ABOVE: A raccoon dog (Nyctereutes procyonoides) © iStock.com, Viktor_Kitaykin

Over the weekend (February 25–26), researchers released a trio of studies that add weight to the theory that a live food and animal market in Wuhan, China, is likely the origin of the COVID-19 pandemic.

Two of the studies analyzed viral genomes alongside geospatial maps of the stalls in the Huanan Seafood Wholesale Market, finding that the SARS-CoV-2-positive swabs collected from stalls and food at the market were concentrated in a section of the market where live animals were sold. The third, an analysis of 800 early COVID-19 cases in Wuhan, suggests that the virus spilled over into people at the market on two separate occasions, sometime between November and December 2019.

Kristian Andersen, a virologist at the Scripps Research Institute in La Jolla, California, and an author on two of the reports, tells Nature that the three studies together are “extremely strong evidence” that the market was the source of the coronavirus outbreak. 

None of the studies pinpoint which animal was the original vector for the virus. Andersen speculates that raccoon dogs, a mammal used for food and fur in China, could be the long-sought intermediate host. Raccoon dogs can harbor several coronaviruses. One of the studies shows that raccoon dogs were sold in a section of the market where coronavirus samples were detected, reports Nature.

“It’s very convincing,” Thea Fischer, an epidemiologist at the University of Copenhagen who was not involved in any of the new studies, tells The New York Times. She says that the question of whether the virus spilled over from animals “has now been settled with a very high degree of evidence, and thus confidence.”

See “Theory that Coronavirus Escaped from a Lab Lacks Evidence

In late 2019, after several people who had visited the market became sick with what would later be recognized as COVID-19, Chinese officials ordered the market to be shut down. By the time researchers from the Chinese Centers for Disease Control and Prevention got to the market in January 2020, it had already been shuttered and disinfected, and all the animals had been culled, according to the Times

Even though no live animals were present, researchers still swabbed all of the surfaces in the market and collected samples from any meat still in the freezers and refrigerators, reports the Times. They also trapped and tested stray animals in the area and tested the contents of the sewers outside. The researchers then sequenced all the samples, looking for traces of SARS-CoV-2, according to Nature

A year later, in January 2021, a team of researchers from the World Health Organization (WHO) went to Wuhan to investigate the origins of the COVID-19 pandemic. They collaborated with the Chinese researchers who initially collected the samples in January 2020, and published some previously undisclosed results in a report in March 2021. This WHO report revealed that 188 animals from 18 species sold at the market tested negative for coronavirus, while 1,000 samples taken from surfaces at the market overwhelming tested positive for SARS-CoV-2. 

Meanwhile, the Chinese team continued to perform genetic analyses on the Huanan market samples they had collected and concluded that the samples included two early evolutionary lineages of SARS-CoV-2, which the researchers call A and B, both of which were circulating among early COVID-19 cases in China. Although the sample collection was completed more than two years ago, the Chinese researchers just shared their results Friday as a Nature preprint. 

In a separate study of the market, researchers collected information on the first known COVID-19 cases in China, including data from newspaper articles, photos, and audio and video recordings of patients in Wuhan, and added that to data available in the WHO report. With this information, the researchers completed a geospatial analysis of the first COVID-19 cases in Wuhan, finding that they were initially clustered in and around the market, gradually becoming more dispersed. The researchers also analyzed the locations of the positive samples in the market and cross-referenced the market’s business registration information and examined photographs of the locations. This allowed them to map the largest concentration of positive samples from the market to a single stall that sold live animals, and more specifically, to a metal cage containing a raccoon dog, reports Nature. 

In the third report, the authors report that the two lineages of SARS-CoV-2, A and B, are too genetically different from one another to have diverged from one another in humans. They hypothesize that the coronavirus must have evolved within a nonhuman animal pool and spread to humans on two different occasions, reports Nature. The researchers also analyzed samples from 800 early COVID-19 cases and concluded that Lineage A and Lineage B spread quickly around Wuhan.

Some scientists argue that the studies aren’t sufficient evidence to rule out the controversial counter-hypothesis that the virus first infected humans in a laboratory setting. “I think what they’re arguing could be true,” Jesse Bloom, a virologist at the Fred Hutchinson Cancer Research Center and first author on a letter published in Science in May 2021 arguing for researchers to keep an open mind about the so-called “lab leak hypothesis,” tells the Times. “But I don’t think the quality of the data is sufficient to say that any of these scenarios are true with confidence.”

See “COVID-19’s Origins Need Further Investigation, Say Scientists

Michael Worobley, a coauthor of two of the new preprints, co-signed the letter led by Bloom back in May. “You want to take this kind of thing seriously,” he tells Nature. But given the recent evidence, Worobley says he has changed his mind.  “When you look at all of the evidence, it is clear that this started at the market,” he says.