Conspiracy theorists need little more than suspicion, some cherry-picked facts and vivid imagination to spin stories about the origins of the covid-19 pandemic. But for researchers working to establish facts, the path to truth is much more painful.
Their search will take them through a variety of medical records whose detailed details will be important guides to the timing and circumstances of the coronavirus’ birth as a human pathogen. Patients’ recall of their whereabouts and contacts will also be important.
But even if the Chinese government was willing to open all its patient records to international investigators – it is not at present – symptom reports and patient memories can be erroneous and confusing. Researchers must check every fact as they illuminate history, piece by piece.
University of Arizona evolutionary biologist Michael Worobey offers a down payment on such a search in this week’s issue of the journal Science. Taken from medical journals, the work of WHO investigators, media reports and online accounts, Worobey’s Reconstruction leaves many questions unanswered. But it provides a roadmap for further investigation.
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Worobey has played an influential role. He was one of 18 researchers whose objections to a WHO report on the origin of the coronavirus resumed the investigation into the possibility that it may have leaked from the Wuhan Institute of Virology.
Their mail was published in Science after WHO stated that it is “probably very likely” that the virus jumped to humans from animals, and “extremely unlikely” that it escaped from the government laboratory. The group noted that the two theories “were not considered in balance”, called for “a proper investigation” to solve the problem.
Worobey said then that “both” explanations “remain on the table for me.” But his new work leans a lot towards the explanation of “animal waste”.
Worobey’s efforts meet mixed reviews.
“I do not think this promotes our collective understanding of what really happened in a significant way,” he said Dr. David Relman, Stanford’s microbiologist who organized Science Letter. Because Worobey’s new story is constructed primarily of “third- and fourth-hand information,” it is fragmentary, inconsistent, and potentially unreliable, Relman said.
But Scripps Institution microbiologist Kristian Andersen, which has long argued that an animal spill was more likely than a lab leak, praised Worobey’s research for “revealing several new key insights.”
The evidence gathered “clearly points to the Huanan market as a very likely source of the origin of the covid-19 pandemic,” Andersen said.
Worobey’s account questions the date and location of the earliest reported case of the mysterious type of pneumonia that was later recognized as COVID-19. His research suggests that it was not – as has been widely reported – a 41-year-old accountant with no connection to Huanan Market, but a seafood seller who worked there. (A Chinese investigative reporter would discover that the auditor’s fever on December 8 was due to an infection after dental surgery to remove retained baby teeth. The auditor would continue to develop another fever eight days later, which was a sign of covid-19.)
As many as 11 days before Chinese authorities focused their attention on the Huanan market as the usual link in the mysterious infections, doctors at two hospitals in Wuhan had already identified 14 cases of the unexplained pneumonia. Eight of these patients had spent time in the market selling live raccoon dogs, a species known to carry SARS-like coronavirus.
The significance of such small details would not be obvious to temporary supporters of the original debate. But they mean a lot.
Those who claim that China has covered up an unintentional laboratory leak or deliberate release of a engineered pathogen have taken up this finding in the WHO report: Only 33% of 168 patients who developed the unexplained pneumonia early in the outbreak had a direct link to Huanan market . They add that even that number has probably increased by doctors who were looking for links to the market after Chinese authorities designated the site as the likely source.
They have also made much of the now-disputed report that the earliest known patient (the 41-year-old accountant) lived nearly 200 miles south of Huanan Market and had never been there, but he appeared ill at a hospital near the Wuhan Institute of Virology.
Dr. Marc Suchard, a UCLA researcher who uses genetic sequences to study the spread of disease, said Worobey’s reconstruction clarifies that “most early cases occur near the market, identifying it as an early epicenter.” Suchard said he expects to work with Worobey in the next phase of this research.
China insists that the SARS-CoV-2 virus originated from a proliferation event. Authorities there said they responded quickly to reports of an unexplained disease in Wuhan, quickly traced it to the Huanan market and activated a national warning system.
They dismiss the possibility that the virus escaped from the virology lab in Wuhan. But they have been reluctant to share their information with WHO investigators. And because the government has covered up mistakes in previous disasters, skepticism about its claims has been widespread.
Worobey did not acknowledge the politically charged debate about the origin of the virus. But he made it clear that his reconstruction of events points strongly to a spillover declaration.
For example, according to his report, 10 of the 19 earliest identified cases – 53% – had a link to the market. That number could not have been increased by doctors who followed the government’s leadership, he said, because they were all identified before the authorities made any announcement.
“There was a genuine predominance of early cases of covid-19 associated with Huanan Market,” Worobey wrote.
He also wrote that, given what is now known about the SARS-CoV-2 virus, it should come as no surprise that many of the early patients had no connection to the Huanan market. The virus is easily spread by people with few or no symptoms. It takes almost two weeks for an infection to develop into a serious illness, and no more than 7% of those infected end up in hospital.
This means that when people started landing at Wuhan’s hospital, the virus had probably been circulating locally for weeks – and at least 93% of those infected were out and about and could spread it in a city of 11 million.
Among patients without a direct connection to the market, most lived nearby. It “is remarkable and provides convincing evidence that Community transfer started in the market,” Worobey wrote.
These facts also suggest that the “patient zero” of the pandemic will probably never be found.
Sometime in late November or early December, that person may have had lunch next to infected raccoon dogs in their cages at Huanan Market. He or she may have been one of the nearly 50% of people who do not feel particularly ill but who are still quite effective at passing on SARS-CoV-2.
The animal that incubated the virus is even less likely to be found. Chinese researchers told WHO investigators took samples from 188 animals from 18 species on the market, and all tested negative. And since the market was closed and disinfected on January 1, 2020, there is no way to look any further.
So researchers must continue to collect epidemiological data and sort through the telling details to create as complete a picture as possible of the virus’ birth.
Genetic sequencing data can also help, Worobey said. When the virus moves from person to person, its genetic signature changes just enough to reveal the order in which infections occurred. When epidemiologists and geneticists combine their data, they are better able to create a family tree of infections.
When cross-checking genetic signatures with patients ‘accounts of their contacts and whereabouts, they may be able to time-stamp certain infections and discern the spatial patterns of the virus’ earliest transmissions. It should get them closer to the root of the family tree – maybe not patient zero, but close.
“Complete evidence that a Huanan Market origin comes from infected wildlife may still be available,” Worobey wrote. “Preventing future pandemics depends on this effort.”