Two landmark studies investigating the origins of the COVID-19 pandemic have concluded there is overwhelming evidence the SARS-CoV-2 virus spilled over from animals into humans at a live animal market in Wuhan, China. 

Both studies, published in the journal Science Tuesday, were conducted by large teams that included some of the highest profile virologists and disease modellers in the world.

That includes Michael Worobey, a Canadian evolutionary biologist who heads the department of Ecology and Evolutionary Biology at the University of Arizona, and has been a leading scientific voice calling for deeper investigations into the origin of the COVID-19 pandemic.

“There’s a very, very strong case that the Huanan market was indeed the epicentre,” said Worobey shortly after it was published Tuesday. 

The studies refute theories the virus may have originated in a Chinese laboratory, which spread widely over the internet and has gained traction among some politicians.

One of the studies looked at how some of the earliest cases of COVID-19 clustered around Wuhan’s Huanan Seafood Wholesale Market; the other, dug into the genetic history of the virus, pinpointing when and how it made the leap from animals to humans. 

In the first study — led by Worobey with a team of 19 scientists from the United States, Canada, Netherlands, United Kingdom, Belgium and Australia — the researchers drew on data collected from a World Health Organization (WHO) mission investigating the origins of the virus. 

Released in March 2021, the WHO study showed 55 of 168 earliest known COVID-9 cases were associated with the market. But that wasn’t enough to establish that Huanan Seafood Wholesale Market in Wuhan was the epicentre of the pandemic. 

Two months later, Worobey — who is well recognized for investigating the origins of diseases like HIV and the 1918 Spanish flu — was among a handful of scientists who signed a letter calling for investigators to take “both natural and laboratory spillovers seriously until we have sufficient data.”

Pushed by former U.S. President Donald Trump and a handful of U.S. conservative politicians, the theory that the SARS-CoV-2 virus originated in a Wuhan laboratory was revived after The Wall Street Journal published details of a classified report from a U.S. government laboratory that found it plausible and deserved further investigation.

Where did the earliest cases live?

The data Worobey and his colleagues pulled from the WHO report represented the earliest known cases of the virus in Wuhan, a city of roughly 11 million people.

But the WHO report didn’t specify the exact coordinates of each patient’s home. So the researchers overlapped the maps to pinpoint the exact latitude and longitude of each patient.

In order to find further cases radiating out from the market, the researchers layered social media “check-in” data from a Weibo channel created for people with COVID-19 to seek medical help. 

With that information, the team could ask the question: across the 8,000 square kilometres of greater Wuhan where early cases could have emerged, where did they live?

“There was this extraordinary pattern where the highest density of cases was both extremely near to and very centred on this market,” said Worobey. “It was a very, very small area of about, you know, a third of a kilometre squared, with the Huanan market smack dab in the middle.”

Worobey said even when they took away two-thirds of the nearest cases to the market, the results still showed a connection to the market that couldn’t be explained by chance. 

Many of the infected people lived nearby the market but never had any contact with it.

Worobey pointed to a chain of transmission where infected market vendors went into local shops, infecting workers and customers before spreading into a wider population not linked to the market.

The density of the city and its connections with the world was the initial fuel that allowed the pandemic to burn for the past several years, added the Canadian researcher who used to work as a firefighter in B.C.

“You drop the same virus into a rural environment, it just peters out 99 per cent of the time. You drop it into a big city like Wuhan, it then takes off.”

Virus likely jumped to humans twice

In the second Science study, researchers found there were at least two separate cross-species transmission events into humans. 

By analyzing the “molecular clock” of the virus strains and then running a number of simulations, the researchers found there were likely eight but possibly up to two dozen introductions of SARS-CoV-2 preceding its successful transmission in the Wuhan market.

The first successful spillover event likely occurred around Nov. 18, 2019, while the second spillover likely occurred “within weeks of this even,” according to the study led by Jonathan Pekar of the Department of Biomedical Informatics at the University of California San Diego.

The group found it was highly unlikely that SARS-CoV-2 was circulating widely in humans before November 2019.

Kristian Andersen, co-author the Worobey study and a researcher at The Scripps Research Institute’s Department of Immunology and Microbiology, said multiple spillovers of the virus into the human population are not unusual. 

In fact, that’s exactly what happened in 2002 and 2003, when SARS-CoV-1 spilled into humans through the wildlife trade, wet markets and restaurants selling infected animals, he said.

“I was quite convinced of the lab leak myself,” said Andersen, “until we dove into this very carefully and looked at it much closer.”

Moving on from a ‘lab leak’

Worobey’s study also looked inside the market, analyzing environmental samples collected by Chinese scientists in early 2020.

The researchers found the sale of wild animals, like raccoon dogs, badgers, deer and bamboo rats, was clustered in several specific areas of the market where positive virus samples were found in cages and meat cellars.

“There’s lots of other animals that could have brought this particular virus into this market that were infected with this virus,” said Andersen. “We really don’t have clarity on this.”  

“It’s one of these key questions that are absolutely critical.”

That’s because understanding where the infected animals came from could help scientists understand how such zoonotic viruses behave and could spread again in the future. 

Whether on a farm or in the wild, finding out what happened before the virus arrived at the market would also give investigators involved in virus surveillance a place to start looking, says Angela Rasmussen, another co-author and virologist at the Vaccine and Infectious Disease Organization at the University of Saskatchewan.

“This is really what is needed to kind of move on from this whole discussion of ‘Did it come from nature? Did it come from a lab?’” said Rasmussen.

Instead, she says it begs other really important questions, such as: What is the risk another novel coronavirus linked through the trade of animals emerges in people again? 

“All we know is that the animals were brought to the market via a common supply chain and we know which species of animals were at the market, but we don’t have any data currently showing which of those species were infected,” Rasmussen said.

Some of that data could still exist somewhere in China, said Worobey. But to access it will require international collaboration with Chinese scientists, something both Andersen and Rasmussen say has been severed in many cases due to political pressure.

Worobey added that Chinese officials were not fans of either the lab leak theory or evidence that it spread from the Wuhan market. 

Chinese scientists, on the other hand, are big fans of the truth, just like any scientist, said Worobey.

“It’s a bloody lucky thing that the doctors at Xinhua Hospital were so on the ball that they noticed these cases as something unusual at the end of December,” Worobey added. “Chinese data… has been absolutely crucial to getting to the truth.”

While not complete, the evidence the researchers got their hands on is among the best data sets of the early emergence of a global pandemic ever recorded.

What people need to realize, says Rasmussen, “is that by taking all of these different incomplete datasets, and following the threads of evidence where they lead us, they all lead us back to the same point… there are no other alternative explanations.”

International surveillance not keeping up with a changing world

While scientific cooperation with Chinese researchers has been largely severed compared to the start of the pandemic, international surveillance of emerging zoonotic viruses has also stumbled, say the researchers involved in the two studies. 

“I don’t actually think we’re doing better currently than we were at the beginning of the pandemic because again, we downplay the risk of these infectious diseases, we don’t really collaborate,” said Andersen.

“We need transparency and data reporting. We need to have rapid reporting and cooperation. We need to have very strong surveillance systems in place.”

And then there’s the funding, says Rasmussen, which underpins the entire effort to catch emerging diseases before they blow up into a pandemic. 

“There’s still many holes all around the world,” she said, pointing to the emergence of monkeypox. “We’re just not making these investments because they don’t affect people in Canada, they don’t affect people in the U.S., they don’t affect people in Europe — until they do.”

That’s especially important now because the chance humans interact with animals is growing by the year. Climate change and ever-shifting land use patterns are increasingly disrupting ecosystems and forcing many species to find new refuges closer and closer to people, Rasmussen said.

“There are definitely loud voices who are saying that doing surveillance is dangerous, and therefore we should just close our eyes and plug our ears and hope that the viruses don’t get us,” she said. “But the reality is that we live in an increasingly global world.”

“None of those things are going away.”

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