WHO Report Leaves Big Questions About COVID-19 Origins

After a month of gathering information in China, and even longer turning the findings into a 120-page report, an international team of experts on Tuesday delivered its conclusions on the origins of the coronavirus pandemic.

The bottom line: We still don’t know where SARS-CoV-2, the virus that causes COVID-19, came from — and it’s possible we never will.

The most likely explanation, according to experts convened by the World Health Organization and the Chinese government, is that the coronavirus transmitted from its natural animal host to people via an intermediate wild species that was farmed for food. They rated a competing theory that the virus escaped in an accident at a lab in the Chinese city of Wuhan as “extremely unlikely” — but devoted less than two pages of the report to that possibility.

Some scientists criticized the report, which provides new details about what Chinese authorities did to try to find the source of the virus, but leaves many important questions unanswered. Efforts to identify the natural or intermediate animal hosts for the virus have so far drawn a blank.

“We’ve only scratched the surface of this very complex set of studies that needs to be conducted,” Peter Ben Embarek, a WHO food scientist and coleader of the study, said at the launch of the report on Tuesday.

WHO Director-General Tedros Adhanom Ghebreyesus told member countries on Tuesday that the study didn’t adequately analyze the possibility of a lab leak, according to Bloomberg. “As far as WHO is concerned, all hypotheses remain on the table,” Tedros said in a public statement. “This report is a very important beginning, but it is not the end. We have not yet found the source of the virus, and we must continue to follow the science and leave no stone unturned as we do.”

Following the release of the report on Tuesday, the US State Department issued a statement on behalf of the US and 13 other countries, writing, “We voice our shared concerns that the international expert study on the source of the SARS-CoV-2 virus was significantly delayed and lacked access to complete, original data and samples.”

The report was jointly authored by 17 WHO-appointed experts and 17 Chinese scientists. The sites they visited, and the wording of the report, required sign-off from the Chinese government. And, crucially, the study was not the forensic investigation that some scientists have called for — going through freezers, databases, records of field sampling, and lab notes to probe the controversial theory that the virus escaped in an accident at a lab in the city of Wuhan.

This theory emerged in the early days of the pandemic. One prominent member of the WHO–China team, Peter Daszak of the EcoHealth Alliance in New York City, has been among its most vocal opponents. He had collaborated for many years with the Wuhan Institute of Virology, sampling coronaviruses from bats and assessing the threat that they could cause a pandemic. For more than a year, he has described explanations involving a lab release as “conspiracy theories.”

Daszak also found himself at the center of a political storm in April last year. With then-president Donald Trump and his secretary of state, Mike Pompeo, both claiming they had evidence, without providing any details, that the virus came from the Wuhan lab, Daszak’s grant from the National Institutes of Health to collaborate with the agency was abruptly terminated. The resulting political polarization turned the lab origin idea into a third rail that many scientists didn’t want to touch.

Daszak’s close links to the Wuhan Institute of Virology have also led some to question whether this conflict of interest made him a good choice for the WHO team. But he rejected the idea that this undermined his credibility. “If I was to say I’m not going to China and not be involved with this, then I’m not doing my job,” Daszak told BuzzFeed News. “This report has more information and more depth because of having me involved in it.”

Still, given all the obstacles to a full and transparent investigation, some scientists wonder whether we will ever have conclusive answers about the origins of COVID-19.

“I don’t know if we’re ever going to know in more detail than we do now,” said Jesse Bloom, a specialist in viral evolution at the Fred Hutchinson Cancer Research Center in Seattle.

“I still believe that we will find out, but I don’t know when and I don’t know how. And I’m not terribly encouraged by today’s report,” Daniel Lucey, a specialist in infectious diseases at Georgetown University in Washington DC, told BuzzFeed News. “It leaves the great unknown: whether it was natural or not natural.”

Here are the four main theories for the origins of COVID-19 that the WHO–China team considered:

Theory 1: The coronavirus jumped to people via an intermediary species.

This is the explanation favored most strongly by the WHO–China team, rated as “likely to very likely” in the new report.

As the Chinese authorities investigated the initial outbreak in Wuhan in December 2019, scrutiny fell on the city’s Huanan Seafood Market, which was connected to an early cluster of cases. Although the 12-acre site is mainly a seafood market, live animals and frozen meat were also sold at stalls.

After the market was closed at the beginning of January, investigators in full personal protective equipment swabbed every available surface, sampled the remaining carcasses, and even tested sewage from the site. They found widespread evidence of SARS-CoV-2 on surfaces, consistent with contamination by infected people, animals, or animal products, but no evidence of the virus in the remaining animals or carcasses.

Given the evidence that the virus was circulating elsewhere in Wuhan in December 2019, it could well be that the market was contaminated by infected people, rather than being the source of the outbreak.

But if SARS-CoV-2 did infect people via an intermediate species, it would fit with the precedent of two related coronaviruses that have jumped to people, each setting off a global health scare.

SARS, which emerged in South China’s Guangdong province in November 2002, spread to more than two dozen countries, killing 774 people by the end of July 2003. By October that year, very similar viruses had been found in palm civets in live-animal markets in Guangdong. These common catlike carnivores are farmed and sold for food and are now believed to be the intermediate host from which SARS jumped to people.

MERS emerged in Saudi Arabia in September 2012. Cases have since turned up in 27 countries, and the virus has so far killed 882 people. Within a year of the disease’s discovery, scientists had used antibody testing to show that there was widespread infection of dromedary camels in Oman. The virus was later found in camels across the Middle East and Africa, establishing this common domestic animal as the likely intermediary host.

The problem is that no similar smoking gun has yet been found for SARS-CoV-2, even after Chinese scientists ran antibody and genetic tests on tens of thousands of samples from domestic and wild animals.

“More than 80,000 wildlife, livestock and poultry samples were collected from 31 provinces in China and no positive result was identified for SARS-CoV-2 antibody or nucleic acid before and after the SARS-CoV-2 outbreak in China,” the report said.

There was an initial flurry of interest in pangolins, or scaly anteaters, after Chinese scientists pointed to similarities between SARS-CoV-2 and coronaviruses found in a small number of sick pangolins. But with subsequent testing of pangolins, this lead has failed to pan out.

The WHO–China team placed its main bet on the intermediate-host theory because of evidence that meat from animals thought to be susceptible to similar coronaviruses, including bamboo rats, was sold in the Huanan market. The Chinese authorities also provided evidence of supply chains to Wuhan from wild animal farms in several provinces, including Yunnan in southern China.

As the outbreak raged in Wuhan, China cracked down on this trade in February 2020, closing wildlife farms in Yunnan. But these farms were not subjected to the same intense swabbing and sample analysis as the Huanan market — meaning we don’t know what viruses were present there at the time.

“What they didn’t do is a very focused traceback,” said Daszak.

The animals once farmed in South China have long since been killed, and many former wild animal farms have been converted into factories. So the most obvious trail for any subsequent investigation of the intermediate host theory has gone cold.

Still, Daszak and other members of the WHO–China team are optimistic that testing wild animals in the region and running antibody tests on former wildlife farmers will eventually turn up evidence of infection with a virus that closely matches SARS-CoV-2.

“I think it’s absolutely achievable,” Daszak said. “The people who worked in the farms are still there.”

Theory 2: The virus jumped directly from bats to people.

Most scientists believe that SARS-CoV-2 ultimately came from bats, thought to be the natural hosts of SARS-like coronaviruses. If so, it could have spread straight from bats to people.

The new report said that more than 1,100 bats in Hubei province, around the city of Wuhan, had been sampled and tested, “but none were positive for viruses close to SARS-CoV-2.”

The closest known relative of SARS-CoV-2 is a virus called RaTG13, isolated from a horseshoe bat in a mineshaft in Mojiang, Yunnan province, by Shi Zhengli of the Wuhan Institute of Virology in 2013. In a February 2020 paper in Nature, Shi revealed that the genome of RaTG13 was 96% similar to SARS-CoV-2.

This and other bat coronavirus genetic sequence data from the region suggest strongly that the ultimate origin of SARS-CoV-2 is a bat from South China or a neighboring country in Southeast Asia. People in that region are known to get infected by bat viruses: In 2018 Daszak and Shi reported that 6 out of 218 people living near caves with bat roosts in Jinning District, also in Yunnan province, had antibodies to SARS-like bat coronaviruses.

But the 4% difference between RaTG13 and SARS-CoV-2 represents at least a couple of decades of viral evolution, so the two viruses are still far removed from one another. And if SARS-CoV-2 did jump straight from bats to people, it’s hard to explain why the pandemic started in Wuhan, more than 1,000 miles away from the rural areas near China’s southern border, where you would expect the first clusters of human cases to show up.

Theory 3: The virus was accidentally released by a lab studying coronaviruses.

After the initial SARS outbreak, accidental infections of staff happened at labs studying the virus in Singapore, Taiwan, and China, including several at the Chinese National Institute of Virology in Beijing. It’s this history of accidents that makes some scientists question why the WHO–China study team rated the possibility of a lab origin for COVID-19 as “extremely unlikely.”

“It’s reasonable to ask why they’re being so dismissive,” Marc Lipsitch, an epidemiologist at Harvard University, told BuzzFeed News.

Proponents of the idea that the virus escaped from a lab have pointed to unusual features of its genetics and biology.

Over the course of the outbreak of SARS, scientists tracked the virus mutating rapidly as it adapted to its new human hosts. But SARS-CoV-2 burst onto the scene seemingly already perfectly adapted to transmit from one person to another.

For SARS-CoV-2 to get into human cells, the spike protein on its surface must latch onto a receptor on the cells called ACE2. After the first complete genetic sequence of the virus was posted online by Chinese scientists in January 2020, a team led by Nikolai Petrovsky, an immunologist who works on vaccine development at Flinders University near Adelaide in Australia, started running computer simulations of how well the coronavirus spike protein could bind to ACE2 receptors from different species.

“When we got to the end of the project, what stumped us was that binding to human ACE2 was higher than for any species we tested,” Petrovsky told BuzzFeed News. “For us, that was very hard to explain based on a natural origins theory.”

Other scientists focused on part of the spike protein called a “furin cleavage site,” which seems to be an important factor in the ability of SARS-CoV-2 to infect human lung cells — speculating this had been deliberately inserted into the virus to study genetic changes that can make coronaviruses more dangerous to people.

But in March 2020, scientists led by Kristian Andersen of the Scripps Research Institute in La Jolla, California, concluded that the virus didn’t look as if it had been genetically engineered. If so, they argued, you’d expect to see a backbone of a familiar coronavirus used in such experiments with a few key changes. But SARS-CoV-2 has a wide array of mutations throughout its entire genome that separate it from known coronaviruses.

Still, some scientists have continued to speculate that SARS-CoV-2 may have been engineered to study the changes that could make a naturally occurring coronavirus into a pandemic threat. Such “gain-of-function” research has long been controversial because of the risks it could pose.

Suspicion fell on Shi of the Wuhan Institute of Virology, Daszak’s longtime research collaborator because of her previous gain-of-function work. In 2015, she and Ralph Baric, a virologist at the University of North Carolina, Chapel Hill, had published controversial experiments in which they spliced the spike protein from a SARS-like bat coronavirus into another coronavirus that had been previously adapted to infect mice to study the potential for the type of cross-species transmission that could trigger a pandemic.

The lab origin theory was already a political minefield after Trump and Pompeo got involved. And things became even more fraught in fall 2020 when a scientist who had fled to the US from Hong Kong, Yan Limeng, teamed up with a group linked to former Trump strategist Steve Bannon. Yan posted two papers making the incendiary claim that SARS-CoV-2 was an engineered bioweapon deliberately released by the People’s Liberation Army.

Experts overwhelmingly agree that this is a wild conspiracy theory. And many virologists also remain unconvinced by the idea that SARS-CoV-2 was engineered in well-intentioned gain-of-function experiments.

While the furin cleavage site is unusual, Susan Weiss, a coronavirus specialist at the University of Pennsylvania, told BuzzFeed News that experts still don’t understand exactly how specific furin cleavage sites can make viruses more dangerous. “I just don’t buy that any human could figure that out,” she said.

But as the political temperature has dropped in the wake of Trump’s electoral defeat, some scientists have been discussing the lab accident theory more openly. “[I]f SARS-CoV-2 escaped from a lab to cause the pandemic, it will become critical to understand the chain of events and prevent this from happening again,” wrote David Relman, a microbiologist at Stanford University, in an opinion piece published in PNAS, the journal of the National Academy of Sciences, on Election Day.

Shi did not respond to requests for an interview from BuzzFeed News. But the experiment with Baric was conducted in North Carolina, not Wuhan. And in emailed responses to questions from Science magazine in July 2020, Shi flatly denied having run any similar experiments since.

A lab accident doesn’t need to involve genetic engineering, however. Shi’s group has collected thousands of samples from bats across China. Ruling out the idea that COVID-19 arose when a virus escaped from the lab would require the Wuhan institute to open up all the records of its viruses and the audit it performed to investigate whether any one of them was a close match to SARS-CoV-2.

The Chinese government did not allow that to happen. Adding to the impression of secrecy, an online database continuing information on the institute’s genetic sequences and samples seems to have gone dark in September 2019 and hasn’t returned to public view since.

During their visit to the Wuhan institute, members of the WHO–China study team asked questions about the database and the audit of virus samples. They were told the database was removed after multiple hacking attempts.

“Their answers can then be looked at and pulled apart. And that’s what we did,” Daszak said. “There really is no evidence of a lab leak. I’ve not seen it and I’m looking for it.”

Theory 4: The virus was spread via frozen food.

When leaders of the WHO–China team announced their initial conclusions in a press conference on Feb. 9, many scientists were astonished that they were taking this theory seriously. For months, the Chinese authorities had controversially linked renewed outbreaks of COVID-19 in the country to imported frozen seafood. It seemed to be a narrative calculated to promote the idea that the disease may have first emerged abroad.

“We know that the virus can persist and survive in conditions that are found in these cold and frozen environments, but we don’t really understand if the virus can then transmit to humans,” Embarek, the WHO food scientist who led the WHO–China team, said at the February press conference. “So a lot of work needs to be done to better understand these interesting pathways.”

Speaking in an online discussion organized by the UK-based international think tank Chatham House earlier this month, Marion Koopmans, a virologist at the Erasmus University Medical Center in Rotterdam, the Netherlands, said the team was thinking more about frozen wildlife meat rather than frozen seafood — which would link the idea to the intermediate host theory.

“That’s what we think is still a very, very valid option,” Koopmans said.

Many virologists think it’s unlikely that frozen food was the origin for COVID-19, partly because studies of transmission of the virus from surfaces or objects — known as “fomites” — suggest that it’s very inefficient compared to transmission through the air.

“The bottom line is that fomite transmission can happen, but it’s very rare,” Angela Rasmussen, a virologist at Columbia University, told BuzzFeed News.

Even after the WHO–China report, scientists still have more questions than answers about the origins of SARS-CoV-2.

More than a year into the pandemic, and with the biggest effort to pin down its cause having delivered an open verdict, speculation of a lab origin is going to continue. But if anything, the continued demands for further investigation of that possibility are only likely to make the Chinese authorities block further release of information from the Wuhan lab.

“I think that origin story for the virus is much less likely, and the loud demands of that theory’s proponents make it ever less likely that the Chinese government would ever consent to that type of investigation,” Rasmussen said.

In one key respect, Tuesday’s report gives the Chinese authorities exactly what they want: The terms of reference of the study, released in November last year after extensive negotiations between the WHO and China, framed it as the “China Part” of a global study.

Having opened its doors to an international team of experts, China will now likely argue that other countries need to do the same. ●