At the origins of Covid, the Wuhan market? Why it’s not so simple

What happened between October and December 2019 in the Chinese megalopolis of Wuhan, where the first documented cases of Covid-19 were recorded? For almost three years, the question has been agitating the scientific community. What do we know about the origins of this viral disease which has claimed more than 6 million lives worldwide? Very few things, in the end. Last June, a team of renowned scientists (composed of experts from the United States, China and 25 other countries) convened by the World Health Organization (WHO) delivered its conclusions. They could fit in one sentence: all options are on the table, including a lab accident. Tuesday, July 26, two studies published in the prestigious journal Science want to be more affirmative: the pandemic would have started on the seafood market of Huanan, in Wuhan, thus pointing to an animal origin of the virus. But there again, the conditional remains rigorous.

The first study is a geographical analysis showing that the first cases detected in December 2019 were concentrated around the market, unlike those recorded in the following months, which coincided with high-density neighborhoods, showing the spread of the virus. In addition, among the cases recorded, a large number of people were probably infected because of their proximity to this place, especially those who lived nearby. The researchers also analyzed samples taken from the market in January 2020, for example from a cage or trolleys. Their analyzes show that the samples positive for Sars-CoV-2 were concentrated in the south-west of the market, precisely where live animals were sold (including raccoon dogs, a species of badger, foxes, etc.).

The second study is a genomic analysis of the virus from the first cases. She concludes that two lineages of the virus, A and B, existed before February 2020. And that these two lineages likely resulted from two separate human transmission events, both at the Wuhan market. Previous studies had suggested that lineage B had evolved from lineage A. Conclusion: it is very unlikely that the virus circulated widely in humans before November 2019.

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The quest for the intermediary animal

Do these two studies close questions about the origins of Sars-CoV-2? The answer is no. But they refocus the debates around the Wuhan market, which until then was considered more as a place of superpropagation of a virus which had already turned elsewhere. In addition, they put aside the track of a laboratory accident linked, among other things, to the fog which still surrounds the work of the Wuhan Institute of Virology (WIV) today. Finally, they put the thesis of a zoonosis back at the center of the game. One of the authors of these studies himself, Michael Worobey, a virologist at the University of Arizona, had signed a letter in 2021 calling for serious consideration of the hypothesis of a leak from a scientific complex in Wuhan. But the data analyzed since “has made me evolve, to the point that today I also think that it is simply not plausible that the virus was introduced in any other way than through trade. of animals at the Wuhan market,” he said at a press conference. Kristian Andersen of the Scripps Research Institute, also a co-author of the studies, said: “Have we disproved the lab leak theory? No. Can we ever? No . But I think it’s important to understand that there are possible scenarios, and probable ones.”

In reality, these studies take us back three years, when the market was considered the place of origin of the pandemic. “It is obvious that this place played a role, but which one? Is it the initial element or a superpropagator?, tempers Etienne Decroly, virologist at the CNRS at the University of Aix-Marseille. If it is the initial element the origin of the pandemic, then it involves finding the progenitor virus [NDLR : l’ancêtre commun du Sars-CoV-2] in an animal sold on the market. However, to my knowledge, all the sequencing work carried out in this market has not made it possible to flush it out”. Another difficulty: to differentiate a superpropagation element from an original element, it is necessary in particular to analyze the sequences from the beginning of the outbreak.” Unfortunately, we know there are some missing footage. So these two studies, as rigorous as they are, were done in the context of currently available data. However, these are incomplete”, continues the scientist. Especially since, very quickly and due to the health emergency, the Chinese authorities emptied and sterilized the market, thus making the search for a possible intermediate animal very difficult. .

To focus too much on the Wuhan market, we would almost forget the work to identify a possible progenitor virus. In September 2021, the closest cousin of Sars-CoV-2 was identified in a horseshoe bat in Laos. Called BANAL-5, it is 96.85% identical to Sars-CoV-2. Until then, the coronavirus closest to it was a strain called RaTG13, whose complete genetic sequence has a 96.2% identity with the virus responsible for Covid-19. It was isolated in 2013 in a copper mine in Yunnan, southwest China, by researchers from the Wuhan Institute of Virology (WIV). “We now need to fill the missing links between these viruses present in bats, particularly in southwestern China, and the first documented cases of infections in Wuhan at the end of 2019. It is also important to understand how the virus has acquired an effective capacity for propagation in humans, which usually involves sporadic infections detectable before the start of the pandemic”, specifies Etienne Decroly.

“Science on Quicksand”

Another discovery from the Institut Pasteur in Laos showed that BANAL-5 has an RBD (Receptor Binding Domain) capable of binding to the ACE2 receptor of human cells with high affinity, similar to that of the first strains of Sars- CoV-2 isolated at the beginning of the epidemic. In other words, this virus would in theory not need an intermediary animal to infect humans. So does the latter exist? And was he present at the Wuhan market? Two questions still unanswered. Which makes Etienne Decroly say that in the current state of our knowledge, and the data available to researchers, “we are doing science on quicksand”.

Going forward, the scientists behind the two studies stress that it is important to understand where the animals sold in the Wuhan market came from, in order to minimize future risks. Understanding how this pandemic started is crucial to help prevent similar future events, and potentially save millions of lives. In the wake of these two publications, the technical manager at the World Health Organization (WHO) for the management of the Covid-19 epidemic, Maria Van Kerkhove, however welcomed: “It is essential that we continue to studying the origins of the pandemic to ensure we are better prepared to prevent and mitigate future outbreaks and pandemics,” she tweeted. And Kristian Andersen said: “The big question we have to ask ourselves is this: the next time this happens, because it will happen, how do we move from early detection of this epidemic to prevention of this epidemic in order to that it does not become a pandemic?

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In the meantime, none of the hypotheses still on the table are 100% proven. And there is no indication that we will ever know the truth.


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