It was five years ago, an eternity. At the end of 2019, the first human cases of pneumonia of unknown origin were reported in the city of Wuhan, China. A new coronavirus called Sars-CoV-2 was quickly identified as the cause of this disease. We know what happened next, with a pandemic that officially killed more than 7 million people worldwide, even if its true toll seems much higher. However, the elements that led to the emergence of the virus remain mysterious. The investigation into the origins of Covid-19 has not yet revealed all its secrets, but it keeps coming back into the news as discoveries are made. This Thursday, September 19, a new piece is added to the puzzle.
An international study published in the scientific journal Cell proves, through the analysis of different datasets shared on public databases, the presence of wild animals, including raccoon dogs and civets, in the Wuhan market, considered the epicenter of the epidemic, at the end of 2019. This is important because this point has been discussed at length since the first months of the pandemic. It was initially claimed that certain species were sold in this busy place, but the report of the joint WHO-China investigation mission published in 2021 did not mention their presence at the end of 2019. “Today, there is no longer any doubt,” emphasizes Florence Débarre, research director at the CNRS and one of the authors of the study. And this matters because we know, and this since the SARS epidemic in 2000, that raccoon dogs and civets pose a risk for the transmission of coronavirus to humans.”
One stand in particular, in the southwest of the market, caught the attention of researchers because it contained traces of wild species as well as Sars-CoV-2. “This is what we would expect to find if certain animals had been infected. However, we cannot formally prove that they were indeed infected at that time, nor that they were not carriers of the virus. Quite simply because they were not sampled during the first samples taken by the Chinese teams,” continues Florence Débarre. Indeed, at first light on January 1, 2020, when the samplers arrived at the market, which had been closed for just a few hours, the wild animals had disappeared.
Virologist Etienne Decroly, research director at the CNRS in Marseille, welcomes this work which formally demonstrates the presence of these small mammals considered as potential intermediate hosts for Sars-CoV-2. But he points out another element: “If we had an epizootic in the civet or the raccoon dog, for example, we would expect to see many fragments of the virus genome in the samples of these species, and very few in other animals also present on the market. However, there is very little quantity of virus in the samples of raccoon dogs and civets analyzed. It is not because we find civet DNA in these samples that we can conclude that they were infected and were secreting the progenitor virus at the origin of the Covid-19 epidemic.” An analysis that Florence Débarre does not share: “The fact that there are very few viruses is on the contrary in favor of the hypothesis that the animals were indeed infected because the RNA degrades over time. This therefore suggests that the deposit was old, which is what we would expect if the animals were indeed the source of the contamination rather than the humans who would have been infected subsequently”. In any case, adds the researcher: “We cannot affirm in the current state of our knowledge that it was these animals that infected the humans, or the other way around”. The question of the intermediate animal or animals therefore remains unanswered.
Raccoon dogs were being sold in Wuhan market in late 2019, around the time the COVID-19 outbreak began, a new study shows.
© / Marc – stock.adobe.com
Southern China, key to the investigation?
Another aspect of this study concerns the evolutionary history of Sars-CoV-2. Some sequences of the virus were able to be reconstructed from samples taken from the market in early 2020 in order to understand what steps took place at the very beginning of the epidemic. Today, the one called “lineage B” has taken over, giving rise to the many variants since “alpha”, first detected in October 2020. But at the beginning, in Wuhan, there was also a “lineage A”, different by only two mutations and which looks more like bat viruses, which suggested that it was older. Initially, the latter had not been associated with the market, and this posed a problem in a scenario of origin linked to this place. In 2022, a study led by the Chinese George Gao “announced that A had been identified in an environmental sample of the market. This made it possible to make this scenario compatible with the available data. We are adding our stone to this building by confirming this result, and by specifying its importance”, assures Florence Débarre.
More than two years later, the two hypotheses pointed out by George Gao remain relevant: the market is the source of primary contamination with a zoonotic transfer; or the market is a place where there was an amplification of the epidemic without there having been a crossing of species barriers directly on the market. Even today, nothing has been definitively decided even if a bundle of clues appears in the background.
Finally, the study published this Thursday makes it possible to trace the origin of the raccoon dogs present at the end of 2019 on the Wuhan market. According to the analysis of their mitochondrial genomes – a sort of genetic map – the researchers were able to show that they were “probably” from a subspecies present in central and southern China. “This is important because there has been discussion about the possible role of fur farms in northern China in the outbreak of the epidemic,” continues Florence Débarre. Indeed, Sars-CoV-2 has rapidly spread in mink farms, particularly in Denmark, leading to the slaughter of millions of specimens. “But this is also going in the right direction, since the closest viruses (RaTG13 and BANAL) have been identified in the south of the country and in Laos,” adds the researcher.
The fact remains that, despite the analysis of nearly 80,000 samples taken from different farms in China, no trace of the virus’s ancestor has been found in any animal. Perhaps the WHO and Chinese experts did not look hard enough, or in the wrong place. Professor Renaud Piarroux does not believe in the link between the start of the pandemic and the trade in wild animals. “We would therefore have a zoonosis without having identified the slightest ancestor of Sars-CoV-2 in any wild animal, despite the analysis of thousands of sequences from farmed or wild animals. It is also very surprising that a potential animal reservoir suddenly disappeared after the discovery of the first cases in humans because a reservoir is, by nature, perennial. For Marburg fever, we were able to identify the direct progenitor in very difficult-to-access caves in Uganda, but there, nothing,” continues this epidemic specialist. According to him, the market “was a sounding board but not necessarily the starting point of the pandemic.”
“The suspect was at the crime scene, but…”
To sum up, this study does not answer all the questions, but it provides some additional clues to one of the greatest virological mysteries in history. The market played a role, that is now certain, but which one precisely? Small mammals, potential intermediate hosts, were present there, but did they bring the virus with them? So many unanswered questions. “One of the suspects was present at the scene of the crime, that is now certain, but we are not sure that he had the murder weapon on him”, summarizes Etienne Decroly with humor. “We know that there are viruses similar to Sars-CoV-2 circulating in bat populations, which suggests that they are in the first links in the chain,” says Florence Débarre. “Our data allows us to identify the potential last links, in other words what happened at the end of 2019 on the market in Wuhan. What happened between the two, we cannot describe with the data we have. And there are possibly other intermediate species because Sars-CoV-2 is a generalist virus, so not a specialist in humans.”
As for the progenitor virus that caused the Covid-19 pandemic, it is also still running. While some argue that it is found in nature, perhaps in the karst mountains of southern China, others do not dismiss the theory of a research accident out of hand. While we wait for new pieces of this giant puzzle to shed light on our knowledge, we still do not know exactly where Sars-CoV-2 first appeared, or how it was transmitted to humans. The investigation continues.
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