a narrow set of 483 pieces of content over six weeks from only 30 groups, some of which are as small as 2,500 users.”
Bickert said there was no explanation for how the CCDH identified the content they describe as “anti-vax” or how they chose the thirty groups they included in their analysis.
“There is no justification for their claim that their data constitute a ‘representative sample’ of the content shared across our apps,” she added.
Bickert said that, since the beginning of the pandemic, across the entire Facebook platform, the company had removed more than 3,000 accounts, pages and groups “for repeatedly violating our rules against spreading Covid-19 and vaccine misinformation” and had removed more than 20 million pieces of content for breaking these rules.
Mercola, who is at the top of the CCDH’s list, is now removing all his online articles (more than 15,000 in number, written over 25 years). He says he will continue to publish new articles, but each one will be available for only 48 hours and will then be removed from his website.
“There was a recent NY Times article attacking me and it was one of the most widely distributed stories in the world,” Mercola said. “The article was loaded with false statements made about me and my organisation.”
Mercola say he and his staff have been harassed and threatened. He says CNN crews followed him from his home with two vehicles while he bicycled to the beach.
The White House press secretary, Jen Psaki, said the US administration had recommended to social media platforms that they form an enforcement strategy against those promoting false statements about the Covid-19 pandemic.
The president of Children’s Health Defense, Mary Holland, said: “Covid-19 vaccines use novel technology never before used in a human population. With that comes great unknown risks. The people of the world deserve to have this crucial information to protect their health and that of their children.”
SARS-CoV-2 variants present new challenges
On May 1, the WHO announced that it had assigned labels for key variants of SARS-CoV-2, using letters of the Greek alphabet. Labels are being assigned to variants that the WHO has designated Variants of Interest (VOIs) or Variants of Concern (VOCs).
The labels do not replace existing scientific names (e.g. those assigned by the global repository GISAID, Nextstrain, and PANGO), which convey important scientific information and will continue to be used in research, the WHO said.
“While they have their advantages, these scientific names can be difficult to say and recall, and are prone to misreporting. As a result, people often resort to calling variants by the places where they are detected, which is stigmatising and discriminatory,” the organisation added.
“To avoid this and to simplify public communications, WHO encourages national authorities, media outlets and others to adopt these new labels.”
The variant that is now causing worldwide concern is B.1.1.529 (Omicron), which has a large number of mutations. The forty countries in which it is reported to have been detected include South Africa, Botswana, Hong Kong, Israel, Brazil, India, Canada, the UK, the US, Sweden, the Netherlands, Austria, Italy, Belgium, the Czech Republic, France, Germany, Denmark, Portugal, Spain, France (Réunion), Australia. South Korea, and Nigeria.
Numerous countries have imposed new travel restrictions in reponse to the discovery of the new variant.
The European Commission said it would propose activating the “emergency brake” mechanism to stop air travel from the Southern African region.
The Technical Advisory Group on SARS-CoV-2 Virus Evolution (TAG-VE) was convened on November 26, 2021, to assess B.1.1.529.
The TAG-VE said that, “based on the evidence presented indicative of a detrimental change in Covid-19 epidemiology”, it had advised the WHO that B.1.1.529 should be designated as a VOC.
The EU’s European Centre for Disease Prevention and Control classified B.1.1.529 as a Variant of Interest.
The WHO cautioned countries against hastily imposing travel restrictions because of B.1.1.529, saying they should take a “risk-based and scientific approach” when implementing travel measures.