The search continues for the origins of the virus that causes COVID-19—and the pathway it took to leap from animals to humans, wreaking havoc across the globe, infecting more than 171 million people and killing more than 3.6 million, as of June 3.
On May 26, the Biden administration directed U.S. intelligence officials to take a closer look at the virus’s origins, including zoonotic transmission—the virus spilling over from another animal to humans—and the possibility of an accidental leak from a laboratory where a wild sample containing SARS-CoV-2 might have been studied.
Until now, the biggest look into the origins of the SARS-CoV-2 virus was a World Health Organization report released on March 30 by a team of international researchers who traveled to China to investigate four possible scenarios in which the SARS-CoV-2 virus might have caused the initial outbreak. In the weeks since, however, world governments have expressed concern that the investigators lacked access to complete data, while scientists say that the report has shed little light on how the virus got jump-started.
Quick and definitive answers are impossible, given that it typically takes years to trace a virus back to its roots—if researchers manage to do so at all, says Angela Rasmussen, a virologist at the Center for Global Health Science and Security at Georgetown University Medical Center. But in this case, she says, “I think we do have enough evidence to say that some are more likely than others.”
In the WHO report, the team found that the virus most likely jumped from one animal to another before making its way to humans. They also looked at evidence supporting theories that the virus passed into humans directly from an original host animal, or that it traveled through the supply chain for frozen and refrigerated foods. In addition, the team addressed the possibility that the virus had been collected in the wild and then accidentally leaked from a laboratory in Wuhan—a scenario they determined is “extremely unlikely.”
The WHO report underscores the virus's likely natural origins, drawing on compelling evidence that SARS-CoV-2 arose in the wild and was not “engineered.” Many scientists, including Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases, have long dismissed the notion that the virus was manufactured. (See Fauci's exclusive interview with National Geographic in which he explained why he thinks SARS-CoV-2 had a natural origin.)
Here’s a look at the evidence the WHO report lays out for each of the four theories—and what experts make of them as possible origin stories for SARS-CoV-2, the virus that causes COVID-19.
1. Direct spillover from animals to humans
WHO ASSESSMENT: possible to likely
The first origin story for SARS-CoV-2 is simple: It suggests that the virus started out in an animal—probably a bat—that came into contact with a human. Boom, infected. At that point, the virus immediately began to spread to other humans.
The WHO report cites strong evidence showing that most coronaviruses that infect humans come from animals, including the virus that caused the SARS epidemic in 2003. Bats are thought to be the most likely culprits, as they host a virus that is genetically related to SARS-CoV-2.
The report acknowledges the possibility that the virus spread to humans from pangolins or minks. But David Robertson, head of viral genomics and bioinformatics at the University of Glasgow, says the WHO joint team sampled many animal species beyond bats for the report. The analyses point to bats as the reservoir species.
“So what you have to worry about then is how did it get from bats to humans?” Robertson says. “Did somebody go into an area, get infected, and then get a train to Wuhan?”
Direct transmission between bats and humans is possible: Studies have shown that people who live near bat caves in southern China’s Yunnan Province have antibodies to bat coronaviruses. But most humans generally don’t spend much time around bats, unless they are bat scientists (who typically wear protective equipment). So it’s unclear why, if the virus jumped from bats directly to humans, the first outbreak would have occurred in Wuhan, a thousand miles away from the bat caves of Yunnan.
Furthermore, the report notes that it would take decades for even the closely related bat coronavirus to evolve into SARS-CoV-2. Since scientists haven’t found a bat virus that would provide the missing link, the WHO team assessed this theory as “possible to likely.”
2. Spillover from animals to humans through an intermediate host
WHO ASSESSMENT: likely to very likely
In the absence of a smoking gun showing that bats passed the virus directly to humans, scientists believe the more likely theory is that the virus first traveled through another animal, such as a mink or a pangolin. Unlike bats, these animals have regular contact with humans—particularly if they’re being raised on a farm or trafficked in the illegal wildlife trade.
If the virus jumped first to another animal, that might also explain how it adapted to be harmful to humans—although Robertson says that the virus likely wouldn’t have had to change much. Genomic analyses suggest that SARS-CoV-2 is a generalist virus rather than one specifically adapted to humans, explaining why it can easily jump among pangolins, mink, cats, and other species.
The WHO report points out that this is the path that previous coronaviruses have taken to infect humans. The SARS virus, for example, is thought to have passed from bats to palm civets before causing a human epidemic in 2002. Meanwhile, the virus that causes MERS has been found in dromedary camels throughout the Middle East.
Daniel Lucey, an adjunct professor of infectious diseases at Georgetown University Medical Center, says that the similarities between SARS-CoV-2 and its relatives SARS and MERS is a compelling argument that it might have started out the same way.
“Now we have three coronaviruses that cause pneumonia and systemic illness and death,” he says. “Past is prologue.”
But, if the theory holds true, it’s not clear what that intermediary animal might have been for SARS-CoV-2. The WHO team analyzed samples from thousands of farmed animals across China, all of which tested negative for the virus. Lucey argues that the WHO team didn’t adequately test China’s farmed mink—one of the suspected intermediaries—but Rasmussen says the report itself acknowledges that it only scratches the surface.
“That’s a fraction of the animals that are farmed or captured or transported for this purpose in China,” she says. “I think we haven’t done anywhere near enough sampling.”
3. Introduction through refrigerated or frozen foods
WHO ASSESSMENT: possible
Another theory holds that the virus may have come to humans through what’s known as the cold chain—the supply line for distributing frozen and refrigerated foods. In this scenario, the virus might have actually originated outside of China but was imported either on the surface of food packaging or in the food itself.
Still, while the cold chain might have played a role in new outbreaks, scientists say there’s little reason to believe that it was the source of the pandemic. There’s no direct evidence that SARS-CoV-2 is responsible for foodborne outbreaks, while Rasmussen notes that COVID-19 rarely spreads through surfaces—which was good news for those weary of wiping down their groceries.
“It’s not impossible,” she says. “You can’t rule it out. But I don’t think the evidence base is particularly strong for that.”
Rasmussen says a more plausible way that the virus might spread through the food chain would be through wildlife that’s farmed for human consumption. But, she points out, that bleeds over into the territory of the theory for an intermediate host.
Some critics claim that this theory is a red herring to push suspicion from China and onto other countries. Lucey considers this pathway the least likely of the four the joint team identified, arguing it’s implausible that the virus would have stayed viable on the packaging for as long as it took to import from Europe or elsewhere. He also questions why these infections would have turned up in Wuhan and nowhere else.
“To me, it’s beyond far-fetched,” he says.
4. Laboratory leak
WHO ASSESSMENT: extremely unlikely
The most controversial hypothesis for the origin of SARS-CoV-2 is that the virus leaked out of a laboratory in Wuhan where researchers study bat coronaviruses. Scientists point out that for now, the evidence both for and against the accidental lab leak hypothesis is thin, but past coronavirus epidemics such as SARS and MERS occurred naturally via zoonotic transmission.
There are two versions of the lab-leak idea: that a researcher was accidentally infected in the lab, or that researchers intentionally manipulated a coronavirus strain to create SARS-CoV-2. Researchers have roundly debunked the latter idea—that SARS-CoV-2 was manufactured—since genetic evidence shows that the virus arose naturally. The WHO focused on the possibility that the virus accidentally escaped from a lab in which wild samples were being studied.
Researchers at the Wuhan Institute of Virology have sequenced the bat coronavirus strain—called CoV RaTG13, which is 96.2 percent similar to SARS-CoV-2, and its closest known relative—as part of their effort to prevent zoonotic viruses from spilling over to humans. A separate laboratory run by the Wuhan Center for Disease Control and Prevention has also worked with bat coronaviruses.
Although there have been laboratory leaks in the past, the WHO report points out that they’re rare. According to the WHO report, there is no record that any Wuhan laboratory was working with a virus more closely related to SARS-CoV-2 before the first cases of COVID-19 were diagnosed in December 2019, nor did any laboratory staff report any COVID-like symptoms suggesting that they had been infected.
On May 23, the Wall Street Journal reported that the U.S. had raw intelligence saying three researchers from the Wuhan Institute of Virology had sought hospital care in November 2019, which may have informed claims made by the Trump administration’s State Department in January. However, the State Department also noted that the Wuhan researchers’ symptoms were “consistent with both COVID-19 and common seasonal illnesses.”
Speaking in April, when the WHO report was released, Lucey said he believes the theory is plausible, though less likely than zoonotic transmission, given the lack of evidence. He points out that there was no forensic investigation of the labs in Wuhan, and he questions why the WHO authorized the team to investigate the lab at all without the mandate to conduct such an investigation or team members with the subject-matter expertise to carry it out.
“There’s not really any way to prove or disprove the lab leak theory based on what’s been presented in this report,” Rasmussen agreed at the time, noting that to put the matter to rest there would need to be a forensic audit of lab records to look for the ancestral virus to SARS-COV-2. “But my opinion is that the lab leak theory, while not impossible, is less likely to be the explanation.”
Rasmussen explains that there’s no evidence that SARS-CoV-2 is the result of genetic manipulation, nor is it likely that it could have been created by accident. It’s incredibly difficult to culture a virus that’s strong enough to cause human infections from a bat sample, she says. Meanwhile, similar viruses commonly occur in nature, making that the far likelier source.
Robertson says that supporters of the lab leak theory argue that SARS-CoV-2 has traveled too quickly and efficiently through the human population to be natural in origin. But if the virus is a generalist, as genomic studies show, he says it’s not surprising that it is so effective at infecting humans.
“I think the evidence is pretty good that it didn’t have to change much to be successful in humans,” he says.
A research roadmap
Although the WHO report may not have shed much light on the origins of SARS-CoV-2, Robertson says this is just the beginning of what can sometimes be a long process. But he says there’s a public health imperative now to launch more rigorous follow-up studies.
“There’s a virus somewhere out there that’s very close to SARS-CoV-2,” he says. “That seems to be the bit that’s terrifying.”
Rasmussen says that the WHO report lays out a roadmap for further studies to discover the origins of the virus. It recommends better surveillance of captive and farmed animals to determine potential reservoir or intermediate hosts, as well as more sampling among bats—both in China and beyond, as there is also evidence of related coronaviruses circulating in regions such as Southeast Asia. The report also recommends in-depth epidemiological studies of the first COVID-19 cases.
Understanding how an outbreak got started helps scientists and governments pinpoint how to strengthen protections—whether that’s more rigorous surveillance for infections in animals and the food chain, or tighter biosafety protocols in laboratories.
“There’s a popular perception that we need some kind of justice or explanation, and somebody needs to answer for this pandemic,” Rasmussen says. “But the real reason why we need to figure out the origin is so that it can inform our efforts to prevent another pandemic like this from happening.”
Editor’s Note: This story has been updated to include the latest information related to the question of whether SARS-CoV-2 escaped from a lab. The story originally published on April 2, 2021.