Challenges over attempts to conduct crucial studies in China have led to the World Health Organisation (WHO) abandoning the second phase of its scientific investigation into the origins of the Covid-19 pandemic, reports Nature.
Researchers are disappointed that the investigation is not going ahead, because understanding how the coronavirus SARS-CoV-2 first infected people is important for preventing future outbreaks. But without access to China, there is little the WHO can do to advance the studies, says Angela Rasmussen, a virologist at the University of Saskatchewan in Canada. “Their hands are really tied.”
In January 2021, an international team of experts convened by the WHO travelled to Wuhan, where the virus that causes Covid-19 was first detected. With Chinese researchers, they reviewed evidence on when and how the virus might have emerged, as part of phase one.
The team released a report in March that year outlining four possible scenarios, the most likely being that SARS-CoV-2 spread from bats to people, possibly through an intermediate species. Phase one was designed to lay the groundwork for a second phase of in-depth studies to pin down exactly what happened in China and elsewhere.
But two years since that high-profile trip, the WHO has abandoned its phase two plans. “There is no phase two,” Maria Van Kerkhove, an epidemiologist at the WHO in Geneva, Switzerland, told Nature. The WHO planned for work to be done in phases, she said, but “that plan has changed”. “The politics of this across the world hampered progress on understanding the origins,” she said.
Researchers are undertaking some work to pin down a timeline of the virus’ initial spread. This includes efforts to trap bats in regions bordering China in search of viruses closely related to SARS-CoV-2; experimental studies to help narrow down which animals are susceptible to the virus and could be hosts; and testing of archived wastewater and blood samples collected around the world in late 2019 and early 2020.
But researchers say that too much time has passed to gather some of the data needed to pinpoint where the virus originated.
Tense times
Many researchers are not surprised the WHO’s plans have been thwarted. In early 2020, members of then-US President Donald Trump’s administration made unsubstantiated claims that the virus had originated in a Chinese laboratory, and US intelligence officials later said they had begun investigations. The Wuhan Institute of Virology is a high-security lab that works on coronaviruses: Chinese officials had questioned whether the virus originated inside the country’s borders.
Amid simmering hostility between the two superpowers, WHO member states requested in May 2020 that the agency put together a science-led effort to identify how the pandemic started. Although China agreed to the mission, tensions were high by the time the WHO group left for Wuhan, and engagement with China quickly unravelled after they returned.
In its March 2021 report, the team concluded that it was “extremely unlikely” that the virus had accidentally escaped from a laboratory. But the inclusion of the lab-incident scenario in the final report was a key point of contention for Chinese researchers and officials, says Dominic Dwyer, a virologist at New South Wales Health Pathology in Sydney, who was a member of the WHO team.
That July, the WHO sent a circular to member states outlining how it planned to advance origins studies. Proposed steps included assessing wild-animal markets in and around Wuhan and the farms that supplied those markets, as well as audits of labs in the area where the first cases were identified.
However, Chinese officials rejected the WHO’s plans, taking particular issue with the proposal to investigate lab breaches. Zhao Lijian, spokesperson for China’s Foreign Ministry, said the WHO proposal was not agreed by all member states, and that the second phase should not focus on pathways the mission report had already deemed extremely unlikely.
In August 2021, members of the original mission team published a comment piece in Nature urging quick action on the proposed studies to trace the virus’ origins. “We wrote that piece because we were worried phase two might not happen,” said Marion Koopmans, a virologist at Erasmus University Medical Centre in Rotterdam, the Netherlands, and a member of the mission to Wuhan. “I’m sorry to say that that’s indeed what panned out.”
Stalled work
Gerald Keusch, associate director of the National Emerging Infectious Diseases Laboratory Institute at Boston University in Massachusetts, says the origins investigation was “poorly handled by the global community. It was poorly handled by China. It was poorly handled by the WHO.” The WHO should have been relentless in creating a positive working relationship with the Chinese authorities, says Keusch; if it were being stonewalled, it should have been honest about that.
Van Kerkhove says that the WHO’s director-general, Tedros Adhanom Ghebreyesus, has continued to engage directly with the Chinese Government officials to encourage more open communication and to share data. And WHO staff have reached out to the China Centre for Disease Control and Prevention in Beijing to try to establish collaborations. “We really want to be able to work with our colleagues there,” says Van Kerkhove. “It’s a deep frustration.”
The Chinese Ministry of Foreign Affairs did not respond to Nature’s requests for comment on why the phase-two studies have stalled.
In November 2021, the WHO formed the Scientific Advisory Group for the Origins of Novel Pathogens (SAGO) – a permanent team of experts who have since written a proposal for how to conduct origins studies for future outbreaks. SAGO has also evaluated evidence on the origins of SARS-CoV-2.
Blood-donors study
Outside the formal WHO-led process, some studies proposed for phase two have gone ahead. In May last year, researchers in Beijing and Wuhan published the results of an analysis of donor blood supplied to the Wuhan Blood Centre before December 2019.
The researchers were looking for SARS-CoV-2 antibodies that could signify some of the earliest infections in the pandemic. The team screened more than 88 000 plasma samples collected between 1 September and 31 December 2019, but did not find any SARS-CoV-2-blocking antibodies in the samples.
Michael Worobey, an evolutionary virologist at the University of Arizona in Tucson, says the work is an important contribution from Chinese scientists, supporting earlier genomic analyses showing that the virus probably had not emerged as early as September and was not widespread in Wuhan in late 2019.
Another study by researchers from China, which has not been peer reviewed, reported finding traces of SARS-CoV-2 in January and February 2020 at the Huanan seafood market in Wuhan, which was visited by many of the earliest known people with Covid-19.
Samples were taken from sewage, drains, the surfaces of doors and market stalls, and the ground, among other places.
The researchers concluded that the virus was probably shed by humans, but Rasmussen and others are keen to take a closer look at the raw data, which included swabs from a de-feathering machine, to see whether they can identify animal species.
“I still hope that progress will be made,” says Thea Fischer, a public-health virologist at the University of Copenhagen, who was a member of the mission to Wuhan and is part of SAGO.
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Nature Comment – Origins of SARS-CoV-2: window is closing for key scientific studies (Open access)
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