A new analysis of genetic material collected from a live animal market in Wuhan during the early weeks of the COVID-19 pandemic strengthens the hypothesis that the outbreak there began when the coronavirus jumped from infected animals to humans, scientists said.
THE resultsreports the journal Cell, do not identify any specific infected animal that would have brought the SARS-CoV-2 virus to a Chinese city of more than 11 million people. Nor do they definitively prove that the Huanan Seafood Wholesale Market was Ground zero of a pandemic which resulted in more than 7 million dead.
But genetic evidence shows that the market had the conditions necessary to spark an outbreak and makes it increasingly difficult to explain how the coronavirus could have emerged from a lab, a farm or even another of the city’s four live animal markets, the study authors said.
“It’s like a gorilla virus that started in San Diego and first affected people who worked at the San Diego Zoo and lived nearby, and then spread more widely,” said Michael Worobeyan evolutionary biologist at the University of Arizona who worked on the study. “It wouldn’t be hard to deduce that this species most likely came from the zoo’s gorillas.”
The root cause of the pandemic has been hotly debated since its beginning. Wuhan is home to a government lab where scientists study coronaviruses similar to SARS-CoV-2, a fact that has prompted politicians, national security experts, Late Night Talk Show Hosts And many scientists — including Worobey — to question whether the virus had escaped the lab.
As compelling as the argument is, hard evidence to support the leak hypothesis is lacking. In the meantime, new information has come to light convinced scientists with expertise in relevant fields, the virus that causes COVID-19 originated in animals, as did the viruses that cause SARS, MERS and influenza.
The new results continue this trend, he said. Dr Dominic Dwyermember of the international working group which investigation into the origins of the pandemic for the World Health Organization.
“You put all these hypotheses on the table, and some of them become stronger as you get more evidence,” said Dwyer, a medical virologist at the University of Sydney and Westmead Hospital in Australia, who was not involved in the latest work. “This paper has more evidence that supports the animal origin of the virus through the Huanan market.”
The analysis released Thursday draws on genetic data collected from hundreds of samples collected in and around the Huanan market by researchers from the Chinese Center for Disease Control and Prevention shortly after the market closed on Jan. 1, 2020. The Chinese team detected the coronavirus in 74 of the environmental samples they tested, according to their report last year in the journal Nature.
Worobey and his colleagues dug deeper into these data. Using two separate genetic sequencing techniques, they looked for fragments of SARS-CoV-2 as well as DNA from animals and humans.
They then plotted what they found on a map of the vast market, allowing the team to piece together how a few initial infections could have turned into a global health emergency.
Of the 585 samples collected in early January 2020, those that contained the coronavirus were in the southwest part of the market. This is where wild animals were kept in cages to be sold.
“The market is several acres, and this is just one corner of the market and a few stalls,” Dwyer said. “It’s consistent with an animal origin. If it was coming from people walking around the market, you’d find it everywhere.”
One market stall “stood out,” the study authors wrote. It had traces of SARS-CoV-2 in multiple locations: on at least one cart, on a metal container, on the floor, and on a machine used to remove hair and feathers. The researchers dubbed it “wildlife stall A.”
Sixty more samples were taken from the market’s drainage system in late January 2020. Researchers found genetic evidence of the coronavirus in four of them, including one in front of wildlife stall A.
As of mid-February, that drain was still testing positive for SARS-CoV-2, as were two downstream drains that may have been contaminated by runoff from wildlife enclosure A, the researchers wrote.
Samples taken from the stall that contained the coronavirus also contained DNA from a variety of animals, including dogs, rabbits, ashy bamboo rats, Malayan porcupines and masked palm civets. The most abundant DNA came from raccoon dogs, and some was detected in a nearby garbage cart that also tested positive for the virus.
The closest known relatives of SARS-CoV-2 that exist in nature are coronaviruses that circulate in horseshoe bats in southern China, Laos and Vietnam and in pangolins from southern China. But no bat or pangolin DNA was found in any of the samples from the Huanan market.
Raccoon dogs, masked palm civets, white bamboo rats and Malayan porcupines have transmitted bat coronavirus beforethe study authors noted. Could they have done this in Wuhan, they wondered?
Security guards stand in front of the closed Huanan Seafood Wholesale Market in Wuhan on January 11, 2020.
(Noel Celis / AFP via Getty Images)
It is unclear whether bamboo rats or Malayan porcupines can be infected with SARS-CoV-2, the study authors write. There is no strong evidence that masked palm civets can catch the virus, but the animals’ cell lines were susceptible in laboratory experiments.
Raccoon dogs, on the other hand, are known for catch and transmit SARS-CoV-2. And they were the most abundant animal in wildlife stand A.
The researchers analyzed the raccoon dogs’ DNA to see if they might have come from southern China, where they might have crossed paths with bats. They couldn’t say, but they were able to rule out a link to raccoon dogs that lived on fur farms in northern China.
Worobey and his colleagues also studied non-SARS-CoV-2 animal viruses that were detected in wildlife stalls to see if they offered clues about where the infected animals came from.
A kobuvirus that infected civets at the Huanan market was closely related to a virus found in animals sold in Sichuan and Guangxi provinces, which are closer to the range of horseshoe bats and pangolins. And a betacoronavirus that infected bamboo rats had a close relative in a bamboo rat farm in Guangxi, one of two southern provinces where market vendors were known to have sourced the animals.
“These results suggest a movement of infected animals from southern China to Wuhan, a trade channel that may also have led to the emergence of SARS-CoV-2,” the study authors write.
To determine this hypothesis, further investigations will be needed, including fieldwork to collect animal samples in China, he said. Florence DebarreAn evolutionary biologist at the National Center for Scientific Research in Paris and lead author of the study, Worobey said he plans to pursue this line of research.
Dwyer praised efforts to determine where the animals at the market came from – and, by extension, how the virus got to the market.
A second line of evidence also supports the hypothesis that the pandemic had a so-called zoonotic origin, the scientists said.
Among the samples collected from the Huanan market on January 1, 2020, the researchers were able to identify four nearly complete SARS-CoV-2 genomes. One of them belonged to the so-called A lineage, and the other three to the closely related B lineage.
The researchers were unable to determine whether these viruses were shed by animals or people, but the lineage A sample came from a booth where a worker sought medical attention in mid-December 2019. Although this occurred weeks before COVID-19 was recognized as a disease, a World Health Organization report later described the worker as a suspected early patient.
Confirming that both lineages were on the market allowed the team to compare their genomes and work backwards to determine when the two strains diverged and what their most recent common ancestor looked like. They found six candidates, some more plausible than others.
There was a 99% probability that one of the four most likely candidates was right, and all four had something important in common: They were “equivalent or identical” to the most recent common ancestor of the pandemic as a whole, the study leader said. Alexandre Crits-Christophan independent computational microbiologist.
That’s what they would expect if the outbreak had started at the Huanan market, the study authors said. In that scenario, one or more animals infected with the virus would have arrived at the market in November or early December. The virus then spread among animals kept in enclosed spaces indoors, as well as to their human handlers. Those conditions would have given the virus ample opportunity to spread. It took several chances to establish itself among people and begin to spread among its new hosts in a densely populated city.
On the other hand, it is becoming increasingly difficult to piece together all this evidence into a coherent story that the coronavirus entered China. via imported frozen foods (as claimed by the Chinese government) or escape from a virology laboratory with lax biosecurity protocols (as some in the U.S. intelligence community have proposed), Dwyer said.
“We have not added anything to support the lab leak or frozen food theories,” he said. “This only strengthens the animal and market hypothesis.”
Considering that the pandemic started in a city with a virology laboratory where scientists study coronaviruses, it makes sense to ask whether this is more than a coincidence and whether incriminating evidence is being concealed, DéBarre said.
“A lot of us were extremely open to this idea,” she said. “But the data has been piling up and it’s all pointing in the same direction: it’s all pointing to the market.”
“In science, you rarely have definitive answers,” she added. “You say, ‘Given all the data we have, this seems to be the most likely interpretation.'”
