New information has been added to this article (updates at the end), but the statistics are as of the date of publication. Up-to-date statistics can be found here. At 18/4/2020 the number of global cases since the start of the pandemic was put at more than 2.5 million (active cases more than 1.5 million), and the global death toll was put at 154,331.
Billions of people around the world are now on lockdown as the spread of the novel coronavirus SARS-CoV-2, and the disease it causes, Covid-19, escalates.
More than half a million Covid-19 cases have been reported across 202 countries and territories, and the official death toll has been put at 30,883. However, the statistics are extremely unreliable. Many cases involving people with mild symptoms go unreported and, in a large percentage of cases, those who have died had underlying health problems. Some countries have efficient reporting systems, but the data from others may be a vast underestimation, or an overestimation.
The advent of the Covid-19 pandemic has brought out the best and the worst in people. Doctors, nurses, and others in the health services are risking their lives day in and day out to care for the sick and dying while survivalists, also known as preppers, stockpile supplies, including ammunition, to protect their goods and chattels.
As news programmes and social media bombard us with apocalyptic scenes, initially from Wuhan in China, and now from Lombardy in Italy, people have been fighting in the supermarkets over toilet rolls, and elbowing each other out of the way to grab a jar of Nutella.
The medical services in many countries are overwhelmed, with two few respirators for patients and insufficient protective clothing for staff. In Spain, patients in a critical condition who are aged over 65 are being taken off respirators and are being sedated and left to die.
The race is on, meanwhile, to find a vaccine against Covid-19. There are fears that a vaccine will be fast tracked and will cause more harm than good, and that vaccination against the novel coronavirus will, in some countries, be mandatory.
The witch hunt against those who question the wisdom of rushing through a vaccine with inadequate testing has begun, with certain mainstream publications leaping on the opportunity to go hammer and tongs against those they label as “anti-vaxxers”.
Such articles never mention vaccine injury or the legal cases that have ensued. In November last year, a court settlement was reached in Ireland in the case of a woman who developed narcolepsy after being vaccinated against swine flu (H1N1) during the 2009 pandemic.
Denmark has already brought in legislation that would enable forced vaccination.
There are at least 43 Covid-19 vaccines in development around the world, including in Australia, Hong Kong, the United States, and Britain.
A Phase 1 clinical trial for one vaccine began at the Kaiser Permanente Washington Health Research Institute in Seattle on March 16. Forty-five volunteers, aged between 18 and 55, were enrolled to take part. They will receive two shots about a month apart.
The vaccine is called mRNA-1273 and was developed by National Institute of Allergy and Infectious Diseases (NIAID) scientists and their collaborators at the biotechnology company Moderna, based in Cambridge, Massachusetts.
It uses messenger ribonucleic acid (RNA) and, the NIAID says, “directs the body’s cells to express a virus protein that it is hoped will elicit a robust immune response”.
In a recent Facebook Live discussion with S. Alice Mong from the Asia Society Hong Kong Centre, professor of epidemiology Marc Lipsitch said that one concern about every vaccine, but especially any vaccine that might be developed for Covid-19, is the possibility of “enhancement”, in which the vaccine creates an immune response that’s harmful to the control of the infection.
“That’s been seen in other coronavirus studies, so it’s a real concern,” said Lipsitch, who is director of the Center for Communicable Disease Dynamics at the Harvard T.H. Chan School of Public Health.
Lipsitch believes that SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2), will continue to spread widely. He predicts that, within the coming year, between 40 and 70 percent of the world’s population will be infected with SARS-CoV-2, but he considers it likely that many will have a mild form of Covid-19 or will be asymptomatic.
He told the writer for The Atlantic James Hamblin: “I think the likely outcome is that it will ultimately not be containable.”
More than 660,000 reported cases worldwide
The US has overtaken China and Italy and now reports more than 111,000 active cases of Covid-19.
Switzerland now has the most confirmed cases per million population, and is closely followed by Spain and Italy.
Iran has been extremely hard hit, with 2,517 people reported to have died after being infected with SARS-CoV-2. There are reported to be 21,212 active cases, and, in 3,206 of those cases, the patients are reported to be in a serious or critical condition.
However, when one calculates the number of cases per million population, Iran is in 14th place in the table of incidence, coming just after Estonia and Ireland. To date, Ireland has had 2,415 reported cases, 2,374 of which are active and 59 of which are patients in a serious or critical condition. The reported death toll in Ireland to date is 36.
In China, people are now starting to go out after two months of confinement, and factories are restarting production. However, on Thursday, the Chinese Ministry of Foreign Affairs announced that foreign nationals would be temporarily prohibited from entering the country. Imported Covid-19 cases are now the major concern in the country.
On Friday, mainland China reported its first locally transmitted Covid-19 case in three days and 54 new imported cases.
Some individuals, including diplomats and those providing necessary economic, scientific or technological services or emergency humanitarian support, are exempt from the travel restriction and can apply for a visa.
Thursday’s 55 new cases were down from 67 a day earlier, the National Health Commission said in a statement on Friday. The total tally of infections was put at 81,394 and the death toll at 3,295.
Globally, Thursday (March 26) was reported to be the single most deadly day since the pandemic began, with 2,532 new deaths in one day of people diagnosed with Covid-19.
There have, to date, been more than 660,000 reported cases globally and the number of current active cases is put at 490,859. Five percent of these patients are reported to be in a serious or critical condition.
Worldwide, more than 142,000 people are reported to have recovered.
Reporting in an article in the China CDC Weekly, published on February 17, Yanping Zhang et al. from The Novel Coronavirus Pneumonia Emergency Response Epidemiology Team said they had concluded that the overall chances of dying from Covid-19 were 2.3 percent.
The fatality rate rose to eight percent for patients in their 70s and 14.8 percent for those in their 80s. Out of the 44,672 patients with Covid-19 who were studied, the majority of those who died were aged 60 or older.
Among the 1,023 deaths, most were aged above 60 years of age and/or had had pre-existing, comorbid conditions such as hypertension, cardiovascular disease, and diabetes.
Italy’s National Institute of Health (Istituto Superiore di Sanità) examined the medical records of 2,003 patients who died and were diagnosed as being Covid-19 positive. In the resulting study, the researchers say that the average age of those who died was 79.5.
As of March 17, 17 patients who died and were Covid-19 positive were under the age of fifty. Five of them were aged under forty and all of these patients were males aged between 31 and 39 who had serious pre-existing pathologies, including cardiovascular or renal disease, diabetes, or obesity).
The researchers analysed the incidence of pre-existing illness in 355 of the patients and found that 48.5 percent of them had three or more pre-exisiting conditions.
Just three of the 355 patients had no previous pathology. More than 75 percent of them had high blood pressure, about 35 percent had diabetes, and 33 percent suffered from heart disease.
Three billion people locked down
One after the other, countries have closed their borders to non-citizens and have gone into varying degrees of lockdown.
More than three billion people around the world are now living under lockdown. Opinion continues to differ about whether lockdowns are the answer. There are expert scientists who say the lockdown measures are an overreaction. Others would go much further and, brushing aside claims that they are conspiracy theorists, say the restrictions are part of a global plan to corral populations and bring them to heel, with the aim of imposing a New World Order.
There are many who believe that draconian legislation being brought in because of SARS-CoV-2 will remain on statute books well after the virus disappears, if it ever does disappear.
Sweden has gone against the trend and has kept its borders, schools, shops, and restaurants open. The Swedish government has only banned events where there would be more than 500 participants. It recommends that people should stay seated in pubs and restaurants, and not mingle, and should think carefully about whether they need to take public transportation.
Swedes who become ill with Covid-19 can go back to work or school just two days after they feel well again.
Australia has closed its borders to foreigners, but it is only in the state of New South Wales that schools have been closed.
In an article for Britain’s Mail on Sunday, published on March 24, the controversial conservative journalist and author Peter Hitchens asks whether a full lockdown of Britain is the right answer in face of the coronavirus.
“The incessant coverage of health scares and supermarket panics has obscured the dire news coming each hour from the stock markets and the money exchanges,” Hitchens wrote.
“The wealth that should pay our pensions is shrivelling as share values fade and fall. The pound sterling has lost a huge part of its value. Governments all over the world are resorting to risky, frantic measures …,” Hitchens continued.
“Much of this has been made far worse by the general shutdown of the planet on the pretext of the coronavirus scare. However bad this virus is …, the feverish panic on the world’s trading floors is at least as bad.”
Hitchens pulls no punches, saying: “All the crudest weapons of despotism, the curfew, the presumption of guilt and the power of arbitrary arrest, are taking shape in the midst of what used to be a free country.
“Imagine, police officers forcing you to be screened for a disease, and locking you up for 48 hours if you object.”
Avoidable deaths are tragic, Hitchens writes, but each year there are already many deaths, especially among the old, from complications of flu leading to pneumonia.
“The Department of Health and Social Care (DHSC) tells me that the number of flu cases and deaths due to flu-related complications in England alone averages 17,000 a year. This varies greatly each winter, ranging from 1,692 deaths last season (2018/19) to 28,330 deaths in 2014/15,” Hitchens wrote.
‘The people of India have not committed a crime’
In India, police have been seen beating people who were not respecting confinement rules, and have forced some of them to do squats and press-ups.
The MP and author Shashi Tharoor has called on India’s Prime Minister, Narendra Modi, to stop police from using violent force.
“I have no doubt that most police personnel are doing a commendable job in these difficult times. However, those who brutalize citizens are bringing disrepute to the efforts of all others,” Tharoor wrote in a letter posted on Twitter on Friday.
He said “vigilantes” had also been spotted standing on corners and beating those who defied the lockdown orders. “We are better than this,” Tharoor said.
In a Facebook post, and addressing herself to Modi and the Home Minister, Amit Shah, Vrinda Grover, who is a lawyer, researcher, and human rights and women’s rights activist, said: “This lockdown is because of a health emergency. It’s not to aggregate more power in the hands of the state and give unbounded surveillance and policing powers to the state and police force.
“The people of India have not committed a crime. We are not being punished by being locked into our homes. We are not serving a sentence of house arrest for 21 days.”
What directions and instructions have the Union and state home ministers and police commissioners and state police across the country given to the police? Grover asked.
“The police are out there only to provide service and assistance to the people. The police cannot beat or humiliate anyone. Every cop who abuses power during the health emergency must be suspended.
“This lockdown is to enable all of us to live. And the cops are beating and torturing people. Every police vehicle should be giving a lift to the migrant workers walking miles to reach their homes. Police excesses are illegal and punishable.”
Grover points out that, “even in these dire times”, the government has refused to enhance the Internet speed in Kashmir from 2G to 4G.
“Health services are severely impacted in Kashmir, jeopardising the lives of the people of the Valley. At this crucial juncture we want information, services, answers from the government. Stop infantilising the citizenry.”
Grover urged Modi to give a daily update on health-related information. “We need information, answers, service and our money being used for the poor and vulnerable; for investing in strengthening public health facilities and improving access to health,” she said.
Amid the nationwide lockdown, thousands of migrant workers flocked yesterday (Saturday) to the Anand Vihar bus terminus in Delhi in the hope of being able to return to their villages.
The lockdown has rendered thousands of workers unemployed and they are obliged to run the risks of crowds and travel as they have too little money to survive in Delhi.
Thousands of people are under strict quarantine in northern India after a Sikh religious leader died of Covid-19.
The 70-year-old guru, Baldev Singh, ignored advice to self-quarantine after returning from a trip to Italy and Germany, and went preaching in more than a dozen villages in Punjab state. Baldev Singh joined a large gathering to celebrate the Sikh festival of Hola Mohalla shortly before he died.
The authorities in Maharashtra, which is the worst-hit state in India, have announced that about 11,000 convicted and under-trial detainees who are imprisoned for offences with a prescribed punishment of up to seven years are to be released on emergency parole or furlough to reduce overcrowding in prisons and reduce the risk of the spread of Covid-19.
The risk to prison inmates in such a pandemic is a major and global concern. The US attorney-general, William Barr, on Thursday recommended the release of at-risk inmates to home confinement for the remainder of their sentences.
Barr said federal authorities should prioritise the release of at-risk prisoners, including those with pre-existing medical conditions and the elderly.
The British government is among those also considering the release of some prisoners, including those who are pregnant.
Elderly left to die in Spain
In Spain, one doctor took to social media in tears to explain the difficult choices medical professionals are having to make when working in intensive care.
In the video, which can be seen on Twitter, he says that respirators are being removed from people aged over 65. The patients are then sedated and are left to die.
“There aren’t respirators for everyone and they want to give them to the youngest,” he said.
“We have a duty to this nation, to our elders. We can’t let them die in this worthless manner.”
The doctor replayed an audio message he has received, which describes the desperate situation in Madrid, where there are not enough doctors and nurses to deal with the crisis.
In the message a female doctor is heard saying: “A lot of patients have to be sedated and held by the hand since families can’t be by their side comforting them as they die.
“We’re told to put on a brave face, fill up with courage and go to work, knowing that you are going to have to let many people die.
“Cry at home, cry at night, but go to work the next morning.”
Testing and monitoring
In South Korea, the spread of Covid-19 is being combatted by mass testing and monitoring.
The South Korean Foreign Minister, Kang Kyung-wha, said in an interview on March 18 with the BBC’s Andrew Marr that the country had seen a stabilising trend for three days in a row, with the number of newly confirmed positive cases now smaller than the number of patients who were fully cured and discharged.
Kang Kyung-wha said nearly a quarter of a million people in South Korea had been tested to date.
“Testing is central because that leads to early detection, it minimises further spread, and it quickly treats those found with the virus,” Kang Kyung-wha said. “That’s the key behind our very low fatality rate as well.”
Kang Kyung-wha told Marr that the basic principle of the strategy in South Korea was openness and transparency, “fully keeping the public informed”.
There was a very good health care system that was “highly wired”, she said.
“After the Chinese authorities released the genetic sequence of the virus in mid-January, our health authorities quickly conferred with the research institutions here and shared that result with pharmaceutical companies who then produced the reagent and the equipment needed for the testing.”
South Korea has not locked down the country. It has closely monitored Covid-19 patients via a phone app. Inbound and outbound traffic to the country has also been closely vetted.
“The peak of new cases was in late-February, when we had over 900 new confirmed cases. That has now come down to 76 new cases as of today,” Kang Kyung-wha told Marr.
“We are definitely seeing a normalising trend and a reduction of new cases. But of course, we’re not complacent. This is not just about us … we are a country that is highly interdependent with the rest of the world. Our economy depends on this interdependency with the outside world so we want to keep the doors open with the other countries.”
Kang Kyung-wha told Marr that governments have to guard against panic. “I think governments have to be cool-headed about this and do what we do based on evidence and science.
“The declaration of the pandemic by the WHO risks turning the spread of the virus into a spread of fear and phobia. I can’t tell you how many incidents I get reports of: Asians not just Koreans being verbally abused, even physically attacked in other countries and governments have to take responsibility to stop this kind of incident because that is not helpful to generating the spirit of collaboration that we absolutely need to overcome this challenge together globally.”
In an article in the New Scientist, Michael Le Page explains how Covid-19 tests work.
Currently, most tests are based on looking for genetic sequences specific to SARS-CoV-2.
Rapid tests, such as the one that may roll out soon in Britain, Le Page explains, are usually based on detecting proteins rather than genetic sequences. These proteins can either be viral ones, called antigens, or the antibodies our bodies make to kill the virus. Antigen tests can directly detect the presence of the virus, but are less accurate than genetic tests.
The chair of global public health at the University of Edinburgh, Devi Sridhar, told POLITICO magazine: “It’s crazy not to be contact tracing. And the only way to do contact tracing is to know who’s actually infectious. And to do that you have to test.”
Sridhar said South Korea, China, and Singapore all conducted widespread contact tracing. In contrast, the UK was advising those with a high temperature or a cough to stay at home and not be tested.
Sridhar likened this to advice given to people who have the flu. “I think if we let this spread like it’s a seasonal infection, we will have a lot of deaths, a very overrun health service, and people affected in all ages,” she told POLITICO.
In the US, the government has acknowledged that the country does not have enough test kits.
Where did SARS-CoV-2 originate?
Social media is awash with theories about where SARS-CoV-2 might have originated. These range from the theory that the virus originated in wildlife to suggestions that it was released, either accidentally or on purpose, from the National Biosafety Laboratory in Wuhan, or that it came from the American biowarfare laboratory in Fort Detrick, Maryland.
There is even a story circulating – that would fit well into a spy novel or movie – about a gunfight in a market in Wuhan during which a vial containing a biochemical substance shattered when it was dropped by the person who had agreed to sell it to the Americans. The story got plenty of shares from netizens who didn’t realise that it was originally published on r/NoSleep, a section of Reddit dedicated to scary fiction stories.
Did SARS-CoV-2 originate in a seafood market in Wuhan? Did it come from bats? Did it originate in the United States? Was it released deliberately as a bioweapon?
There is also the theory that the expansion of the 5G network is either making people more vulnerable to respiratory illness, or even causing such illness. Then there is the issue of the highly toxic air pollution in Wuhan and northern Italy and many other locations.
The first reports of a novel pneumonia (Covid-19) in Wuhan were later in December 2019, but retrospective analyses have identified a patient with symptom onset on December 1.
Wu et al., writing in the Journal of the Chinese Medical Association, say that the first case on December 1 did not show history of Huanan seafood market exposure and the subsequent cases started on December 10.
“In the following days, a burst of cases was spreading from Wuhan to the whole Hubei province,” Wu et al. said.
The Huanan market was shut down on January 1, 2020, after the announcement of an epidemiologic alert by the local health authority on December 31, 2019.
The first exported case was into Thailand on January 13, 2020, Wu et al. say.
Xiaolu Tang et al. state in their paper in the National Science Review that coronaviruses are naturally hosted and evolutionarily shaped by bats.
“Indeed, it has been postulated that most of the coronaviruses in humans are derived from the bat reservoir. Unsurprisingly, several teams have recently confirmed the genetic similarity between SARS-CoV-2 and a bat betacoronavirus of the sub-genus Sarbecovirus,” the researchers said.
“The whole-genome sequence identity of the novel virus has 96.2% similarity to a bat SARS-related coronavirus (SARSr-CoV; RaTG13) collected in Yunnan province, China, but is not very similar to the genomes of SARS-CoV (about 79%) or MERS-CoV (about 50%).”
Charles Calisher et al. said that suggestions that the virus did not have a natural origin were “conspiracy theories”, which they condemned.
They said: “Scientists from multiple countries have published and analysed genomes of the causative agent, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and they overwhelmingly conclude that this coronavirus originated in wildlife, as have so many other emerging pathogens.
“This is further supported by a letter from the presidents of the US National Academies of Science, Engineering, and Medicine and by the scientific communities they represent.”
In an article published this month in Nature Medicine, Kristian G. Andersen et al. say it is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus.
“Our analyses clearly show that SARS-CoV-2 is not a laboratory construct or a purposefully manipulated virus,” the researchers said.
“It is improbable that SARS-CoV-2 emerged through laboratory manipulation of a related SARS-CoV-like coronavirus.”
If genetic manipulation had been performed, one of the several reverse-genetic systems available for betacoronaviruses would probably have been used, the researchers say.
The genetic data irrefutably show that SARS-CoV-2 is not derived from any previously used virus backbone, they add.
Andersen et al. propose two scenarios they say can plausibly explain the origin of SARS-CoV-2: natural selection in an animal host before zoonotic transfer, and natural selection in humans following zoonotic transfer.
The researchers say the high-affinity binding of the SARS-CoV-2 spike protein to human Angiotensin-converting enzyme 2 (ACE2) “is most likely the result of natural selection on a human or human-like ACE2 that permits another optimal binding solution to arise”.
They say that, as many early cases of Covid-19 were linked to the Huanan market in Wuhan, it is possible that an animal source was present at this location.
“Given the similarity of SARS-CoV-2 to bat SARS-CoV-like coronaviruses, it is likely that bats serve as reservoir hosts for its progenitor,” they stated.
They add that Malayan pangolins (Manis javanica) illegally imported into Guangdong province contain coronaviruses similar to SARS-CoV-2.
Although the RaTG13 bat virus remains the closest to SARS-CoV-2 across the genome, some pangolin coronaviruses exhibit strong similarity to SARS-CoV-2 in the receptor-binding domain (RBD), the researchers say. This includes all six key RBD residues, they wrote.
According to Andersen et al., this clearly shows that the SARS-CoV-2 spike protein optimised for binding to human-like ACE2 is the result of natural selection.
It is possible, the researchers say, that a progenitor of SARS-CoV-2 jumped into humans, acquiring the genomic features described in their analysis through adaptation during undetected human-to-human transmission.
“Once acquired, these adaptations would enable the pandemic to take off and produce a sufficiently large cluster of cases to trigger the surveillance system that detected it,” they wrote.
Andersen et al. say that if SARS-CoV-2 pre-adapted in another animal species, then there is the risk of future re-emergence events.
“In contrast, if the adaptive process occurred in humans, then even if repeated zoonotic transfers occur, they are unlikely to take off without the same series of mutations.”
The researchers say that, although the evidence shows that SARS-CoV-2 is not a purposefully manipulated virus, it is currently impossible to prove or disprove the other theories of its origin described in their article.
However, they say, since they observed all notable SARS-CoV-2 features in related coronaviruses in nature, they do not believe that any type of laboratory-based scenario is plausible.
Stuart Newman, who is a professor of cell biology and anatomy at New York Medical College, challenges the findings of Andersen et al. He is quoted by GMWatch as saying that a key argument used to deny that SARS-CoV-2 could be a genetically engineered strain that escaped from a laboratory actually points to the exact opposite. In other words, he is quoted as saying, it indicates that SARS-CoV-2 could well be genetically engineered and that it could have escaped from a lab.
In an email interview with GMWatch, Newman said: “The Nature Medicine paper points to variations in two sites of the spike protein of the new coronavirus that the authors claim must have arisen by natural selection in the wild.
“However, genetic engineering of one of these sites, the ACE2 receptor binding domain, has been proposed since 2005 in order to help generate vaccines against these viruses. It is puzzling that the authors of the Nature Medicine commentary did not cite this paper, which appeared in the prominent journal Science.”
Newman also told GMWatch: “The second site that Andersen et al. assert arose by natural means, a target of enzyme cleavage not usually found in this class of viruses, was in fact introduced by genetic engineering in a similar coronavirus in a paper they do cite. This was done to explore mechanisms of pathogenicity.”
Newman told GMWatch that he does not believe that changes were deliberately introduced to increase the pathogenicity of any single strain of SARS-CoV-2, but that the virus may have had genetically engineered components in its history before it was inadvertently introduced into the human population.
GMWatch also quoted the London-based molecular geneticist Michael Antoniou, who has also cast doubt on assertions that SARS-CoV-2 was not genetically engineered. He said that Andersen et al.’s reasoning was not conclusive because it was based largely on computer modelling, which, Antoniou says, is “not definitive but only predictive”.
Antoniou said that, while Andersen et al. may be correct in how they perceive SARS-CoV-2 to have arisen, the data they present “does not exclude the possibility that this new coronavirus variant could have been created through an in vitro, directed iterative evolutionary selection process”.
He added: “Using this method, a very large library of randomly mutagenised coronavirus spike proteins could be selected for strong binding to the ACE2 receptor and consequently high infectivity of human cells.
“The power of such directed evolution to select for optimal enzymatic and protein-protein interactions was acknowledged by the award of the Nobel Prize in Chemistry in 2018.”
GMWatch states: “Neither Dr Antoniou, nor Prof Newman, nor we ourselves make any suggestion that, in the event that genetic engineering was involved, the intention was to create a bioweapon. Such ‘enhanced infectivity’ research is carried out on viruses all over the world (and not just in China) to investigate their behaviour and to develop vaccines and other therapies, as well as for ‘biodefence’ purposes.
“But the question of whether genetic engineering did play a part in the emergence of SARS-CoV-2 must continue to be investigated so that humanity can place appropriate limits and safeguards on such research.”
While the idea that SARS-CoV-2 was released to further a mass vaccination agenda seems too far-fetched for most people to countenance there is much evidence that, whatever the origins of Covid-19, there could well be a plan to introduce global, mandatory vaccination, and this would merge with Bill Gates’ desire for “digital certificates”, contained in quantum-dot tattoos, to be introduced to identify who has been tested for Covid-19, who has recovered, and who has been vaccinated against it.
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.
In an article published in Cell on March 26, Zhang Yongzhen from the Public Health Clinical Centre and the School of Life Sciences at Fudan University, Shanghai, and Edward Holmes from the School of Life and Environmental Sciences and the School of Medical Sciences at the University of Sydney say that, as not all of the early Covid-19 cases were associated with the seafood and wildlife market in Wuhan, “it is possible that the emergence story is more complicated than first suspected”.
Genome sequences of “environmental samples” – likely surfaces – from the market have been obtained, and phylogenetic analysis reveals that they are very closely related to viruses sampled from the earliest Wuhan patients, Yongzhen and Holmes say.
“While this again suggests that the market played an important role in virus emergence, it is not clear whether the samples were derived from people who inadvertently deposited infectious material or from animals or animal matter present at that location.
“Unfortunately, the apparent lack of direct animal sampling in the market may mean that it will be difficult, perhaps even impossible, to accurately identify any animal reservoir at this location.”
Yongzhen and Holmes say that, while past experience with coronaviruses suggests that evolution in animal hosts, both reservoirs and intermediates, is needed to explain the emergence of SARS-CoV-2 in humans, “it cannot be excluded that the virus acquired some of its key mutations during a period of ‘cryptic’ spread in humans prior to its first detection in December 2019.
“Specifically, it is possible that the virus emerged earlier in human populations than envisaged (perhaps not even in Wuhan) but was not detected because asymptomatic infections, those with mild respiratory symptoms, and even sporadic cases of pneumonia were not visible to the standard systems used for surveillance and pathogen identification,” they said.
“During this period of cryptic transmission, the virus could have gradually acquired the key mutations … that enabled it to adapt fully to humans.”
Yongzhen and Holmes say it seems inevitable that SARS-CoV-2 will become the fifth endemic coronavirus in the human population.
“Coronaviruses clearly have the ability to cross species boundaries and adapt to new hosts, making it straightforward to predict that more will emerge in the future, although quite why coronaviruses possess this capacity in comparison to some other RNA viruses is unclear.”
The researchers say it is likely that the true number of cases of Covid-19 will be substantially greater than reported because very mild or asymptomatic infections will often be excluded from counts.
Yongzhen and Holmes say that, given the enormous diversity of viruses in wildlife and their ongoing evolution, arguably the simplest and most cost-effective way to reduce the risk of future outbreaks is to limit our exposure to animal pathogens as much as possible.
“While our intimate relationship with the animal world means we cannot build impregnable barriers, stronger action against the illegal wildlife trade and removing all mammalian (and perhaps avian) wildlife from wet markets will provide an important buffer,” they said.
Are there several strains of SARS-CoV-2?
There is much debate as to whether there are several strains of SARS-CoV-2, and whether some of them are more dangerous than others. Scientists in Iceland are reported to have found forty mutations. A pathologist in the US has identified five different strains.
One Thai doctor, Manoon Leechawengwongs, who is in charge of the intensive care unit at Bangkok’s Vichaiyut Hospital, and is a leading expert in respiratory illness, said that, prior to this month, Thailand was only affected by a milder strain of the virus.
However, he said, a more dangerous strain had been brought in from Italy.
The virus was introduced to a “super spreader” after a relative arrived back from Italy and fifty people were infected at a boxing event, Dr Leechawengwongs said. The number of confirmed cases in Thailand then rocketed.
According to Dr Leechawengwongs, the virus strain that came to Thailand from Italy has the power to kill far more people than Asian strains.
In a Facebook post Dr Leechawengwongs said that measures to contain the spread of Covid-19 in Thailand were not introduced in time.
He said that, at first, Thailand had between thirty and forty cases and one death and there was little change for many weeks. Thais who were infected at that time had been infected by a milder strain of SARS-CoV-2 that was prevalent in other parts of Asia such as Japan, South Korea, and Hong Kong, he said.
All this changed after the boxing event at the Lumpinee Stadium in Bangkok on March 6, Dr Leechawengwongs said.
Dr Leechawengwongs says that the SARS-CoV-2 strain that came to Thailand from Italy has a far higher mortality rate than the “Asian strains” because of its ability to cause severe respiratory disease.
There have now been 92,472 cases reported in Italy, 70,065 of which are reported to be active and the death toll is now put at 10,023. This is a mortality rate of 10.8 percent.
In South Korea, there have now been 9,583 confirmed cases and 152 deaths, which makes the reported death rate 1.58 percent.
It is argued that there is a very large elderly population in Italy, but Dr Leechawengwongs points out that Japan also has a big aging population, but has kept deaths to a far lower level. Dr Leechawengwongs argues that this is because the virus strain is different to the one spreading in Italy.
In a paper published in the National Science Review on March 3, Xiaolu Tang et al. state that they identified two different types of SARS-CoV-2: the L type and the S type.
Xiaolu Tang and his colleagues at Peking University in Beijing studied the viral genome taken from 103 coronavirus patients. In 72 cases they found the “L-type” and in 29 they found the S type.
They found the mutations at two locations on the genome.
In a separate analysis, the researchers found that the “S-type” was older and the L type was derived from it.
Xiaolu Tang et al. say that the L type is more prevalent and may be more aggressive than the “S-type”.
The researchers stated: “Whereas the L type was more prevalent in the early stages of the outbreak in Wuhan, the frequency of the L type decreased after early January 2020.
“Human intervention may have placed more severe selective pressure on the L type, which might be more aggressive and spread more quickly. On the other hand, the S type, which is evolutionarily older and less aggressive, might have increased in relative frequency due to relatively weaker selective pressure.”
The researchers say that it is currently unclear whether the L type evolved from the S type in humans or in intermediate hosts. It is also unclear, they say, whether the L type is more virulent than the S type.
Stay Elkjær, writing for the Danish publication Information quotes the director of the Icelandic biopharmaceutical company deCODE genetics, Kári Stefánsson, as saying: “We have found forty island-specific virus mutations. We found someone who had a mixture of viruses. They had viruses from before and after the mutation, and the only infections traceable to that person are the mutated virus.”
The Icelandic researchers’ study has yet to be formally reviewed by other scientists.
Information also quotes virologist Allan Randrup Thomsen from the Department of Immunology and Microbiology at the University of Copenhagen.
Thomsen is quoted as saying: “Coronavirus is known as a virus that can mutate reasonably violently. We have seen reports of variants from China already. In that way, it fits well with what one expects.”
He said it was interesting that the forty variants fell into three clusters that could be traced back to specific sources of infection.
He is quoted as saying he expects Covid-19 in the long run to evolve to be more contagious but less pathogenic.
Stefánsson told Information : “We have the genes from more than 400 infections. The interesting thing about that sequencing is that we can track where the virus came from. Some came from Austria. There is another type from people who were infected in Italy. And there is a third type of virus found in people infected in England. Seven people had attended a football match in England.”
The deCODE genetics researchers have found 48 cases of Covid-19 in which the person tested showed no symptoms of any kind.
In a research letter published in the medical journal JAMA on February 21, a group of Chinese scientists reported an apparent case of asymptomatic spread of the virus, from a patient with a normal chest CT scan.
They said that one previous study reported that an asymptomatic 10-year-old boy had Covid-19 infection, but he had abnormalities on his chest CT scan.
“If the findings in this report of presumed transmission by an asymptomatic carrier are replicated, the prevention of Covid-19 infection would prove challenging,” Yan Bai et al. stated.
Pathologist Sin Hang Lee, who is the director of Milford Molecular Diagnostics in Connecticut in the US, says four mutations of the virus have been identified in the US: two that were reported in California, one that was identified in Texas, and one that was found in Massachusetts.
“These four mutations were not reported from China at the time when I searched the GenBank databases,” Sin Hang Lee told Changing Times.
He told WTNH News 8 in Connecticut: “There are at least five circulating strains of the coronavirus. Some strains may be more virulent, causing more death than the others.
“False negatives have been reported all over the world – in China, in Europe, and in the United States – and the technology being used is not accurate enough.”
Sin Hang Lee has written to the WHO and White House Coronavirus Task Force representatives offering to retest borderline or questionable positive coronavirus samples.
The letter was sent to Margaret Harris and Eduardo Guerrero from the WHO and the director of the US’s National Institute of Allergy and Infectious Diseases, Anthony Fauci.
“It has been widely reported in the social media that the RT-qPCR test kits used to detect SARS-CoV-2 RNA in human specimens are generating many false positive results and are not sensitive enough to detect some real positive cases, especially during convalescence,” Sin Hang Lee wrote.
“The major technical flaw of RT-qPCR for molecular diagnosis is the limitation of the length of its DNA probe which is about 25 bases long or shorter. And hybridisation is not an accurate method to determine nucleotide sequences, the foundation of all nucleic acid-based diagnostics.”
Sin Hang Lee says there is a unique 398-base segment in the SARS-CoV-2 nucleocapsid (N) gene that not only has a 100 percent match with that in the virus detected in Wuhan, but that also contains four single-nucleotide mutations found in the viruses isolated from patients in California, Texas, and Massachusetts.
This segment of the gene can be targeted for accurate molecular diagnosis, he says.
Sin Hang Lee recommends a “nested RT-PCR” detection method, which is more sensitive than the testing method currently being used. Milford Molecular Diagnostics would then carry out Sanger DNA sequencing on the samples.
“DNA sequencing will guarantee no-false positive results if all positive reports are accompanied by two-directional sequencing electropherograms,” he said.
In its instructions for use of the RT-PCR test, the Centers for Disease Control and Prevention (CDC) in the US states: “The 2019-nCoV RNA is generally detectable in upper and lower respiratory specimens during infection. Positive results are indicative of active infection with 2019-nCoV but do not rule out bacterial infection or co-infection with other viruses. The agent detected may not be the definite cause of disease.”
Sin Hang Lee says the CDC’s recommended RT-qPCR test does not determine DNA sequence.
“It guesses by watching part of the shadow of a DNA sequence to determine the presence or absence of a gene, not measuring it directly. That is the basic flaw of RT-qPCR in science.”
PCR is not a diagnostic tool, Sin Hang Lee says, but Sanger sequencing is. “The GenBank tells you what it is by looking at the DNA sequence. The GenBank cannot tell you anything by looking at the curve or slope of a curve generated by RT-qPCR.
“If you submit the 398 letters to GenBank and ask the GenBank to search its databases, the GenBank’s answer is it is a segment of the N gene of SARS-CoV-2, beyond a reasonable doubt.”
The PCR technology was designed to generate a molecular mass of a target segment of DNA defined by a pair of primers in the test tube, Sin Hang Lee says.
“It is just like telling a copier to make billions of copies of an original paragraph in a book exponentially, using newly made copies as the templates to make other new copies. The copier does not decipher or read what it has copied.”
SARS-CoV-2 and SARS-CoV
SARS-CoV-2 shares between 80 and 90 percent of its genetic material with SARS-CoV, the virus that caused SARS (severe acute respiratory syndrome), which appeared in November 2002 in the Guangdong province of southern China.
An epidemic of SARS affected 26 countries and resulted in more than 8,000 cases in 2003.
Both viruses consist of a strip of RNA inside a spherical protein capsule that is covered in spikes.
The spikes lock on to receptors on the surface of cells lining the human lung – the same type of receptor in both cases – allowing the virus to break into the cell. Once inside, it hijacks the cell’s reproductive machinery to produce more copies of itself, before breaking out of the cell again and killing it in the process.
Writing in The Atlantic, Ed Yong explains that the spikes of SARS-CoV-2 recognise and stick to the ACE2 protein that is found on the surface of our cells.
“This is the first step to an infection,” Yong wrote. “The exact contours of SARS-CoV-2’s spikes allow it to stick far more strongly to ACE2 than SARS-classic did.”
Yong quotes Angela Rasmussen from Columbia University as saying “it’s likely that this is really crucial for person-to-person transmission”. In general terms, the tighter the bond, the less virus required to start an infection, Yong writes.
“Coronavirus spikes consist of two connected halves, and the spike activates when those halves are separated; only then can the virus enter a host cell,” Yong writes. “In SARS-classic, this separation happens with some difficulty. But in SARS-CoV-2, the bridge that connects the two halves can be easily cut by an enzyme called furin, which is made by human cells and – crucially – is found across many tissues.”
Most respiratory viruses tend to infect either the upper or lower airways,” Yong explains. “In general, an upper-respiratory infection spreads more easily, but tends to be milder, while a lower-respiratory infection is harder to transmit, but is more severe.
“SARS-CoV-2 seems to infect both upper and lower airways, perhaps because it can exploit the ubiquitous furin.”
Covid-19 patients have been treated with various cocktails of drugs, including a combination of the HIV antiretroviral drugs Ritonavir and Lopinavir, a combination that has been used successfully in several countries, including India.
However, Bin Cao et al. stated in an article published on March 18 in the New England Journal of Medicine that, after conducting a randomised trial, they concluded that “lopinavir–ritonavir treatment added to standard supportive care was not associated with clinical improvement or mortality in seriously ill patients with Covid-19 different from that associated with standard care alone”.
The researchers, who are from China, the United Kingdom and the United States, added, however, that, “in the modified intention-to-treat analysis, which excluded three patients with early death, the between-group difference in the median time to clinical improvement (median, 15 days vs. 16 days) was significant, albeit modest”.
Bin Cao et al. stated that the overall mortality in their trial (22.1 percent) was substantially higher than the 11 to 14.5 percent mortality reported in initial descriptive studies of hospitalised patients with Covid-19, which indicated that they had enrolled a severely ill population.
The trial involved 199 adult patients with laboratory-confirmed SARS-CoV-2 infections.
The anti-malarial drug hydroxychloroquine has been used in France, but there is controversy over its use.
The treatment is being actively proposed by professor Didier Raoult, the director of the Institut Hospitalo-Universitaire (IHU) Méditerranée Infection in Marseille.
On March 16, Raoult said that there had been positive results from clinical trials in which hydroxychloroquine, in the form of the drug Plaquenil, was given to patients. He said that, of the 24 patients with Covid-19 who were treated with Plaquenil, three-quarters of them were no longer carriers of the virus after six days. Ninety percent of the patients in the study who didn’t receive Plaquenil were still carriers after six days.
Raoult advocates using hydroxychloroquine in combination with azithromycin, an antibiotic used in the treatment of bacterial pneumonia, which has been used against the Zika virus.
The positive results in the treatment of Covid-19 are “even more spectacular” when hydroxychloroquine and azithromycin are used together, Raoult says.
Raoult casts aside the claims by other doctors that hydroxychloroquine is too dangerous to be used as a treatment for Covid-19. There are patients, he says, who have been taking it as a treatment for rheumatoid arthritis for thirty years. Ocular side effects never occur over a period of about ten days, which is the length of time such treatment would be needed in the case of Covid-19. They occur, he says, in the case of one percent of patients after five years’ treatment.
Hydroxychloroquine, Raoult says, can be contraindicated if a patient is taking the heart medication Cordarone, but this, he says, is derisory given the positive effects the drug can have.
Raoult says there are no major risks in the use of azithromycin, but, as a precaution, certain patients would need to undergo an electrocardiogram before they are given it.
He argues that using hydroxychloroquine, which is already well known, is safer than using new drugs whose toxicity has not yet been established.
Raoult has been prescribing chloroquine for 25 years and has been writing about it for thirty years and says it is crazy that, in France, the experience of Chinese doctors in the use of chloroquine was not properly taken on board earlier.
Elise Klement-Frutos, who is an infectious diseases specialist at the Pitié Salpêtrière hospital in Paris told the publication Marianne that care needed to be taken in the use of hydroxychloroquine and that people should not be taking it without proper medical advice.
On March 17, spokeswoman for the French government Sibeth Ndiaye said that France’s Health Minister, Olivier Véran, wanted the chloroquine clinical trial extended. She said testing would now be carried out with a team independent of professor Raoult.
The same day, the French pharmaceutical giant Sanofi said it could give the French government sufficient doses of Plaquenil, which is also used to treat lupus and rheumatoid arthritis, for 300,000 patients with Covid-19.
On March 23, Véran said chloroquine could be administered in France to patients suffering from the severest forms of the novel coronavirus.
He told reporters that France’s High Council for Public Health had recommended that the treatment should only be used in grave cases, when the patient was hospitalised, and only on the basis of a decision taken by doctors, and under strict surveillance.
The alert has been raised in several countries, including Nigeria, where people have been self-medicating with chloroquine and have suffered poisoning.
Two cases of chloroquine poisoning were reported after the US president Donald Trump touted hydroxychloroquine as a promising treatment for Covid-19. The two people were hospitalised in Lagos for chloroquine overdoses.
Health officials warned Nigerians not to self-medicate after demand for the drug surged in Lagos.
Oreoluwa Finnih, who is the senior health assistant to the governor of Lagos, said chloroquine was still in a testing phase in combination with other medication and had not yet been verified as a preventive treatment or a curative option.
In the United States, the governor of Nevada, Steve Sisolak, has banned the use of chloroquine and hydroxychloroquine to treat patients with Covid-19.
Sisolak said there was no consensus among experts or Nevada doctors that hydroxychloroquine or chloroquine were successful treatments for patients with Covid-19.
He said prescriptions for hydroxychloroquine or chloroquine should be limited to a thirty-day supply to ensure that it’s available for “legitimate medical purposes” and so that people didn’t stockpile the drugs.
Dr Michael J. Ackerman, who is a genetic cardiologist at the Mayo Clinic in Minnesota in the US says that hydroxychloroquine is known to cause drug-induced prolongation of the QTc of some people.
The QTc is an indicator of the health of the heart’s electrical recharging system. “Patients with a dangerously prolonged QTc are at increased risk for potentially life-threatening ventricular rhythm abnormalities that can culminate in sudden cardiac death, Ackerman said.
“Correctly identifying which patients are most susceptible to this unwanted, tragic side effect and knowing how to safely use these medications is important in neutralising this threat.”
Ackerman also says that hydroxychloroquine blocks one of the critical potassium channels that control the heart’s electrical recharging system.
“This interference increases the possibility that the heart’s rhythm could degenerate into dangerous erratic heart beats, resulting ultimately in sudden cardiac death,” he said.
India, where there are now 829 active confirmed Covid-19 cases, and there have been 20 deaths, has now banned all exports of hydroxychloroquine.
The Indian Council of Medical Research (ICMR) has warned against inordinate use of hydroxychloroquine and issued an advisory about using it as a preventive drug against Covid-19.
The ICMR’s head of epidemiology, Dr Raman Gangakhedkar, said the use of hydroxychloroquine as a preventive treatment for Covid-19 was “experimental” and should be restricted to asymptomatic healthcare workers involved in the care of suspected or confirmed cases of Covid-19 and asymptomatic household contacts of laboratory-confirmed cases.
Hydroxychloroquine should only be given when prescribed by a registered medical practitioner, Gangakhedkar said.
Large doses of vitamin C, administered intravenously, have been used to treat patients in China, and vitamin C has also been used as a treatment in New York.
Critically ill Covid-19 patients in Northwell Health facilities on Long Island are given a 1,500 milligram dose of vitamin C three to four times each day.
The vitamin C is reportedly being administered in addition to such medicines as hydroxychloroquine and azithromycin.
A study into the use of Vitamin C as a treatment for Covid-19 is being conducted at Wuhan University’s Zhongnan Hospital. It involves 140 patients.
Professor ZhiYong Peng notes in his description of the study that that vitamin C is an antioxidant that may help prevent cytokine-induced damage to the lungs.
ZhiYong Peng also states that vitamin C reduces inflammatory response, and prevents and shortens the duration of the common cold. Insufficient vitamin C is related to an increased risk and severity of influenza infections, he says.
The researchers are aiming to establish whether vitamin C has similar effects against the viral pneumonia associated with Covid-19.
The editor of the Chinese edition of the Orthomolecular Medicine News Service, Richard Cheng, says there are at least three clinical trials in China studying the effects of high-dose IV vitamin C for the treatment of Covid-19.
Dr Cheng says that preliminary results from the first high-dose IV vitamin C trial in China are reported to be promising.
In its “Shanghai Plan” (“Expert consensus on comprehensive treatment of coronavirus disease in Shanghai 2019), pre-published on March 1, the Shanghai Medical Association (SMA) endorses the use of high-dose intravenous vitamin C to treat Covid-19 patients and gives guidelines for its utilisation. The association recommends high-dose vitamin C even for minor cases.
The dose recommended by the SMA is 50 to 100 mg per kilogram of bodyweight per day. For severe and critically ill patients, up to 200 mg per kilogram of bodyweight per day is advised, injected intravenously. For the prevention and treatment of a cytokine storm (a severe immune overreaction), the SMA also recommends doses of unfractionated heparin.
The SMA says its consensus was reached by thirty experts who had been dealing with the Covid-19 epidemic in Shanghai. They based their decision on the research into more than three hundred cases and they drew on the experience of colleagues at home and abroad.
The association also recommends the use of hydroxychloroquine sulfate or chloroquine phosphate, or Abidol for oral administration, interferon nebulization, and inhalation. “Interferon κ is preferred, and interferon α, recommended by the national scheme, can also be applied,” they said.
“The combination of traditional Chinese and western medicine for the treatment of new coronavirus pneumonia can improve the synergistic effect.”
A medical team from Xi’an Jiaotong University’s Second Affiliated Hospital states that Covid-19 patients suffering from severe coronary pneumonia have recovered after being treated with high doses of vitamin C.
The medical team recommends that, for critically ill patients and those with severe neonatal pneumonia, vitamin C treatment should be initiated as soon as possible after admission to hospital.
The doctors say that high-dose vitamin C can not only improve antiviral levels, but can prevent and treat acute lung injury and acute respiratory distress.
They say the main cause of death of Covid-19 patients is cardiopulmonary failure caused by increased acute oxidative stress.
“When the virus causes increased oxidative stress in the body and increased capillary permeability, early application of large doses of vitamin C can have a strong antioxidant effect, reduce inflammatory responses, and improve endothelial function¹,” they said.
The team says the vitamin C treatment must be short-term (not exceeding one week) and should be combined with other drugs and treatment methods, and should not be given to certain patients, including those who are pregnant or lactating.
Convalescent plasma therapy
The Food and Drug Administration (FDA) in the US says it is possible that convalescent plasma that contains antibodies to SARS-CoV-2 might be effective against Covid-19.
The FDA stated on March 24: “Use of convalescent plasma has been studied in outbreaks of other respiratory infections, including the 2009-2010 H1N1 influenza virus pandemic, 2003 SARS-CoV-1 epidemic, and the 2012 MERS-CoV epidemic.
“Although promising, convalescent plasma has not been shown to be effective in every disease studied. It is therefore important to determine through clinical trials, before routinely administering convalescent plasma to patients with COVID-19, that it is safe and effective to do so.”
The FDA states that, given the public health emergency that the expanding Covid-19 outbreak presents, while clinical trials are being conducted, the FDA is facilitating access to Covid-19 convalescent plasma (immunoglobulins) for use in patients with serious or immediately life-threatening Covid-19 infections through the process of single patient emergency Investigational New Drug Applications.
This process allows the use of an investigational drug for the treatment of an individual patient by a licensed physician upon FDA authorisation. It does not include the use of Covid-19 convalescent plasma for the prevention of infection.
In an article published in The Lancet on February 27, Long Chen et al. said: “Evidence shows that convalescent plasma from patients who have recovered from viral infections can be used as a treatment without the occurrence of severe adverse events.
“Therefore, it might be worthwhile to test the safety and efficacy of convalescent plasma transfusion in SARS-CoV-2-infected patients.”
Long Chen et al. said: “Convalescent plasma has been used as a last resort to improve the survival rate of patients with SARS whose condition continued to deteriorate despite treatment with pulsed methylprednisolone.”
Several studies showed a shorter hospital stay and lower mortality in patients treated with convalescent plasma than those who were not treated with it.
In 2014, the use of convalescent plasma collected from patients who had recovered from Ebola was recommended by the WHO as an empirical treatment during outbreaks. A protocol for the use of convalescent plasma in the treatment of Middle East respiratory syndrome coronavirus was established in 2015.
During the swine flu (H1N1) pandemic, a prospective cohort study² by Hung et al. showed a significant reduction in the relative risk of mortality for patients treated with convalescent plasma. Additionally, in a subgroup analysis, viral load after convalescent plasma treatment was significantly lower on days 3, 5, and 7 after intensive care unit admission.
In an article published in The Journal of Clinical Investigation on March 13, Arturo Casadevall and Liise-anne Pirofski say that human convalescent serum is an option for the prevention and treatment of Covid-19 that could be rapidly available when there are sufficient numbers of people who have recovered and can donate immunoglobulin-containing serum.
Casadevall and Pirofski say that serum containing virus-neutralising antibodies could be administered to prevent infection in high-risk cases, such as vulnerable individuals with underlying medical conditions, health care providers, and individuals with exposure to confirmed cases of Covid-19.
“Additionally, convalescent serum could potentially be used in individuals with clinical disease to reduce symptoms and mortality. The efficacy of these approaches is not known, but historical experience suggests that convalescent sera may be more effective in preventing disease than in the treatment of established disease,” they stated.
“As we are in the midst of a worldwide pandemic, we recommend that institutions consider the emergency use of convalescent sera and begin preparations as soon as possible. Time is of the essence.”
Casadevall and Pirofski say that the available evidence from the use of convalescent sera in patients with SARS1 and MERS, and anecdotal evidence from its use in 245 patients with COVID-19 in China, suggest that it is safe.
“Nevertheless, in convalescent serum trials, caution and vigilance to identify any evidence of enhanced infection will be required,” they said.
Given the high mortality of Covid-19, particularly in elderly and vulnerable persons, the benefits of the use of convalescent sera in those at high risk for or with early disease outweigh the risks, Casadevall and Pirofski say.
“However, for all cases where convalescent serum administration is considered, a risk-benefit assessment must be conducted to assess individual variables,” they added.
Several mechanisms for antibody-dependent enhancement of infection (ADE) have been described in the case of coronaviruses and Casadevall and Pirofski say there is the theoretical concern that antibodies to one type of coronavirus could enhance infection to another viral strain.
“Since the proposed use of convalescent sera in the Covid-19 epidemic would rely on preparations with high titers of neutralising antibody against the same virus, SARS2-CoV-2, ADE may be unlikely,” they said.
An official with China’s National Health Commission, Guo Yanhong, said on February 28 that 91 patients had shown improvement after convalescent plasma therapy.
Guo said China had established expert task forces at provincial and national levels to analyse and improve the use of plasma therapy.
Homeopaths, meanwhile, have been studying cases and working to deduce which are the best remedies for their patients in face of the Covid-19 epidemic.
The Indian government’s Ministry of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (AYUSH), which promotes alternative medicine systems in the country, released a health advisory on January 29 that advocates the use of homeopathy and traditional Indian remedies to ward off infection by SARS-CoV-2. This includes a recommendation to take the homeopathic preparation Arsenicum album 30C.
Anil Khurana, who heads the Central Council for Research In Homeopathy (CCRH) of the Ministry of AYUSH, told Alakananda Dasgupta, writing for The Scientist, that Arsenicum album 30C has been in widespread use for more than 220 years and was found to be an effective prophylactic during the swine flu epidemic in India in 2009.
Also in India, a group of researchers, entrepreneurs, and administrators are working on a project called CASCAD (Collaborative AI Search for Covid-19 Antiviral Drug).
“It is important to explore if we can rapidly get to antiviral drugs by repurposing existing drugs, leveraging data and AI,” the group says.
“Drug repurposing involves figuring out whether a drug designed for one disease can be used effectively for another disease without going through the whole drug discovery cycle.”
Some repurposing is happening already, for instance with HIV drugs and Remdesivir, but the CASCAD group says more effort is needed, especially in a country like India, which is home to 1.3 billion people.
“A pandemic of this scale will certainly cripple our healthcare system if it extends to a full-blown cycle. One of the interesting approaches to shorten the cycle of response is to leverage AI driven drug repurposing.”
‘Masks protect others’
Correspondent in Hong Kong for the French newspaper Le Monde, Radio France and Radio France International, Florence de Changy, has written to the Director of Paris’s public assistance hospitals, Martin Hirsch, urging him to promote the wearing of a mask in the general public interest.
“In an epidemic, each person must see himself or herself as a potential carrier and be thinking of others,” she wrote.
De Changy said she was amazed to hear the French health authorities continuing to assert that masks were of little or no use.
“This seems to me to be very serious and dangerous. To the contrary, all French people should be encouraged to wear masks, not just those in the medical profession or the police.”
De Changy says that even if masks are poor protection for the wearer against Covid-19, they protect others.
“Several taxi drivers in Hong Kong who were wearing a mask were infected because their passengers were not wearing one.”
France has imposed restrictions that appear to be complicating and slowing down the importation and distribution of masks in France, De Changy says.
There could easily be a sufficient supply of masks in France she says. Their sale, she says, could be subsidised or they could be distributed for free.
“This would be a much smaller burden on the economy than the consequences of a drastic ‘Chinese-style’ confinement,” she wrote.
De Changy considers the extreme lockdown measures imposed in France to be neither viable nor sustainable as French people would not have the patience that Chinese people had in the face of governmental instructions.
“The terrible social and economic impact that this confinement will have risks being highly disproportionate to the results obtained in controlling the epidemic,” De Changy wrote.
People in Hong Kong had shown that, when the entire population wears a mask as a kind of “individual and mobile confinement”, it is possible to virtually halt the propagation of the virus, she added.
“Despite having a population density that is among the highest in the world (seven and a half million people, mostly living in miniscule spaces and very close to each other in daily life); despite people’s exchanges with China, and despite the geographic proximity with the first main sites of infection (until the closure of borders in mid-February), the death toll in Hongkong from Covid-19 is four,” De Changy wrote.
in Singapore, by contrast, the government urged the public not to wear masks so as to ensure adequate supplies for healthcare workers, and most people have not been wearing them.
There has meanwhile been much debate about whether home-made cloth masks are as protective as the thinner surgical masks. That debate continues.
The WHO says that people who are healthy only need to wear a mask if they are taking care of a person with suspected Covid-19 infection or are coughing or sneezing.
“Masks are effective only when used in combination with frequent hand-cleaning with alcohol-based hand rub or soap and water,” the WHO said.
“If you wear a mask, then you must know how to use it and dispose of it properly.”
A pandemic of panic?
A group of researchers, including Didier Raoult, published an article entitled “SARS-CoV2: fear versus data” in the International Journal of Antimicrobial Agents on March 19. They concluded that the problem of Covid-19 was “probably being overestimated”.
The researchers compared the incidence and mortality rates of four common coronaviruses with those of SARS-COV-2 in Organisation for Economic Co-operation and Development (OECD) countries.
In addition to coronaviruses, there are 16 endemic viruses in common circulation in developed countries, they explain.
In OECD countries, SARS-CoV-2 does not seem to be deadlier than other circulating viruses, Didier Raoult et al. say.
“It is concluded that the problem of SARS-CoV-2 is probably being overestimated, as 2.6 million people die of respiratory infections each year compared with less than 4,000 deaths for SARS-CoV-2 at the time of writing,” the researchers said.
There is little chance that the emergence of SARS-CoV-2 could significantly change the death toll from respiratory infections, Raoult et al. say
“Fear could have a larger impact than the virus itself; a case of suicide motivated by the fear of SARS-COV-2 has been reported in India.”
Coronaviruses that have rarely been tested systematically around the world may persist in the pharynx of asymptomatic people, representing a potential source of population immunity, Raoult et al. say
It should be noted, they add, that systematic studies of other coronaviruses, but not yet for SARS-CoV-2, have found that the percentage of asymptomatic carriers is equal to or even higher than the percentage of symptomatic patients.
“The same data for SARS-CoV-2 may soon be available, which will further reduce the relative risk associated with this specific pathology.”
Professor Peter C. Gøtzsche, who is a Danish physician, medical researcher, former leader of the Nordic Cochrane Center in Copenhagen, and director of the Institute for Scientific Freedom, also in Copenhagen, wrote a letter to the BMJ, which was published on March 8. He stated: “Almost everyone I talk to, lay people and colleagues … consider the coronavirus pandemic a pandemic of panic, more than anything else.”
Gøtzsche writes that case-fatality rates for respiratory virus infections are highly uncertain.
“Many mild infections pass unnoticed, and if an elderly frail patient with serious heart disease is pushed over the edge by an infection, was it then a virus death or a cardiac death?”
The estimate for the case-fatality rate for coronavirus infections is about 2 percent, Gøtzsche says.
“For the mild influenza pandemic in 2009, and the following years, the median case-fatality rate in the studies was around 1 percent for laboratory confirmed influenza.”
The WHO estimates that seasonal influenza may result in between 290,000 and 650,000 deaths each year that are due to respiratory diseases alone, Gøtzsche says. “About 4,000 have died so far from coronavirus.”
Is it evidence-based healthcare to close schools and universities, cancel flights and meetings, forbid travel, and isolate people wherever they happen to fall ill? Gøtzsche asks.
“No such draconian measures were applied during the 2009 influenza pandemic, and they obviously cannot be applied every winter, which is all year round, as it is always winter somewhere. We cannot close down the whole world permanently.
“The panic looks like an unfortunate overreaction. We don’t even know if the risk of dying if you get infected with coronavirus is higher than if you get influenza, or so many other virus infections, and most of those who die are old and suffer from comorbidity, just like for influenza.”
The harms include suicides that go up in times of unemployment, and when people’s businesses built up carefully over many years lie in ruins, they might kill themselves, Gøtzsche says.
In an article published in the New England Journal of Medicine on March 26, Anthony Fauci cites another article in the Journal in which Guan et al. report mortality of 1.4 percent among 1,099 patients with laboratory-confirmed Covid-19.
“These patients had a wide spectrum of disease severity. If one assumes that the number of asymptomatic or minimally symptomatic cases is several times as high as the number of reported cases, the case fatality rate may be considerably less than 1 percent,” Fauci wrote.
“This suggests that the overall clinical consequences of Covid-19 may ultimately be more akin to those of a severe seasonal influenza (which has a case fatality rate of approximately 0.1 percent) or a pandemic influenza (similar to those in 1957 and 1968) rather than a disease similar to SARS or MERS, which have had case fatality rates of 9 to 10 percent and 36 percent, respectively.”
In an article published in Science magazine on March 16, researchers Ruiyun Li et al. say that substantial undocumented infection facilitates the rapid dissemination of the novel coronavirus.
In their report on their study in China, the researchers said they estimated that 86 percent of all infections were undocumented prior to the travel restrictions imposed on January 23, 2020. By “undocumented” they mean the person was asymptomatic or had only very mild symptoms.
The researchers analysed the course of the epidemic in 375 Chinese cities between January 10 and 23.
They also analysed case data from foreign nationals who were evacuated from Wuhan, where the first cases were seen, and found a similar proportion of asymptomatic or very mild cases.
“Per person, the transmission rate of undocumented infections was 55 percent of documented infections … yet, due to their greater numbers, undocumented infections were the infection source for 79 percent of documented cases,” the researchers said.
“These findings explain the rapid geographic spread of SARS-CoV2 and indicate containment of this virus will be particularly challenging.”
Gaza, Syria, Bangladesh, and Yemen
SARS CoV-2 has brought serious stresses and strains for people throughout the world – separation from family and friends, being stuck in foreign countries with flights cancelled and visas expiring, elective surgery being postponed, and the worry of having to closing businesses and therefore losing income – and the global hotspots such as Italy and Spain are experiencing healthcare crises that are unparalleled in modern times (about 50 million people are estimated to have died during the Spanish flu pandemic).
There has, in numerous countries, been an increase in domestic violence. Because of the risk of contagion, people are dying alone without a relative or friend to hold their hand, and loved-ones are further traumatised as they are unable to put the deceased to rest as they would wish. There are no proper wakes, and a very limited presence at the graveside.
However, it is the areas of the world that are besieged, or ravaged by war, or already overwhelmed by a refugee crisis, where Covid-19 will be adding yet another level of devastation onto an already intolerable situation.
According to health officials in the besieged Gaza Strip, at least seven people have tested positive for Covid-19, bringing the total number of confirmed cases in the enclave to nine. Gaza’s nearly two million residents have been urged to stay at home.
Mohammed al-Tabatibi – the 79-year-old man who was one of the first two people to test positive for SARS-CoV-2 earlier this week – has told his grandson Shadi al-Tabatibi about the dire conditions where he is quarantined.
Speaking to Al Jazeera, Shadi al-Tabatibi said his grandfather had told him there was not enough equipment to deal with the disease and no appropriate medical care in the quarantine centre in the southern Gaza Strip.
“The people here are afraid, the streets are empty … it is like the days of the war in Gaza,” Shadi al-Tabatibi told Al Jazeera.
B’Tselem – The Israeli Information Center for Human Rights in the Occupied Territories – reports that, on Thursday (March 26), at about 7.30 a.m., officials from Israel’s Civil Administration in the West Bank arrived with a military jeep escort, a bulldozer, and two flatbed trucks with cranes at the Palestinian community of Khirbet Ibziq in the northern Jordan Valley.
“They confiscated poles and sheeting that were meant to form eight tents, two for a field clinic, and four for emergency housing for residents evacuated from their homes, and two as makeshift mosques,” B’Tselem said.
“The force also confiscated a tin shack in place for more than two years, as well as a power generator and sacks of sand and cement. Four pallets of cinder blocks intended for the tent floors were taken away and four others demolished.”
In an article in Al-Monitor headlined “Coronavirus in Syria: a catastrophe in the making”, Khaled al-Khateb writes that Syria’s first recorded Covid-19 infection was announced by the minister of health on March 23. The patient is a 20-year-old woman, who had been abroad.
There are now five recorded cases in the country.
On March 23, the government sterilised cities and villages and placed controls on commodity prices in Syrian markets, Al-Khateb wrote.
“It closed restaurants, cafes, parks, gyms, sports clubs, internet cafes and tourist facilities. It suspended conferences and launched sterilization and cleaning campaigns at the official departments, in public transportation, and in neighbourhoods and cities in the Syrian provinces. Authorities also banned the movement of travellers.
“Despite the government measures taken in record time, fears are increasing among the Syrian people. The prices of disinfectants, masks and cleaning materials soared as the supply of such materials became scarce due to the increasing demand. Also, the price of some necessary food commodities also increased in light of the rising demand.”
National Army media coordinator Yahya Mayo told Al-Monitor: “In light of the regime’s security and military grip, no international organisation or body can obtain real information about [cases of infections]. The opposition has obtained information from several Syrian regions and provinces confirming the existence of positive cases. The largest number of cases is recorded in Deir ez-Zor, Damascus, Aleppo and Latakia, which are the areas where Iranian militias are heavily deployed.”
The New Humanitarian (formerly IRIN News) reports that aid groups are warning of a potentially disastrous spread of Covid-19 to the rebel-held northwest.
“People in and around Idlib province – many of whom have fled for their lives in recent months – are left waiting, saddled with a new sense of dread.”
Aid agencies and NGOs have been planning for the pandemic’s arrival, disinfecting camps and trying to work out how medical care and containment might work in a part of the country where many hospitals and clinics have been bombed out of service during the long government offensive on rebels in the area, The New Humanitarian reports.
The first case of Covid-19 near to the Rohingya refugee camp at Cox’s Bazar in Bangladesh was reported on March 25.
Save the Children’s humanitarian advocacy manager, based in Cox’s Bazar, Athena Rayburn, said:”With reports of the first confirmed case in the local community in Cox’s Bazar, it’s just a matter of time until the virus reaches the vulnerable population living in cramped conditions in the largest refugee settlement on earth. Thousands of people could die.”
One million Rohingya refugees, half of whom are children, have been sheltering in sprawling camps in Cox’s Bazar since August 2017, when they were forced to flee their homes in the face of horrific violence.
“As global life grinds to a halt in a bid to contain the coronavirus, we must remember that for the Rohingya refugees in Bangladesh, their lives have already been in limbo for years; it is their status quo, and it will not end with the containment of coronavirus,” Rayburn said.
“We are now witnessing the impact that coronavirus is having in communities that can social distance, wash hands and have access to strong healthcare systems, yet this virus has still brought them to their knees.
“In the densely packed camps of Cox’s Bazar, options of social distancing or self-isolation are remote, with many refugees living in cramped conditions in makeshift shelters made of bamboo and tarpaulin. Even simple hygiene practices such as regular hand washing become complicated feats of logistical planning when access to clean water is severely limited.”
There are no reported cases of Covid-19 in Yemen, but the United Nations Development Programme (UNDP) says that “watching the invisible tsunami crashing through countries, and creating a global health crisis and economic catastrophe, we are preparing for landfall in Yemen, already one of the most fragile countries on earth”.
The protracted war in Yemen has decimated what was already a very weak health system. The UNDP says a Covid-19 outbreak would overwhelm it and the most vulnerable people would be hit the hardest.
“Fewer than 50 percent of Yemen’s hospitals and clinics are fully operational, and most lack qualified staff, medicine, and often even electricity,” the UNDP said.
On March 25, the UN Secretary-General, António Guterres, called for a ceasefire in Yemen to help avert a Covid-19 disaster. Today, the UN Special Envoy for Yemen, Martin Griffiths, urged the warring parties to act now. “Battlefields are dividing Yemen and making it harder to combat the possible outbreak of Covid-19,” he said. “Yemen needs its leaders to focus every minute of their time on averting and mitigating the potentially disastrous consequences of a Covid-19 outbreak.”
The UNDP said all the warring parties responded positively. “However, follow-through will be what saves potentially millions of lives. Everyone must put their differences aside, stop the fighting, and coordinate efforts to help mitigate Covid-19’s deadly spread.
“There must be local, national, and international coordinated public health policies to ensure Yemen’s swift and effective response.”
A threat to wildlife
In a joint statement, two groups from the International Union for Conservation of Nature (IUCN) – the Species Survival Commission (SSC) Wildlife Health Specialist Group and the Primate Specialist Group’s Section on Great Apes – said it was not yet known whether great apes are susceptible to SARS CoV-2.
“However, there is abundant scientific evidence that great apes are susceptible to infection with human respiratory pathogens,” the groups said.
“At this point, it is safest to assume that great apes are susceptible to SARS CoV-2 infection.”
The groups say it is strongly recommended that great ape visitations by humans are reduced to the minimum needed to ensure the primates’ safety and health monitoring.
For essential staff, great ape visitation rules need to be strictly enforced at all sites, the groups say. They specify maintaining a distance of at least seven meters from great apes at all times and strongly advise ten metres.
No person who is clinically ill, or who has been in contact with anybody ill in the preceding 14 days, should be allowed to visit great apes, the groups add.
The groups specify additional guidelines, including ensuring that all individuals coming close to great apes are wearing clean clothing and disinfected footwear prior to park entry. A surgical face mask must be worn by anyone coming within ten metres of great apes, they add.
In addition, they say, a 14-day quarantine should be imposed for all people arriving from outside the country who will come into more frequent and longer-term close proximity with wild great apes, e.g. veterinarians, researchers, and journalists.
“In the current situation and beyond the recommendations in the best practices, suspension of great ape tourism and reduction of field research should be considered,” the groups say.
“Deciding whether this additional measure should be implemented requires risk assessments integrating our rapidly evolving understanding of the situation based on new data, establishing mechanisms to offset loss of profit and employment from tourism, and bolstering public health in local human populations.”
Since March 17, all the centres run by the Borneo Orangutan Survival Foundation (BOSF) have been closed to the public. This includes the foundation’s information centre at the Nyaru Menteng Orangutan Rehabilitation Centre in Central Kalimantan and the Samboja Lodge at the Samboja Lestari Orangutan Rehabilitation Centre in East Kalimantan.
“At both of these locations we will no longer be accepting visitors or volunteers until the disease risk has been eliminated,” the BOSF said.
“Additionally, our release and research sites, including our camps in the Bukit Batikap Protection Forest, Bukit Baka Bukit National Park, Kehje Sewen Forest, and the Tuanan Research Area, will no longer be accepting new volunteers or researchers. We will be re-evaluating the situation and extending or ending the project closures on a monthly basis.”
Staff who continue to work with the orangutans have their temperature checked twice a day and are given leave if they run a fever or feel at all unwell. Staff who continue to work have increased the frequency of their hand washing, mask usage, and glove usage and all disposables are incinerated at the end of each day.
The BOSF offices that are not involved directly in animal care, such as the headquarters in Bogor and the Mawas Conservation Project Office in Central Kalimantan, are closed.
Coronavirus and the environment
The stories of dolphins swimming in the canals of Venice are fake news, but it is true that wildlife are benefitting from the current slowdown of global activity, and the spread of SARS CoV-2 has brought added weight to calls for an end to all wildlife trade. The pangolin, for instance, is one of the most trafficked mammals in the world.
In India, olive ridley sea turtles have come ashore for mass nesting at the six-kilometre-long Rushikulya beach in Odisha’s Ganjam district in recent days.
The New Indian Express reported that, since people have had to stay at home, more than 800,000 olive ridleys have come to Gahirmatha beach and the rookeries in Rushikulya.
On March 22, at about 2 a.m., 2,000 female olive ridleys started coming out of the sea to the beach, the Berhampur divisional forest officer, Amlan Nayak, told The Hindu.
Ankit Kumar from the Indian Forest Service said that recently people were treated to a rare visit by a white turtle.
On March 27, Kumar tweeted about wildlife claiming new habitats.
Environmentalists highlight the fact that global lockdowns have led to less pollution. As Covid-19 wreaks havoc and tragedy among populations, the Earth, is breathing more easily. How durable this environmental improvement will be remains to be seen.
- The endothelium is a thin membrane that lines the inside of the heart and blood vessels. Endothelial cells release substances that control vascular relaxation and contraction as well as enzymes that control blood clotting, immune function, and platelet adhesion.
- A prospective cohort study is a longitudinal cohort studythat follows, over time, a group of similar individuals (cohorts), who differ with respect to certain factors under study, to determine how these factors affect rates of a certain outcome.
Updated statistics available here.
Doctors say Covid-19 patients are suffering oxygen deprivation
Several doctors have attested that Covid-19 patients are presenting an atypical form of respiratory distress and should not be being treated according to standard protocols for the use of ventilators.
Cameron Kyle-Sidell, who is a critical care physician working in New York City, says the way ventilators are currently being used for Covid-19 patients could be doing more harm than good.
Kyle-Sidell has spoken out in a video posted on YouTube. He says he is seeing oxygen deprivation (something akin to high-altitude sickness), not acute respiratory distress syndrome (ARDS).
“In these nine days I have seen things I have never seen before. In treating these patients I have witnessed medical phenomena that just don’t make sense in the context of treating a disease that is supposed to be a viral pneumonia,” Kyle-Sidell said.
“Covid-19 lung disease, as far as I can see, is not a pneumonia and should not be treated as one.”
Kyle-Sidell says he has been surprised to see Covid-19 patients whom he thought he would be treating for ARDS who were talking in full sentences and not complaining of overt shortness of breath.
“I believe we are treating the wrong disease. And I fear that this misguided treatment will lead to a tremendous amount of harm to a great number of people in a very short time,” he said.
“It is as if tens of thousands of my fellow New Yorkers are on a plane at 30,000 feet and the cabin pressure is slowly being let out. These patients are slowly being starved of oxygen.
“I’ve seen patients depending on oxygen take off their oxygen and quickly progress to a state of anxiety and emotional distress and eventually get blue in the face. And while they look like patients absolutely on the brink of death, they do not look like patients dying of pneumonia.”
Kyle-Sidell is not saying that ventilators are not needed. “We absolutely need them. They are the only way at this time that we’re able to give a little more oxygen to patients who need it. But when we treat people with ARDS, we typically use ventilators to treat what’s called respiratory failure. That is, we use the ventilator to do the work that the patient’s muscles can no longer do because they’re too tired to do it. These patients’ muscles work fine.”
The method currently being used for Covid-19 patients aims to increase pressure on the patient’s lungs in order to open them up. This, Kyle-Sidell says, is doing more harm than good.
“The pressure that we are providing to lungs, we may be providing to lungs that cannot stand it, that cannot take it, and that the ARDS that we are seeing, that the whole world is seeing, may be nothing more than lung injury caused by the ventilator.”
The ventilators need to be used in a much safer way, Kyle-Sidell says.
In a letter to the editor published in the American Journal of Respiratory and Critical Care Medicine on March 30, Luciano Gattinoni et al. say that Covid-19 does not lead to typical ARDS.
Gattinoni, from the Department of Anesthesiology and Intensive Care Medicine at the Medical University of Göttingen in Germany, and his colleagues from hospitals in Milan said that patients with Covid-19 pneumonia have presented an atypical form of ARDS and that, if ventilators are used, they should be set on physiological findings rather than according to standard protocols.
The doctors said that, in northern Italy, an overwhelming number of patients with Covid-19 pneumonia and acute respiratory failure had been admitted to Intensive Care Units.
The clinical approach to these patients was the one typically applied to severe ARDS, namely high Positive End Expiratory Pressure (PEEP) and prone positioning.
Gattinoni and his colleagues say they have frequently observed severe hypoxemia and well-preserved lung mechanics in Covid-19 patients, and this has been confirmed by colleagues in other hospitals.
“Covid-19 pneumonia, despite falling in most of the circumstances under the Berlin definition of ARDS, is a specific disease, whose distinctive features are severe hypoxemia often associated with near normal respiratory system compliance,” the doctors stated in an article for the medical journal Mayo Clinic Proceedings.
Gattinoni and his colleagues said this was the case for more than half of the 150 patients they had assessed, and was further confirmed by several colleagues in northern Italy.
“This remarkable combination is almost never seen in severe ARDS,” the doctors said.
Gattinoni and his colleagues suggest the lowest possible PEEP and gentle ventilation.
Scientists at deCODE genetics and their colleagues from Iceland’s Directorate of Health and the National University Hospital say 291 mutations of SARS-Cov-2 have been found in the country that have not been identified elsewhere.
The researchers published an article in the New England Journal of Medicine about the early spread of SARS-Cov-2 in the country.
They say that analysis of sequence data reveals that the haplotypes of the virus detected in the early targeted testing were almost entirely of the A2 clade originating in Austria and Italy and entering Iceland with people returning from skiing holidays. (Haplotypes are a set of genetic determinants located on a single chromosome.)
“By contrast, the cases identified in the more recent targeted testing and in deCODE’s population screening show that various haplotypes of the A1 clade prevalent in countries such as the UK had become more common, and that there is now a wide and growing variety of haplotypes present in the population,” the researchers said.
“This suggests that the virus entered Iceland from many countries, including those that were then deemed low-risk.”
Researchers from Germany and England have meanwhile identified three main variants of the virus, distinguished by amino acid changes, which they have named A, B, and C.
In an article published in the Proceedings of the National Academy of Sciences of the United States of America, Peter Forster et al. say that type A is the “ancestral type according to the bat outgroup coronavirus”.
They added: “The A and C types are found in significant proportions outside East Asia, that is, in Europeans and Americans. In contrast, the B type is the most common type in East Asia, and its ancestral genome appears not to have spread outside East Asia without first mutating into derived B types, pointing to founder effects or immunological or environmental resistance against this type outside Asia.”
Forster says that the Wuhan B-type virus could be immunologically or environmentally adapted to a large section of the East Asian population.
“It may need to mutate to overcome resistance outside East Asia. We seem to see a slower mutation rate in East Asia than elsewhere, in this initial phase,” he said.
He added: “The viral network we have detailed is a snapshot of the early stages of an epidemic, before the evolutionary paths of Covid-19 become obscured by vast numbers of mutations. It’s like catching an incipient supernova in the act.”
The research team has extended its analysis to 1,001 viral genomes. While yet to be peer-reviewed, Forster says the latest work suggests that the first infection and spread among humans of Covid-19 occurred between mid-September and early December last year.
Forster et al. say that, outside of East Asia, 10 B-types were found in viral genomes from the United States and Canada, one in Mexico, four in France, two in Germany, and one each in Italy and Australia.
While the ancestral B type is monopolised (26/26 genomes) by East Asians, they say, every single (19/19) B-type genome outside of Asia has evolved mutations.
Type C is the major European type, the researchers say and is represented in France, Italy, Sweden, and England, and in California and Brazil. It is absent in the mainland Chinese sample, but evident in Singapore and also found in Hong Kong, Taiwan, and South Korea.
The case of the single Mexican viral genome in the network is a documented infection diagnosed on February 28, 2020, in a Mexican traveller to Italy, Forster et al. say.
“Not only does the network confirm the Italian origin of the Mexican virus,” they said, “but it also implies that this Italian virus derives from the first documented German infection on 27 January 2020 in an employee working for the Webasto company in Munich, who, in turn, had contracted the infection from a Chinese colleague in Shanghai who had received a visit by her parents from Wuhan.
“This viral journey from Wuhan to Mexico, lasting a month, is documented by 10 mutations in the phylogenetic¹ network.”
In separate research, two Chinese researchers have made discoveries that fit in with observations that Covid-19 patients are suffering from oxygen deprivation.
In an article published in the open-access, preprint archive ChemRxiv, researchers Liu Wenzhong and Li Hualan say that, in cases of Covid-19, it appears not to be the patients’ lungs that are attacked by SARS-CoV-2 in the first instance. The researchers say that virus proteins attack a component of hemaglobin (the heme group), thus interfering with the transport of oxygen.
“We believe that the damage of the virus to the human body is systemic, not confined to the respiratory system,” they said.
The researchers’ findings fit in with the observations of Cameron Kyle-Sidell, Luciano Gattinoni, and others that Covid-19 patients are suffering from oxygen deprivation (something akin to high-altitude sickness), not acute respiratory distress syndrome (ARDS).
Liu Wenzhong and Li Hualan said their study indicated that certain proteins could coordinate an attack on the heme² on the 1-beta chain of hemoglobin.
“The attack will cause less and less hemoglobin that can carry oxygen and carbon dioxide,” the researchers said.
The lung cells become poisoned and inflammatory because of the inability to exchange carbon dioxide and oxygen frequently and this eventually results in ground-glass-like lung images, they add.
Liu Wenzhong and Li Hualan say that, when hemoglobin is decreasing and the heme is increasing, the body accumulates too many harmful iron ions, which causes inflammation. Cells react to the stress caused by inflammation by producing large amounts of serum ferritin to bind free iron ions to reduce the damage.
1. Phylogenetics is the study of the evolutionary relatedness among groups of organisms.
2. One of the most important functions of blood is to carry O2 to all parts of the body via the hemoglobin protein. Transportation of oxygen is accomplished by the heme group. Heme groups are embedded in the hemoglobin protein. A heme group is a metal complex. Iron is the central metal atom and it can bind or release molecular oxygen.
Researchers in China have detected 33 mutations of SARS-CoV-2, including 19 that were previously undiscovered.
Lanjuan Li et al. found that some of these mutations could lead to functional changes in the virus’s spike protein, which SARS-CoV-2 uses to attach itself to human cells.
“We provide direct evidence that the SARS-CoV-2 has acquired mutations capable of substantially changing its pathogenicity,” Li and her collaborators wrote in a paper that has not been peer reviewed and was published on the preprint server medRxiv on April 19.
The researchers found that the most aggressive strains of Sars-CoV-2 could generate 270 times as much viral load as the least potent type.
The mutations that had the highest viral loads had also been found in most patients across Europe, according to Li and her colleagues. Those strains with lower viral loads were the predominant ones found in parts of the United States.
Li et al. analysed the SARS-CoV-2 strains isolated from 11 randomly chosen Covid-19 patients from Hangzhou in the eastern province of Zhejiang. They examined how the virus acted on cells. Li and her team used a sophisticated method known as ultra-deep sequencing.
“A diverse collection of mutations was identified in the 11 viral isolates, including two sets of founding mutations for two major clusters of viruses currently infecting the world population,” Li et al. wrote.
The researchers found that 19 of the identified mutations were novel. This was despite the relatively early sampling dates and indicated that “the true diversity of the viral strains is still largely underappreciated”, they said.
All of the 11 viral isolates had at least one mutation.
The researchers found three consecutive changes – known as tri-nucleotide mutations – in one patient. This is a rare occurrence. The patient remained positive for “an astounding period of 45 days,” Li et al. said. “Investigating the functional impact of this tri-nucleotide mutation would be highly interesting.”
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