2021-03-31 03:38:49 WHO Report Leaves Big Questions About COVID-19 Origins

WHO Report Leaves Big Questions About COVID-19 Origins

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

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

According to experts convened by the World Health Organization and the Chinese government, the most likely explanation is that the coronavirus spread 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 only devoted less than two pages of the report to it.

Some scientists criticized the report, which provides new information about what Chinese authorities did to try to find the virus’s origins while leaving many important questions unanswered. Attempts to identify the virus’s natural or intermediate animal hosts have so far yielded no results.

“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 study coleader, said at the report’s release on Tuesday.

According to Bloomberg, WHO Director-General Tedros Adhanom Ghebreyesus told member countries on Tuesday that the study did not adequately analyze the possibility of a lab leak. “All hypotheses remain on the table as far as WHO is concerned,” Tedros said in a public statement. “This report is an important starting point, but it is not the end. We have not yet discovered the virus’s origin, and we must continue to follow the science and leave no stone unturned as we do so.”

Following the report’s release on Tuesday, the US State Department issued a statement on behalf of the US and 13 other countries, writing, “We express our shared concern 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 co-written by 17 WHO-designated experts and 17 Chinese scientists. The locations they visited, as well as the wording of the report, required approval from the Chinese government. And, crucially, the study was not the forensic investigation that some scientists have called for, which would have combed through freezers, databases, field sampling records, and lab notes to investigate the contentious theory that the virus escaped in an accident at a lab in the Chinese city of Wuhan.

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

Daszak was also at the center of a political storm in April of last year. With then-President Donald Trump and Secretary of State Mike Pompeo both claiming, without providing any details, that the virus originated in the Wuhan lab, Daszak’s grant from the National Institutes of Health to collaborate with the agency was abruptly terminated. As a result of the resulting political polarization, the idea of lab origins became a third rail that many scientists refused to touch.

Daszak’s close ties to the Wuhan Institute of Virology have also raised concerns about whether he was a good fit for the WHO team. However, he denied that this harmed his credibility. “If I say I’m not going to China and I’m not involved in this, I’m not doing my job,” Daszak told BuzzFeed News. “Because I was involved in it, this report has more information and depth.”

Nonetheless, given all of the obstacles to a thorough and transparent investigation, some scientists are skeptical that we will ever have definitive answers about the origins of COVID-19.

“I don’t know if we’ll ever know in greater detail than we do now,” said Jesse Bloom, a viral evolution specialist at Seattle’s Fred Hutchinson Cancer Research Center.

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

The WHO–China team considered four major theories for the origins of COVID-19:

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

The WHO–China team prefers this explanation, which is rated as “likely to very likely” in the new report.

As Chinese authorities investigated the initial outbreak in Wuhan in December 2019, the city’s Huanan Seafood Market was linked to an early cluster of cases. Although the 12-acre site is primarily a seafood market, live animals and frozen meat were also available for purchase at stalls.

After the market was closed in early January, investigators in full PPE swabbed every available surface, sampled the remaining carcasses, and even tested sewage from the site. They discovered widespread SARS-CoV-2 contamination on surfaces, consistent with contamination from infected people, animals, or animal products, but no virus in the remaining animals or carcasses.

Given that the virus was still circulating in Wuhan in December 2019, it’s possible that the market was contaminated by infected people rather than being the source of the outbreak.

However, if SARS-CoV-2 infects humans via an intermediate species, it would follow in the footsteps of two related coronaviruses that have jumped to humans, each causing a global health scare.

SARS, which first appeared in South China’s Guangdong province in November 2002, spread to over a dozen countries and killed 774 people by the end of July 2003. By October of that year, very similar viruses had been discovered in palm civets in Guangdong live-animal markets. These common carnivores, which are farmed and sold for food, are now thought to be the intermediate host from which SARS spread to humans.

MERS first appeared in Saudi Arabia in September 2012. Since then, cases have been reported in 27 countries, and the virus has killed 882 people. Within a year of the disease’s discovery, scientists used antibody testing to show that dromedary camels were infected in Oman. Later, the virus was discovered in camels throughout the Middle East and Africa, establishing this common domestic animal as the likely intermediary host.

The problem is that no similar smoking gun for SARS-CoV-2 has yet been discovered, despite the fact that 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 results for SARS-CoV-2 antibody or nucleic acid were identified before or after the SARS-CoV-2 outbreak in China,” according to the report.

Pangolins, also known as scaly anteaters, sparked initial interest after Chinese scientists discovered similarities between SARS-CoV-2 and coronaviruses found in a small number of sick pangolins. However, subsequent pangolin testing has revealed that this lead was not viable.

The WHO–China team bet heavily on the intermediate-host theory, citing evidence that meat from animals suspected of being susceptible to similar coronaviruses, such as bamboo rats, was sold in the Huanan market. The Chinese authorities also provided evidence of supply chains from wild animal farms in several provinces, including Yunnan in southern China, to Wuhan.

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

“What they didn’t do was a very focused traceback,” Daszak explained.

The animals that were once farmed in South China have long been slaughtered, and many of the former wild animal farms have been converted into factories. As a result, the most obvious trail for further investigation of the intermediate host theory has gone cold.

Nonetheless, 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 reveal evidence of infection with a virus similar to SARS-CoV-2.

“I think it’s completely doable,” Daszak said. “The farm workers are still there.”

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

Most scientists believe SARS-CoV-2 originated in bats, which are thought to be the natural hosts of SARS-like coronaviruses. If that’s the case, it could have spread directly from bats to humans.

According to the new report, more than 1,100 bats were sampled and tested in Hubei province, near the city of Wuhan, but “none were positive for viruses similar to SARS-CoV-2.”

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

This and other bat coronavirus genetic sequence data from the region strongly suggest that the ultimate source of SARS-CoV-2 is a bat from South China or a neighboring Southeast Asian country. Bat viruses have been known to infect people in that area: Daszak and Shi reported in 2018 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.

However, the 4% difference between RaTG13 and SARS-CoV-2 represents at least a couple of decades of viral evolution, indicating that the two viruses are still far apart. And, if SARS-CoV-2 did jump directly from bats to humans, it’s difficult to explain why the pandemic began in Wuhan, more than 1,000 miles away from the rural areas near China’s southern border, where the first clusters of human cases would be expected.

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

Following the initial SARS outbreak, staff at labs studying the virus in Singapore, Taiwan, and China were inadvertently infected, including several at the Chinese National Institute of Virology in Beijing. Because of this history of mishaps, some scientists wonder why the WHO–China study team rated the possibility of a lab origin for COVID-19 as “extremely unlikely.”

“It’s reasonable to wonder why they’re dismissive,” said Marc Lipsitch, an epidemiologist at Harvard University, to BuzzFeed News.

The unusual features of the virus’s genetics and biology have been cited by supporters of the theory that it escaped from a lab.

During the SARS outbreak, scientists observed the virus rapidly mutating as it adapted to its new human hosts. SARS-CoV-2, on the other hand, appeared to be perfectly adapted to transmitting from one person to another.

In order for SARS-CoV-2 to enter human cells, the spike protein on its surface must bind to a receptor on the cells known as ACE2. After Chinese scientists published the virus’s first complete genetic sequence online in January 2020, a team led by Nikolai Petrovsky, an immunologist who works on vaccine development at Flinders University near Adelaide in Australia, began running computer simulations of how well the coronavirus spike protein could bind to ACE2 receptors from various species.

“What stumped us at the end of the project was that binding to human ACE2 was higher than binding to any other species we tested,” Petrovsky told BuzzFeed News. “That was very difficult for us to explain based on a natural origins theory.”

Other researchers concentrated on a part of the spike protein known as a “furin cleavage site,” which appears to be an important factor in SARS-ability CoV-2’s to infect human lung cells — speculating that this was deliberately inserted into the virus to study genetic changes that can make coronaviruses more dangerous to humans.

However, scientists led by Kristian Andersen of the Scripps Research Institute in La Jolla, California, concluded in March 2020 that the virus did not appear to have been genetically engineered. If that’s the case, they reasoned, you’d expect a familiar coronavirus backbone to be used in such experiments with a few key changes. However, SARS-CoV-2 has a diverse set of mutations that distinguish it from other coronaviruses.

Nonetheless, some scientists have speculated that SARS-CoV-2 was created to study the changes that could transform a naturally occurring coronavirus into a pandemic threat. Such “gain-of-function” research has long been fraught with controversy due to the dangers it may pose.

Because of her previous gain-of-function work, Shi of the Wuhan Institute of Virology, Daszak’s longtime research collaborator, was suspected. In 2015, she and Ralph Baric, a virologist at the University of North Carolina, Chapel Hill, published controversial findings in which they spliced the spike protein from a SARS-like bat coronavirus into another coronavirus that had previously been adapted to infect mice to investigate the possibility of cross-species transmission that could lead to a pandemic.

Before Trump and Pompeo got involved, the lab origin theory was already a political minefield. Things became even more complicated in the fall of 2020, when Yan Limeng, a scientist who had fled to the United States from Hong Kong, joined forces with a group linked to former Trump strategist Steve Bannon. Yan published two papers in which he made the explosive claim that SARS-CoV-2 was a bioweapon engineered and deliberately released by the People’s Liberation Army.

Experts unanimously agree that this is a bizarre conspiracy theory. Many virologists are also skeptical that SARS-CoV-2 was created 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 are still unsure how specific furin cleavage sites can make viruses more dangerous. “I just don’t think any human being could figure that out,” she said.

However, as the political temperature has cooled in the aftermath of Trump’s election defeat, some scientists have begun to openly discuss the lab accident theory. “[I]f SARS-CoV-2 escaped from a lab to cause the pandemic, understanding the chain of events and preventing this from happening again will become critical,” wrote David Relman, a microbiologist at Stanford University, in an opinion piece published on Election Day in PNAS, the journal of the National Academy of Sciences.

Shi did not respond to BuzzFeed News’ requests for an interview. However, the Baric experiment was carried out in North Carolina, not Wuhan. Shi flatly denied running any similar experiments since then in emailed responses to questions from Science magazine in July 2020.

However, a lab accident does not have to involve genetic engineering. Shi’s team has collected thousands of bat samples from all over China. To rule out the possibility that COVID-19 arose when a virus escaped from the lab, the Wuhan institute would have to open up all of its virus records and the audit it performed to see if any of them were a close match to SARS-CoV-2.

That was not permitted by the Chinese government. To add to the sense of secrecy, an online database containing information on the institute’s genetic sequences and samples appears to have gone dark in September 2019 and has not been reopened to the public since.

During their visit to the Wuhan institute, members of the WHO–China study team inquired about the database and virus sample audit. They were informed that the database had been removed following multiple hacking attempts.

“Their responses can then be examined and dissected. And that is exactly what Daszak did. “There is absolutely no evidence of a lab leak. I haven’t seen it yet, but I’m looking for it.”

Theory 4: The virus was spread via frozen food.

When the WHO–China team’s leaders announced their preliminary findings in a press conference on Feb. 9, many scientists were surprised that they were taking this theory seriously. For months, Chinese authorities have controversially linked new COVID-19 outbreaks in the country to imported frozen seafood. It appeared to be a story designed to promote the idea that the disease first appeared in another country.

“We know that the virus can persist and survive in these cold and frozen environments, but we don’t really know if the virus can then transmit to humans,” Embarek, the WHO food scientist who led the WHO–China team, said at a press conference in February. “As a result, much more research is required to better understand these intriguing pathways.”

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

“That is what we believe to be a very, very valid option,” Koopmans said.

Many virologists believe that COVID-19 originated in frozen food, in part because studies of virus transmission from surfaces or objects — known as “fomites” — show that it is inefficient compared to transmission through the air.

“The bottom line is that fomite transmission can occur, but it is extremely rare,” said Angela Rasmussen, a virologist at Columbia University.

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

More than a year into the pandemic, and with the most significant effort to determine its cause having yielded an open verdict, speculation of a lab origin will continue. However, continued demands for further investigation of that possibility are likely to cause Chinese authorities to obstruct 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 proponents of that theory make it even less likely that the Chinese government would ever consent to that type of investigation,” Rasmussen said.

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

After welcoming an international team of experts, China will most likely argue that other countries should do the same.A statement from the US State Department has been added to this story.

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WHO Report Leaves Big Questions About COVID-19 Origins