Unearthed genetic sequences from China market may point to animal origin of COVID-19

A scientific sleuth in France has identified previously undisclosed genetic data from a food market in Wuhan, China, that she and colleagues say support the theory that coronavirus-infected animals there triggered the COVID-19 pandemic. Several of the researchers presented their findings on Tuesday to the Scientific Advisory Group for the Origins of Novel Pathogens (SAGO), an expert group convened last year by the World Health Organization.

“The data does point even further to a market origin,” says Kristian Andersen, an evolutionary biologist at Scripps Research who attended the meeting and is one of the scientists analyzing the new data. If so, the findings weaken the view of a vocal minority that a virology lab in Wuhan was the likely origin of SARS-CoV-2, perhaps when the coronavirus infected a lab worker, who spread it further.

Florence Débarre, a theoretician who specializes in evolutionary biology and works at the French National Centre for Scientific Research, unearthed the data, which consists of genetic sequences posted in GISAID, a virology database, by Chinese researchers. The Chinese team had collected environmental samples from the Huanan Seafood Market, which was connected to a cluster of early COVID-19 cases and despite its name also sold a variety of mammals for food. Since Débarre spotted the sequences, GISAID has removed them, noting that this was at the request of the submitter.

Given that the mystery of SARS-CoV-2’s origin has been a matter of intense global interest and divisive debate, the data’s discovery and subsequent disappearance will certainly raise questions about why the Chinese team—which includes the former head of China’s Center for Disease Control and Prevention (CDC), George Gao--did not make the sequences public earlier. Contacted by Science , Gao said the sequences are “[n]othing new. It had been known there was illegal animal dealing and this is why the market was immediately shut down.”

But Andersen and his colleagues hope Gao’s team will now make the sequences widely available. “We have urged China CDC and our colleagues there to release this data as soon as possible,” he says.

Gao’s team used swabs to collect environmental samples from many of the stalls of the Huanan market between 1 January, the day it was shut down, and 2 March 2020.  The group  reported last year that some of the samples that tested positive for SARS-CoV-2 also had human genetic material, but no DNA from other animals. The team concluded in a preprint posted on Research Square on 25 February 2022, that this “highly suggests” humans brought the virus to the market—a finding that Gao and co-authors wrote meant the marketplace was not the origin of the pandemic but simply amplified early spread of SARS-CoV-2.

To some Chinese researchers and officials, that scenario suggested the virus originated outside China and somehow found its way to Wuhan. To lab leak supporters, it implied the pandemic might have started at the Wuhan lab.

The study has not yet been published in a peer-reviewed journal, and Science first reported last year that some scientists questioned why a graph in the preprint seemed to show that animal sequences had been found in the market’s virus-positive environment samples, but offered no data of their identity. The analysis presented to the WHO panel this week now suggest that some coronavirus-positive samples collected contained DNA or RNA from raccoon dogs, civets, and other mammals now known to be highly susceptible to SARS-CoV-2.

A caged raccoon dog
Edward Holmes visited the Huanan Seafood Market in 2014 and took this photo of a raccoon dog for sale. New evidence he helped analyze suggests the location had both SARS-CoV-2 and this susceptible species. Edward C. Holmes

Débarre says that on 4 March she “randomly” came across the previously unknown sequence data,  while doing other research on GISAID. It took her five days to recognize that extent of data available and its potential importance.

Débarre quickly reached out about  the  genetic sequences to Andersen and other co-authors  of two preprints posted in February 2022 that supported the marketplace origin theory, papers she says helped shift her away from the laboratory leak origin to thinking the virus likely came from animals at the Huanan Seafood Market. Michael Worobey, an evolutionary biologist at the University of Arizona who was a lead author of the one of the papers, says he and his collaborators still are analyzing the new genetic information, but it has so far solidified his own view that SARS-CoV-2 had a zoonotic origin. (The two preprints on which he is a coauthor were later published by Science .)

“Flo and I have been traveling the same road of being very open to lab leak ideas, but becoming more and more convinced as more and more evidence comes in that’s just not how it happened, and that it did happen at the Huanan market via the wildlife trade,” Worobey tells ScienceInsider .

Worobey also attended the SAGO meeting with Andersen and virologist Edward Holmes of the University of Sydney, who captured a picture of a raccoon dog for sale in the Huanan market in 2014. (China denied the market traded in live mammals until a June 2021 paper documented their sale for 2 years preceding the pandemic.) “We are hoping to be able to talk more about our analyses once they’re completely wrapped up very soon,” says Worobey.

The group says they reached out to Gao and colleagues to collaborate on analyzing the unearthed market sequences, and soon after that the data disappeared from GISAID. When Science asked Gao why GISAID removed the sequence data, he did not reply, but he indicated that the data did not resolve the question of SARS-CoV-2's origin, which he said is "still scientific and open."

The team’s preprint recently had its status on ResearchSquare—which is linked to the Nature family of journals—change from “posted” to “under review" . Journals often require data deposition before publication, so an imminent publication might originally have prompted Gao’s team to submit the data to GISAID.

Missing data?

Chinese researchers in February 2022 posted a preprint that presented this graph to show that several environmental samples from the market containing SARS-CoV-2 also had human genetic material, but offered no data about viral samples that were mixed with other animal species.

A graph plotting environmental genetic samples from the Huanan Seafood Wholesale Market
G. Gao et al ., Research Square, 25 February 2022, https://doi.org/10.21203/rs.3.rs-1370392/v1

Débarre and colleagues plan to post a report of their findings once their analysis is complete, but they hope that the Chinese researchers will revise their preprint to include the full sequence data from the Huanan market and repost it first. “As scientists, we can work together on this,” says Andersen.

Andersen adds that he does not expect the new data to convince everyone that the virus originated at the market. He suspects some people may interpret the new information to mean simply that humans infected with SARS-CoV-2 transmitted the virus to the animals at the market.

Joel Wertheim, an evolutionary biologist at the University of California at San Diego who is collaborating with Andersen and others in the analyses of the newly discovered sequences, says some critics of the spillover hypothesis want more conclusive evidence than science can possibly deliver. “You can’t observe the zoonotic transmission of a novel virus from animals to humans,” says Wertheim. “We’re just never going to get that level of data.”