The COVID-19 pandemic didn’t start at the Huanan market – nor did Eddie Holmes see raccoon dogs?

The scientists thought the virus that causes COVID-19 had a common ancestor with bat coronaviruses. But finding the direct ancestor of SARS-CoV-2 is very unlikely, say researchers.

The approach is a clever one. It gives you the clearest signal of evolution. He points out, however, that some fragments were quite short, which makes those estimates less reliable because there are only a limited number of RNA nucleotides to compare.

The Wall Street Journal added to that debate this week when they reported that the U.S. Department of Energy has shifted its stance on the origin of COVID. The most probable source of the Pandemic was a laboratory leak in China.

The agency was able to conclude that the evidence wasn’t available to the public. The federal government says that the information used in the analysis is “shrivell, questionable, fragmented, or that solid analytical conclusions cannot be inferred from the information.”

The new study doesn’t confirm if animals were carrying the virus. Some researchers say that the hypothesis that the outbreak had an animal origin is vindicated by the fact that animals were present at the market.

“Many other news outlets are presenting this as proof that the lab origin hypothesis is true, and that is a misrepresentation of the evidence for either,” he wrote in the email.

What’s even weirder — it turns out that one of the co-authors of the study, Eddie Holmes, had been taken to the Huanan market several years before the pandemic and shown raccoon dogs in one of the stalls. He was told, “This is the kind of place that has the ingredients for cross-species transmission of dangerous pathogens.”

The data in the 2022 studies paints an incredibly detailed picture of the early days of the pandemic. Photographic and genetic data pinpoint a specific stall at the market where the coronavirus likely was transmitted from an animal into people. And a genetic analysis estimates the time, within weeks, when not just one but two spillovers occurred. The coronaviruses jumped into people in late November or early December and then again within a few weeks.

So if the pandemic didn’t start at the market, one of the first five or 10 people infected in the world was at the market. How do you explain that?

The live animals in the market were, of course, animals from the wild. We have photographic evidence from December. A customer took pictures and videos of the market and then uploaded them to Weibo, which is against the law to sell live animals. The photos were promptly scrubbed. A CNN reporter communicated with the person who took the photos. I was able to get in touch with this reporter, and they passed on those photos from the source. We do not verify the photos completely.

We analyzed a report from the Chinese CDC showing the results of the environmental sampling. The World Health Organization’s report matched a lot of the findings in the report. There was more information in the report that was leaked. There was much more to it than just how many samples in a given stall yielded positive results.

We checked the coordinates on his camera and found that he took a photo at the same stall where five samples tested positive for the disease.

You don’t have a chance of linking early cases to the location where the outbreak started with a virus, such as the one that causes no symptoms in most people. The virus is going to spread quickly outside of where it started.

And yet, from the clinical observations in Wuhan, around half of the earliest known COVID cases were people directly linked to the seafood market. And the other cases, which aren’t linked through epidemiological data, have an even closer geographical association to the market. The paper shows that.

There are thousands, perhaps 10,000, other places at least as likely, or even more likely, to be the place where a new pathogen shows up. Out of 10,000 places, four places that sell live animals are the one’s that have the first cluster of cases. If you’re not surprised by that, then I don’t think you’re understanding the unlikelihood that that presents.

Step back and think, “Where is the first cluster of a new respiratory infection going to appear in this city?” It could appear at a market. But it could also appear at a school, a university or a meatpacking plant.

I think it is a 1 in 10,000 chance. It’s interesting. We have shown that the chance of clustering cases around the market is 1 in 10 million. [if the market isn’t a source of the virus]. That strong evidence in science, we consider it.

And the data zeroing in on the Huanan market, to me, is as compelling as the data that indicated to John Snow that the water pump was poisoning people who used it. The field of outbreak investigations was launched after John Snow, a doctor in London, helped determine the source of a spike in cholera in the city in the 19th century.

Sometimes you have these rare moments where you’re maybe the only person on Earth who has access to this kind of crucial information. As I just started to figure out that there were more cases around the market than you can expect randomly — I felt that way. Those moments bring a tear to your eye.

On 16 March, The Atlantic first reported on the analysis. The release of the full Zenodo work publicly is the first time that this has happened, and it could lead to studies such as where the animals in the market come from.

The researchers were specifically interested in looking for evidence of mammals, which could have been intermediate hosts of the virus. They identified near-complete mitochondrial DNA sequences — some 16,000-base-pairs long — for five species of wildlife, including raccoon dog (Nyctereutes procyonoides), Malayan porcupine (Hystrix brachyura), Amur hedgehog (Erinaceus amurensis), masked palm civet (Paguma larvata) and hoary bamboo rat (Rhizomys pruinosus). “It’s remarkable to have a list,” says study co-author Alex Crits-Christoph, who is a computational biologist at a non-profit organization, and is based in Baltimore, Maryland.

“These data do not provide a definitive answer to the question of how the pandemic began,” said Tedros Adhanom Ghebreyesus, director-general of the World Health Organization (WHO), at a press event on 17 March, after he had been briefed in advance of the report’s release. “But every piece of data is important in moving us closer to that answer,” he said.

The preprint paper written by George Gao2 was originally posted on Research Square in February of 2022, the same month the swabs were discovered. Researchers have asked for that data to be made public on several occasions, without success.

Florence Débarre, an evolutionary Biologist at the French National Center for Scientific Research, found the data in the public data repository on 4 March. “Basically, [they’re] the ones we’ve been waiting for, for a year,” she says.

According to an e-mail from a person at the institution, it does not destroy records, but that contributors often update their records, and thatrecords become temporarily invisible during that time. The market-swab data “are currently being updated with newer and additional data as part of a manuscript currently under review”. (The Gao paper is marked as ‘under review’ at Nature Portfolio Nature’s news team is independent of its publisher Springer Nature, which publishes Nature Portfolio.)

The China CDC refused to collaborate with the authors of the preprint on the analysis. On 14 March, her colleagues, as well as members of the China CDC, presented their work to the WHO at a meeting of the Scientific Advisory Group for the Origins of Novel Pathogens, a body tasked with investigating outbreaks, including the origins of SARS-CoV-2.

At the WHO press briefing on 17 March, Tedros called on the China CDC researchers to be transparent in sharing data. He said that the data could have been shared three years ago.

Débarre recognizes that it has taken a long time to share this data, but acknowledges the environmental sampling and sequencing work conducted by the China CDC. “They did what needed to be done,” she says. If it was not for their work, we wouldn’t have this data.

The data could still be used to create more forensic insights, if they were public again. For example, by looking at the ratio of RNA to DNA for different animal species, researchers could determine how recently those animals were present at the market, because DNA typically persists in the environment longer than RNA does. But more details are needed about how the samples were collected, processed and sequenced, says Wertheim.

A close study of the RNA data could possibly determine whether the animals at the market were sick, adds Crits-Christoph. Does it seem like the creatures were in “a disease state, or a healthy state?” he asks. “There’s all sorts of wonderful, complex questions in the data.”

There are more data that have not yet been shared — including environmental swabs that were negative for SARS-CoV-2, and detailed virus data. Those data are important to analyse, to get a better picture of what was happening at the market, says Wertheim.