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Pair of studies say COVID originated in Wuhan market


By Carl Zimmer and Benjamin Mueller


Scientists released a pair of extensive studies over the weekend that point to a large food and live animal market in Wuhan, China, as the origin of the coronavirus pandemic.


Analyzing a wide range of data, including virus genes, maps of market stalls and the social media activity of early COVID-19 patients across Wuhan, the scientists concluded that the coronavirus was very likely present in live mammals sold at the Huanan Seafood Wholesale Market in late 2019 and suggested that the virus spilled over into people working or shopping there on two separate occasions.


The studies, which together span 150 pages, are a significant salvo in the debate over the beginnings of a pandemic that has killed nearly 6 million people across the world. The question of whether the outbreak began with a spillover from wildlife sold at the market, a leak from a Wuhan virology lab or some other event has given rise to pitched debates over how best to stop the next pandemic.


“When you look at all of the evidence together, it’s an extraordinarily clear picture that the pandemic started at the Huanan market,” said Michael Worobey, an evolutionary biologist at the University of Arizona and a co-author of both new studies.


Several independent scientists said that the studies, which have not yet been published in a scientific journal, presented a compelling and rigorous new analysis of available data.


But others pointed to some gaps that still remained. The new papers did not, for example, identify an animal at the market that spread the virus to humans.


“I think what they’re arguing could be true,” said Jesse Bloom, a virus expert at the Fred Hutchinson Cancer Research Center. “But I don’t think the quality of the data is sufficient to say that any of these scenarios are true with confidence.”


In a separate study published online Friday, scientists at the Chinese Center for Disease Control and Prevention analyzed genetic traces of the earliest environmental samples collected at the market, in January 2020.


By the time Chinese researchers arrived to collect these samples, police had shut down and disinfected the market because a number of people linked to it had become sick with what would later be recognized as COVID. No live market animals were left.


The researchers swabbed walls, floors and other surfaces inside the market, as well as meat still in freezers and refrigerators. They also caught mice and stray cats and dogs around the market to test them, while also testing the contents of the sewers outside. The researchers then analyzed the samples for genetic traces of coronaviruses that may have been shed by people or animals.


Although the Chinese researchers conducted their study over two years ago, it was not until Friday’s report that they publicly shared their results. They reported that the Huanan market samples included two evolutionary branches of the virus, known as lineages A and B, both of which had been circulating in early COVID cases in China.


These findings came as a surprise. In the early days of the pandemic in China, the only COVID cases linked to the market appeared to be Lineage B. And because Lineage B seemed to have evolved after Lineage A, some researchers suggested that the virus arrived at the market only after spreading around Wuhan.


But that logic is upended by the new Chinese study, which finds both lineages in market samples. The findings are consistent with the scenario that Worobey and his colleagues put forward, in which at least two spillover events occurred at the market.


“The beauty of it is how simply it all adds up now,” said Jeremy Kamil, a virus expert at Louisiana State University Health Shreveport, who was not involved in the new studies.


Mapping Cases


Although the Huanan market was an early object of suspicion, by the spring of 2020 senior members of the Trump administration were promoting the idea that the new coronavirus had escaped from the Wuhan Institute of Virology, a coronavirus laboratory located 8 miles away on the other side of the Yangtze River.


There’s no direct evidence that the new coronavirus, SARS-CoV-2, was present at the lab before the pandemic. Researchers there have denied claims of a lab leak.


In January 2021, a team of experts chosen by the World Health Organization traveled to China to investigate. Collaborating with Chinese experts, the group released a report in March 2021 that contained previously undisclosed details about the market. They noted, for example, that 10 stalls in the southwest corner of the market sold live animals.


The report also noted that 69 environmental samples collected from the market by the Chinese CDC had turned up positive for SARS-CoV-2. But the frozen meat and live animals had all tested negative.


Still, the WHO left many researchers dissatisfied. Worobey and Bloom signed a letter, along with 16 other scientists in May 2021, calling for more investigation into the origins of COVID — including the possibility that SARS-CoV-2 had escaped from a lab.


The WHO experts had identified 164 cases of COVID-19 in Wuhan over the course of December 2019. Unfortunately, the cases were marked by fuzzy dots scattered across a nearly featureless map of Wuhan.


Worobey and his colleagues used mapping tools to estimate the longitude and latitude locations of 156 of those cases. The highest density of December cases centered around the market — a relatively tiny spot in a city of 11 million people. Those cases included not just people who were initially linked to the market, but others who lived in the surrounding neighborhood.


The researchers then mapped cases from January and February of 2020. They drew upon data collected by Chinese researchers from Weibo, a social media app that created a channel for people with COVID to seek medical help. The 737 cases pulled from Weibo were concentrated away from the market, in other parts of central Wuhan with high populations of elderly residents, the study found.


These patterns pointed to the market as the origin of the outbreak, Worobey and his colleagues concluded. The researchers ran tests that showed it was extremely unlikely that such a pattern could be produced merely by chance.


“It’s very strong statistical evidence that this is no coincidence,” Worobey said.


But David Relman, a microbiologist at Stanford University, raised the possibility that these patterns might be just evidence that the market boosted the epidemic after the virus started spreading in humans somewhere else.


“The virus would have arrived in a person, who then infected other people,” he said. “And the neighborhood of the market, or the market itself, became a kind of a sustained superspreader event.”


Multiple Spillovers


Worobey and his colleagues argue against that possibility, pointing to signs of spillovers within the market itself.


The researchers reconstructed the floor plan of the Huanan market based on the WHO report, the leaked Chinese CDC study and other sources. They then mapped the locations of positive environmental samples, finding that they clustered in the area where live animals were sold.


Strikingly, five of the samples came from a single stall. That stall had been visited in 2014 by one of the co-authors of the new studies, Edward Holmes, a virus expert at the University of Sydney. On that trip, he had taken a photograph of a cage of raccoon dogs for sale at the time.


Another co-author, Chris Newman, a wildlife biologist at the University of Oxford, was part of a research team that documented a number of live, wild mammals for sale at the Huanan market in November and December of 2019, including raccoon dogs.


Worobey and his colleagues also carried out a new analysis of more than 800 coronaviruses sampled from early COVID cases. They found that both Lineage A and Lineage B underwent separate bursts of explosive growth.


The most likely explanation for their results, they concluded, is that Lineage A and Lineage B each jumped on their own from an animal into different people, likely in November.


Both jumps, they said, could have happened at the Huanan market. In their analysis, Worobey and his colleagues found that the two earliest cases of Lineage A involved people who lived close to the market.


New evidence could still emerge. The Chinese government, for example, could release samples taken from Wuhan patients who came down with pneumonia in November 2019, noted Relman of Stanford.


Researchers could also learn more by looking at the genetic samples collected by the Chinese researchers. It’s possible that the samples included genetic material not just from viruses, but from animals at the market. Sharing the raw data could enable other scientists to investigate the potential spillover in more detail.


Kristian Andersen, a virus expert at the Scripps Research Institute in La Jolla, California, and a co-author of the new studies, said it was important to figure out where the wild mammals for sale at Huanan came from, and to look for evidence of past outbreaks in those places. It’s possible, for example, that villagers at the sources of that wildlife still carry antibodies from exposures to coronaviruses.


“If I had to say what would be most helpful to do now, it would be those types of studies,” he said.

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