Science

At the origins of the Covid market in Wuhan? Why isn’t it so easy

What happened between October and December 2019 in the Chinese metropolis of Wuhan, where the first documented cases of Covid-19 were recorded? For almost three years now, the question has been troubling the scientific community. What do we know about the origin of this viral disease that has claimed more than 6 million lives worldwide? After all, very few things. Last June, a panel of distinguished scientists (consisting of experts from the US, China and 25 other countries) convened by the World Health Organization (WHO) presented their findings. They could fit in one sentence: all options on the table, including an accident in the lab. On Tuesday, July 26, two studies published in the prestigious journal Science want to be more positive: The pandemic could have started in the Huanan Seafood Market in Wuhan, indicating an animal origin for the virus. But even here the conditional remains strict.

The first study is a geographic analysis showing that the first cases identified in December 2019 were centered around the market, in contrast to cases reported in subsequent months, which coincided with areas of high population density, indicative of the spread of the virus. In addition, among the recorded cases, a large number of people were likely infected due to proximity to this place, especially those who lived nearby. The researchers also analyzed samples taken from the market in January 2020, such as from a cage or cart. Their analyzes show that samples positive for Sars-CoV-2 were concentrated in the southwest of the market, exactly where live animals (including raccoon dogs, badgers, foxes, etc.) were sold.

The second study is a genomic analysis of the virus from the first cases. She concludes that two lines of the virus, A and B, existed before February 2020. And that the two lines likely originated from two separate cases of human transmission of the virus, both in a market in Wuhan. Previous studies have suggested that the B lineage evolved from the A lineage. Conclusion: It is very unlikely that the virus was widely circulating in humans prior to November 2019.

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In search of an intermediate animal

Do these two studies close questions about the origin of Sars-CoV-2? The answer is no. But they are refocusing the debate around the Wuhan market, which until then had been seen as more of a superspreading site for a virus that had already unfolded elsewhere. In addition, they put aside the trace of a laboratory accident, in particular, associated with the fog that still surrounds the work of the Wuhan Institute of Virology (WIV). Finally, they again put the zoonosis thesis at the center of the game. One of the authors of these studies himself, Michael Sparrow, a virologist at the University of Arizona, 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 then “has made me evolve to the point where today I also think it’s just not plausible that the virus was introduced in any other way than through the animal trade in the Wuhan market,” he said on conferences. press conference. Christian Andersen of the Scripps Research Institute, also a co-author of the study, said: “Have we debunked the lab leak theory? No. Can we ever? probable.”

In fact, these studies take us back three years, when the market was thought to be the origin of the pandemic. “Obviously, this place played a role, but what exactly? An initial element or a superspreader?” Etienne Decroly, a virologist at the CNRS University of Aix-Marseille, is outraged. “If this is an initial element, the origin of a pandemic, then this is due to the search for a precursor virus [NDLR : l’ancêtre commun du Sars-CoV-2] in an animal sold on the market. However, to the best of my knowledge, all the sequencing work done in this market has not been able to get rid of it.” Another difficulty: in order to distinguish the superspread element from the original element, it is necessary, in particular, to analyze the sequences from the beginning of the outbreak. “Unfortunately, we know that some frames are missing. Thus, these two studies, however rigorous they were, were carried out in the context of currently available data, but they are incomplete,” the scientist continues, especially since very quickly and due to the public health emergency, the Chinese authorities devastated and sterilized the market, which made it very difficult to find a possible intermediate animal.

If we focus too much on the Wuhan market, we will almost forget about the work to identify a possible progenitor virus. In September 2021, the closest relative of Sars-CoV-2 was found in a horseshoe bat in Laos. Named BANAL-5, it is 96.85% identical to Sars-CoV-2. Prior to this, the coronavirus closest to it was a strain called RaTG13, whose complete genetic sequence is 96.2% identical to the virus responsible for Covid-19. It was isolated in 2013 at a copper mine in southwest China’s Yunnan province by researchers at the Wuhan Institute of Virology (WIV). “Now we need to fill in the missing links between these viruses present in bats, especially in southwest China, and the first documented infections in Wuhan at the end of 2019. It is also important to understand how the virus acquired an effective ability to spread among people, which is usually associated with sporadic infections detected before the onset of a pandemic, ”declares Etienne Decroly.

“Science on Quicksand”

Another discovery by the Pasteur Institute in Laos showed that BANAL-5 has an RBD (receptor binding domain) capable of binding to the ACE2 receptor of human cells with a 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 theoretically doesn’t need an intermediate animal to infect humans. So does the latter exist? And was it at the market in Wuhan? Two questions remain unanswered. This leads Étienne Decroly to say that with the current state of our knowledge and data available to researchers, “we are doing science on quicksand.”

Going forward, the scientists behind the two studies emphasize 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 began is critical to preventing similar events in the future and possibly saving millions of lives. However, after these two publications, World Health Organization (WHO) Covid-19 technical manager Maria Van Kerkhove welcomed: “It is imperative that we continue to study the origins of the pandemic. so that we are better prepared to prevent and mitigate future outbreaks and pandemics,” she tweeted. And Christian Andersen said: “The big question we have to ask ourselves is this: the next time this happens, because it will happen, how do we go from early detection of this epidemic to prevention of this epidemic so that it does not become a pandemic. ?

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

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