COVID-19 almost certainly did not come from a lab leak. Here’s how we know

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Dr. Angela Rasmussen is a virologist at the University of Saskatchewan’s Vaccine and Infectious Disease Organization, an adjunct professor of biochemistry, microbiology, and immunology at the University of Saskatchewan, and the lead of the host-pathogen interactions pillar for the Canadian Coronavirus Variants Rapid Response Network (CoVaRR-Net). Dr. Michael Worobey is a Canadian evolutionary biologist, and professor and head of the Department of Ecology and Evolutionary Biology at the University of Arizona. They are among the 18 authors of The Huanan Seafood Wholesale Market in Wuhan Was the Early Epicenter of the COVID-19 Pandemic, which was co-led by Dr. Worobey and published in the peer-reviewed academic journal Science.

Since the world first learned about SARS-CoV-2 – the novel coronavirus that would go on to cause the COVID-19 pandemic still raging more than two years later – a major question has gone unanswered: Where did the virus come from? And stemming from that: How did a virus whose closest known relatives circulate in Laos more than 1,000 kilometres away find its way to Wuhan and then the world? Did this virus come from a laboratory, or from nature?

Seemingly, the only thing that people on all sides of the origins question are able to agree on is the need for a robust, independent, evidence-driven investigation. And although attempts were made to seek clarity – including several investigations conducted by governmental officials and international public-health agencies such as the World Health Organization – these efforts have been impeded by incomplete and inaccessible early data, widespread speculation, conflicts of interest, and an increasingly toxic political climate that has undermined scientific expertise and methods.

Now, finally, an international team of virologists, evolutionary biologists and statisticians – of which we are a part – have an answer. Despite some limitations of the evidence base, we applied our scientific training to uncover and meticulously analyze the surprisingly rich data that do exist. In doing so, we can confidently say the pandemic began at the Huanan Wholesale Seafood Market in Wuhan, with all evidence pointing resoundingly at zoonotic spillover (transmission from live animals sold there). These jumps happened at least twice.

Here is how we know.

Because the data about early cases in China is to some degree inaccessible to researchers in other countries, we had to rely on a combination of verifiable pieces of evidence. It was already known that many early cases were linked to Huanan, a large live-animal market west of the Yangtze River in Wuhan, through work or shopping. But not all the early cases had direct ties to Huanan, leading many to speculate that it was possibly an early superspreader event rather than the site of virus emergence.

When we extracted the geographical co-ordinates of the residential locations from the earliest known cases from December, 2019, and plotted them on a map of Wuhan, they clearly formed a clear cluster with the market at the dead centre. This was true regardless of whether an early case had a known link to the market or none at all. This is precisely the pattern that would be expected around the site where community transmission was initially established.

Earlier findings published in the journal Scientific Reports showed live animals susceptible to SARS-CoV-2, such as raccoon dogs and red foxes, were sold across four markets in Wuhan preceding the pandemic. Our team reported they had been present specifically at the Huanan market at the same time the virus began circulating in humans. And we collected other evidence, including business and administrative records, which corroborated that illegal live animal sales were going on at Huanan at the time. Although these animals were evidently not tested for SARS-CoV-2 when the market was closed in January, 2020, a report from the Chinese Center for Disease Control and Prevention did collect environmental samples from various locations in Huanan. Positive samples were overwhelmingly confined to the western part of the market where live animal sales took place, as determined by our analyses of WHO reports, photographs, maps, business records and administrative records detailing fines for illegal live animal sales. Many of these positive samples were collected directly from equipment, such as cages and carts, that were used to house live animals. There were five positive environmental samples alone at a stall where one of our co-authors photographed raccoon dogs being sold in 2014.

While some human-to-human transmission certainly occurred at Huanan, our results revealed that proximity to stalls selling live mammals was as good a predictor of SARS-CoV-2-positive surfaces as proximity to stalls with human COVID-19 cases.

In the earliest days of the pandemic, two distinct genetic variants (known as lineage A and B) circulated in the human population. We showed that both were geographically linked to the market. A preprint analysis (meaning it had not been published or peer-reviewed) from scientists at China’s CDC confirmed that both lineage A and B were found in environmental samples at Huanan. It is our view that there are no tenable scenarios that can explain the presence of both lineages besides two independent zoonotic spillover events. For this to begin as a laboratory accident, one person would have to be infected with lineage B and then immediately go to the Huanan market, then another person would have to be independently infected with lineage A a week later and also immediately go to Huanan market, each leaving no trace at the laboratory or any other location in a city of 11 million people. Such a convoluted scenario is exceedingly unlikely relative to the much simpler explanation: that SARS-CoV-2 was introduced to the human population by two separate zoonotic transmission events at the market itself.

All of this evidence shows that the association of early cases with live animal sales at Huanan market was not a coincidence – but it does not directly address another: Of all the cities in China, the virus emerged in Wuhan, where scientists conducted extensive research on bat coronaviruses at the Wuhan Institute of Virology (WIV). This may seem especially suspicious, given that the most closely related bat coronaviruses known are found far to the south in Laos.

The reason for this is surprisingly simple: Zoonotic spillovers happen much more frequently than people are generally aware. Often, when a virus transmits from an animal to a human, the virus hits a dead end, as it is either unable to replicate efficiently after a species jump or is not passed onward to another human. SARS-CoV-2, however, has demonstrated its ability to replicate efficiently and transmit between many different species. In a densely populated city such as Wuhan, the conditions are ideal for allowing the virus to establish itself in the human population. Drop that same virus into humans in a rural area, and it typically peters out.

SARS-CoV-1 occurred in similar circumstances in late 2002, in another city more than 1,000 kilometres from the nearest bats harbouring SARS-related coronaviruses. It initially emerged in food and animal vendors and was quickly found to infect masked palm civets, raccoon dogs and ferret badgers sold in the markets of Foshan and Guangzhou. It’s true that SARS-CoV-2 was not found in any intermediate species at Huanan – but that is owing to the fact that relevant animals at the market were not tested. And though many questions remain about the provenance of live animals sold at Huanan, investigators at the WIV found SARS-related coronaviruses in farmed civets outside Wuhan in the early 2000s, suggesting that this group of viruses is not confined to far-flung regions of China.

Origin investigations are never quick or easy. The evidence is always incomplete, messy and difficult to access. Ebola virus emerged in 1976 and we still have not identified the exact species of bat responsible for zoonotic spillover in that first outbreak, nor any since. Viruses emerge frequently, sometimes in unexpected places, and it requires significant investments in time, patience and diligent scientific inquiry to pinpoint the circumstances in which they make their way into the human population and begin to spread. Yet, despite the challenges, the evidence base for the origin of SARS-CoV-2 is more robust and conclusive than nearly any other emergent virus in the past century. It is simply stunning, for example, that we have access to the home locations of the earliest known 174 COVID-19 cases in the world. We’ve never had a spatial record like this, of the ignition of any other pandemic, in human history. In conducting this investigation using the data available and the scientific method in which we have been trained, we have shown that the likelihood of SARS-CoV-2 originating anywhere other than the Huanan market is vanishingly slim.

Our work should put to rest the hypothesis that SARS-CoV-2 emerged from a laboratory. To date, the sole evidence supporting a lab origin is the fact that the virus emerged in Wuhan, where WIV is located. However, WIV is not the only laboratory in China – nor, for that matter, in the world – that houses bat coronaviruses. If community transmission began at WIV, we would have seen it at the centre of early cases. We did not. That means WIV is as incidental as any train station, department store or dentist’s office.

From this work, the evidence is clear: Huanan market was the epicentre of this tragic pandemic, and it is virtually certain that the emergence of SARS-CoV-2 was linked to the trade in live wildlife. Anyone who tells you otherwise either doesn’t understand the science, or doesn’t want you to understand it.

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