WHO study in Wuhan offers no definitive answers on coronavirus origins

A joint study into the origins of the coronavirus, conducted by experts with the World Health Organization and China, delivered a 316-page report Tuesday, detailing the complex, confusing origins of the pandemic but providing little definitive evidence as to how the coronavirus first emerged.

WHO Director-General Tedros Adhanom Ghebreyesus said during a press conference Tuesday morning it "advances our understanding in important ways," but concluded "I do not believe that this assessment was extensive enough."

The long-delayed report is based around a 28-day visit to the central Chinese city of Wuhan, where the first COVID-19 cases were reported in 2019. It was carried out by a team of 34 experts, including 17 international experts led by the WHO's Peter Ben Embarek, and 17 experts from China. The visit took place in January and February this year, a full year after the virus emerged.

The findings in the expansive document were telegraphed by a press conference conducted on Feb. 9, in which researchers suggested SARS-CoV-2, the virus that causes COVID-19, most likely jumped from a bat to another animal before infecting humans. It also reiterates the stance taken by study members during a press conference in February that a laboratory incident is an "extremely unlikely" pathway for the coronavirus to have entered the human population. 

But the dense, technical report was never going to be a watershed moment in the origins discussion. 

It was designed to be the first phase of a two-phase study, in which international researchers would collaborate with Chinese counterparts to review the early data surrounding the pandemic and plan for a more in-depth mission. Embarek himself has said this wasn't an investigation.

It has also been dogged by questions around interference from Beijing and conflicts of interest in members chosen to be part of the international research team. Ghebreyesus acknowledged on Tuesday the difficulties the team had in "accessing raw data" from China and hoped future studies "include more timely and comprehensive data sharing." 

While the question "where did the coronavirus come from?" remains unanswered, the report details the four scenarios the team propose for its emergence:

1. It directly passed from an animal, such as a bat, to a human
2. It passed from a bat through another species, before infecting humans
   
3. It was introduced through frozen food and the cold-chain
   
4. Or it emerged from a laboratory incident
   

Simplifying things, the report interrogates two opposing locations for SARS-CoV-2's emergence: a wet market and a laboratory. Other global locations are also suggested, but the brunt of the report focuses on how the virus may have emerged via wildlife or frozen food sold at the Huanan Seafood Wholesale Market, a wet market in Wuhan visited by some of the earliest known people with COVID-19, and other markets in the city that sell fresh meat and fish. 

Little data is provided for the opposing scenario, a laboratory incident, but there are interesting takeaways from the 193-page annexes, detailing presentations by researchers at the Wuhan Institute of Virology and extensive sampling of wildlife in different parts of China. We've highlighted some of the key findings below.

Market pressures

Contact with wild animals and livestock can initiate the spillover of viruses from animal to human.

The report discusses much of the sampling and distribution of cases in the Huanan Seafood market and suggests further work is required in studying the supply chains that fed into it (and other Wuhan markets).

Huanan was closed on Jan. 1, 2020, and disinfected, with China's CDC collecting environmental and animal samples on the same day. The WHO-China visit occurred on Jan. 31, 2021, but report the data hasn't yet been analyzed in depth by the joint team due to lack of time. 

The researchers aimed to understand how the virus arrived in, and moved through, Huanan by exploring molecular data, epidemiological data and sampling of animals. Although the Huanan market has been the focus of inquiry, only 28% of early cases had been exposed to just this market, and the very first case had no exposure to the market. 

The attention on the market has largely been on the animals traded there and the wildlife brought in. Several species are known to harbor coronaviruses and one of them may have carried the virus into the market. At least 10 animal stalls sold animals or products including snakes, chickens, ducks, deer, badgers, rabbits, bamboo rats, crocodiles and hedgehogs. Other products were sold frozen and imported from areas across China.

There are several key points regarding the testing data:

• There were 718 environmental samples taken in the Huanan market, and 110 taken from the drainage system. Of those samples, 64 tested positive for SARS-CoV-2.
• There's no evidence of animal infections were discovered from the 188 animals tested. 
• There's no evidence of the sale of live mammals was found in 2019 or during the 2021 visit. 
• Residents interviewed by the team reported never seeing any live animals sold at the market.
• Extensive testing of animal samples in the market and in supply farms all tested negative.
• There's no evidence for association between early cases and specific products sold in the market. 
• It's impossible to tell if a vendor or a customer brought the virus into the market.
• Over 1,100 bats in Hubei province were tested for SARS-CoV-2 and similar viruses, but none tested positive.

On the evidence presented, there appears little reason to suggest Huanan market was the birthplace of the pandemic. With animal samples and vendor suppliers turning up zero positive cases, there's no obvious route for the virus to get into the marketplace. This is the same conclusion that Gao Fu, the director of the Chinese Center for Disease Control and Prevention, came to in May 2020.

Another theory, propagated by Beijing in recent months, suggests cold-chain and frozen food products may have brought SARS-CoV-2 into Wuhan. Flimsy evidence has shown the coronavirus can survive on these surfaces, but there's no compelling example of the cold-chain resulting in COVID-19 infections outside of China. 

In all, the report states "no firm conclusion" can be drawn about the role of the Huanan market in the origin of the outbreak. This doesn't rule out a jump from bat to human, however. Such a leap may have occurred elsewhere or in animals yet to be sampled.

At a seminar in Sydney on Wednesday, Edward Holmes, a virologist from the University of Sydney, suggested both raccoon dogs and minks, which weren't tested in and around Huanan, were good candidates for the missing link the virus needed to jump from bats to humans. Though the 2021 team found no evidence they were in the market, a trip by Holmes in 2014 did reportedly find raccoon dogs at Huanan.

Lab questions

Though the majority of scientists believe the virus leapt from animals to humans and the research team dubbed a laboratory incident "extremely unlikely," there is a growing number of scientists who think SARS-CoV-2 could have accidentally been released from a lab in Wuhan.

The focus in this hypothetical scenario has been on the Wuhan Institute of Virology, a laboratory in the city known to harbor and study a large collection of coronaviruses. 

The research team visited the WIV on Feb. 3, 2021, but that visit isn't mentioned in the final report. Details of the trip can be found over four pages in one of the report's annexes. "They clearly didn't give this a lot of thought," says Nikolai Petrovsky, a vaccine developer from Flinders University in Australia.

Researchers at the WIV, including Shi Zhengli, have been sampling bats across China for over a decade and studying the coronaviruses that lurk within the flying mammals. The research team weren't given access to any data in the laboratory but were provided with an "extensive scientific report" by Shi.

A few key details about the trip show:

• The WIV collected 19,000 samples, with 2,481 testing positive for coronaviruses. 
• A claim all fieldwork is done with full PPE, though this has been contested.
  
• Staff at the WIV, including director Yuan Zhiming, professor Wang Yanyi and virologist Shi Zhengli were questioned, but no raw data was seen.
  
• Yuan Zhiming emphasized the international team's visit could help to defuse some of the conspiracy theories that were circulating.
  
• Staff at the WIV working on coronavirus research all tested negative for SARS-CoV-2 antibodies in April 2019 and March 2020.
  
• A database of coronavirus data, taken offline by the WIV, was attacked more than 3,000 by hackers and taken offline. It remains offline.
  
• Yuan Zhiming "refuted categorically" the rumors of a leak.
  

One of the most pertinent points is the WIV's testing of staff members for SARS-CoV-2. No staff member tested positive for antibodies to the virus, an indicator they had carried the virus. That makes it unclear how a WIV member could have carried the virus out into Wuhan. These tests, according to the report, were performed in March 2020. How quickly antibodies disappear is still up for debate, but recent studies have suggested they persevere for months and, thus, should be detectable at this time.  

Shi also provided information to the team on a spate of mysterious pneumonia cases in mineshaft workers in 2012. The workers cleaned a cave where SARS-CoV-2's closest ancestor, RaTG13, was discovered by the WIV team. Three of the workers died.

The WHO-China team state that, "according to the WIV experts," the miners' mysterious pneumonia was likely explained by fungal infections rather than a coronavirus. This goes against information uncovered by independent researchers where doctors examining the miners suggested they had SARS-like symptoms.

What's next?

Although the report lists a laboratory incident as "extremely unlikely" and deems further study unnecessary, the WHO doesn't see it the same way.

"As far as WHO is concerned, all hypotheses remain on the table," Ghebreyesus said Tuesday. 

Prior to the report's publication, a small group of researchers and scientists, known as the Paris group, published an open letter pre-empting the findings and calling for a "full and unrestricted international forensic investigation" into COVID-19's origins. The group suggests the WHO-China mission had structural limitations making it impossible to fully examine the pandemic's origin. 

They were joined in their concern on Tuesday by 14 governments across the world, including the US, Australia, Canada, Japan and the UK. The nations expressed concern about the transparency in the WHO-China study. 

"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 statement reads. 

During a press briefing on Tuesday, team leader Embarek cited difficulties in obtaining raw data but said the international researchers "were never pressured to remove critical elements in our report."  Others point out a double-standard. The same nations would likely be reluctant to "open their drawers," says Mary-Louise McLaws, an epidemiologist at the University of New South Wales.

Such assurances are unlikely to see the debate around the coronavirus origins end any time soon, however. Jamie Metzl, co-author of the Paris Group open letter, says the team will very likely release another open letter soon. "It's my personal view that the best next step is a new resolution at the World Health Assembly," he notes.

The Assembly, which takes place in May, will likely see discussion around the studies proposed by the WHO-China team that need to take place in phase two. The report suggests further investigation of the supply chain to the Huanan market and other markets in Wuhan is required, in addition to expanding the "geographic range" of surveillance. 

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