CORONAVIRUS – Virus born under X. A year ago, to the day, the World Health Organization officially declared the scourge of Sars-Cov 2 a pandemic. Since then, nearly 2.6 million people have died across the world as a result of this disease, without knowing how and especially when exactly it was really born.
Last month, an investigation conducted by WHO experts in collaboration with Beijing failed to concretely elucidate the origins of Covid-19. The final report, the results of which are believed to be tainted by pressure from China, is due the week of March 15. For the moment, none of the preliminary elements communicated seem to provide answers on when and how the Covid-19 appeared. However, over the past year, several tools have made it possible to better understand the evolution of the virus and how it circulated. This includes studying the mutations of the virus but also identifying any traces it may have left behind.
Establish the family tree of the virus
The first method consists in particular of looking at the genealogical tree of the virus. To date, all the variations identified in the four corners of the globe, such as the English or the South African, have as a common ancestor the strain detected in Wuhan in December 2019. To dissect the genome, scientists thus resort to phylogenesis . “We can make an analogy with the evolution between old French and current French. It’s the same with the genome, we look at how it was written before, how it is written now and we deduce the modifications ”, explains Jacqueline Marvel, research director at the CNRS and immunologist at the international center for research in infectious diseases. Lyon, contacted by The HuffPost.
A bit like a tree whose trunk you cut to observe the circular streaks and thus assess its age, with one difference: “a virus does not mutate constantly. There are two types of mutations. First of all the neutrals. They appear randomly and provide no advantage or disadvantage. Then there are the mutations which precisely cause an advantage or a disadvantage, and therefore will spread in the population at a different speed ”, details in HuffPost Franck Perez, director of the cell biology and cancer unit at the Institut Curie and director of research at the CNRS.
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“As long as we do not find a strain of Sars-Cov2 elsewhere and earlier than the first traces around Wuhan, we have no reason to believe that the origin is elsewhere”, abounds Franck Perez.
There remains the question of when this “common ancestor” was born. Even though the first patient with the new coronavirus was identified in China on December 8, 2019, it cannot be said exactly when this strain appeared. The most probable hypothesis currently remains that of transmission via bats. “There is 96% homology between Sars-Cov2 and coronaviruses detected in bats. It’s very close, but unfortunately this difference of 4% remains significant and does not allow us to make the leap between animals and humans ”, explains Jacqueline Marvel.
Take the samples out of the cupboard
To fill “this black hole”, point the two scientists, one of the keys is to study older samples. They are the ones who could possibly identify the route taken by the Wuhan strain, even perhaps before December 8, the day when the first patient with symptoms of the new coronavirus was identified in this metropolis of Hubei province.
In this context, there are two main avenues possible: finding traces of virus directly via a PCR test and sequencing them, or finding traces of antibodies via serology. Each has its advantages and disadvantages “Analysis of viral genomes remains the most reliable method. The patient files should be taken back with lung x-rays that could have suggested a Covid-19 infection and blood samples should be found. But the problem with PCR is that the viral load in the blood can be very low and therefore more difficult to sequence ”, explains Franck Perez.
The advantage of serological analysis points the researcher: the antibodies remain for a long time in the plasma stored in the freezers of biological resource centers. However, the method is not perfect and presents the risk of encountering cases of cross-reactivity. In concrete terms, some people can develop an immune response to a cold – which is also caused by a virus from the coronavirus family – which will be similar to that developed by people infected with Sars-Cov2. “In one year, we managed to refine the tests, but doubts may remain,” says Jacqueline Marvel.
A virus present in spring 2019 in Europe?
Over the past year, numerous studies have attempted to look for traces of Covid-19 in samples dating from before December 2019. Among those that have attracted the most comments is a study by the University of Barcelona dating from l appearance of Covid-19 in the city’s wastewater from March 2019.
Published only on Medrxiv, this analysis was not “peer reviewed”, or “peer reviewed”. “It should therefore be taken with precaution. These researchers found via PCR tests only traces of the genome. In the end, out of all the samples they tested, only one is positive, ”warns Jacqueline Marvel, who rather refers to the case of cross-contamination between samples. “When you do a PCR test, you end up with an extremely concentrated product. It is therefore very easy, simply with the ambient air, to have contamination. In laboratories, when we carry out a PCR, we go so far as to change rooms to add our different products. We put on UV lights to destroy any nucleic acids that might be left. But contaminations can happen ”.
Moreover, emphasizes Franck Perez, the storage conditions in wastewater being very poor, they make precise sequencing of the virus almost impossible.
The trail of autumn becomes clearer
If the scientific community gives little reliability to these Spanish results, others raise new questions. This is particularly the case for the work of French researchers published in early February in the journal European Journal of Epidemiology. They analyzed 9,144 blood samples from a cohort of 200,000 people to find antibodies linked to the coronavirus. Ten samples taken between November or December were found to be positive. However, according to the Ministry of Health, the first patients listed on French territory were taken care of on January 24, 2020.
Another study, this time in Italy, tends to trace the first cases of Covid-19 to the fall of 2019. A study by the National Cancer Institute (INT) in Milan showed last November that at least four people, volunteers within the framework of a large study on lung cancer, presented as early as October antibodies to Sars-Cov2. Which would suggest an infection as early as September.
For one of the co-authors of the study, Giovanni Apolone, director of the INT, who spoke to Reuters, “This means that the new coronavirus was able to circulate within the population with a low case fatality rate, not because it was disappearing, but rather to reappear better”.
These conclusions slightly upset the conclusions of a report dating from May 2020 by Imperial College in collaboration with the WHO and which thus made the “common ancestor” of the virus go back to December 5 (with a margin of uncertainty between November 6 and December 13). “It is normal for a new virus to circulate without being detected for weeks before being discovered”, then stressed to AFP, the epidemiologist of Imperial College, Dr Erik Volz.
The pathogen in question
Without speaking of intense low-noise traffic, Franck Perez like Jacqueline Marvel also concede that it is very possible that isolated cases of the new coronavirus circulated in Europe before December. More and more, the cursors are heading towards the month of November.
“I have doubts about a possible very old origin of this virus because it has nevertheless demonstrated an important capacity to create clusters. It would have been seen, especially in nursing homes. Even wearing masks and applying barrier gestures, it continued to spread ”, estimates Franck Perez.
“We know that it is a virus sensitive to climatic conditions and hydrometry, perhaps these are parameters that have prevented a large infection before. It is not impossible either that less pathogenic sources have circulated weakly among us before ”, he specifies, also referring to a study of May 2020 published in Nature by Australian and British researchers among others.
This then evoked the idea that the pathogenic mutation that led to the current pandemic would have occurred after a first zoonotic contamination in humans. Concretely, an animal would have transmitted Sars-Cov2 to a person without the virus then being transmissible between humans or being able to replicate massively. It is only after this first transmission that the virus would have mutated to become pathogenic.
For Jacqueline Marvel, it is in any case the argument of seasonality that should push to deepen research on the Wuhan side. “We cannot say that the epidemic started a year before because it would be surprising if the virus remained latent for so long. On the other hand, there is a chance that patient zero in France emerged in the fall and went unnoticed, ”explains the immunologist. In Beijing, it was first whistleblowers who sounded the alarm before the public authorities, even if “in the meantime, exchanges between China and the rest of the world have continued”.
Back to Wuhan
However, as acknowledged in an interview with ScienceMag Dr Peter Ben Embarek, who led the WHO team of scientists sent to China, everything points to the virus circulating in the Wuhan region before the first officially detected cases.
“It is now clear that during the second half of December [2019], the virus has circulated widely in Wuhan. The contribution of the market at that time was no longer so important because the virus was also circulating elsewhere in the city (…) But everything indicates an introduction into the human population of this region between October and the beginning of December 2019 – probably at the end of November, shortly before the first cases were discovered. But the route of introduction remains a mystery, ”he explained, recalling that Wuhan is also an important hub in terms of transport and international trade.
Before the WHO mission began, Chinese scientists had identified 72,000 of these cases between October and December, some of which could be Covid-19 cases.
After applying a series of criteria, they ended up establishing a list of only 92 cases, according to them, worthy of examination to see if they could have been cases of contamination by the coronavirus. 67 of them gave rise to serological tests which were all negative for Covid. However, regrets Peter Ben Embarek, he could not obtain an explanation on the various criteria which had made it possible to go down from 72,000 to 92 cases.
It is therefore logical that at the end of its visit, the WHO encouraged Beijing to do new and more extensive analyzes on blood samples dating from before December 2019.
See also on The HuffPost: Covid-19: Why monoclonal antibodies will not replace vaccines
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