Where Did Covid Come From?

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News in focus (Close relatives of SARS-CoV-2 have been found in bats and pangolins in southern China.) Some of the samples tested positive for antibodies against SARS-CoV-2, but Ian Lipkin, an infectious-diseases researcher at Columbia University in New York City, who worked on the analysis, says the test was not specific enough to say for sure that the antibodies weren’t caused by infection with other viruses. “There is a lot of laboratory work that needs to be done,” says Lipkin, who also wants to know whether there are autopsy samples from before December 2019 that could be studied for traces of viral genetic material.

Was the virus spreading in people outside China before December 2019? Answering this question is also key to estab- lishing the timeline of the first COVID-19 cases. Previously, researchers in Europe 1,2,3 have reported finding antibodies against RETEMAL/AFP/GETTY HECTOR WHO investigators visit sites in China as part of their probe into the pandemic’s origins. SARS‑CoV-2 in samples taken at blood banks from November 2019 onwards. Ben Embarek says this doesn’t necessarily suggest that the virus originated in Europe, WHERE DID COVID COME but that it does support the idea that the virus was spreading in Wuhan before the first known FROM? FIVE MYSTERIES cases. “Wuhan at that time was a very well-con- nected international city with direct flights to THAT REMAIN the entire planet on a daily basis. So if it was circulating in Wuhan, it could easily have been In the wake of a World Health Organization brought to other parts of the world through travellers, and circulating again, undetected, investigation, scientists still have questions. in different regions,” he says. Still, he recommends that the blood samples By Smriti Mallapaty Yet evidence of earlier spread has proved from Europe be retested to confirm that they elusive. Researchers in China conducted an indicate cases of COVID-19. Some of them are ollowing a month-long fact-finding mis- extensive survey of patient reports from hos- already being reanalysed, he says. sion in China, a World Health Organi- pitals in Wuhan made between October and zation (WHO) team investigating the December 2019, and identified fewer than What was the role of the Huanan origins of the COVID-19 pandemic 100 people who had symptoms of COVID‑19. Seafood Market? concluded that the virus probably orig- They tested the blood of 67 of those people for The intermediate animal that passed the virus Finated in bats and passed to people through antibodies generated by past infection with from bats to people has not been identified, an intermediate animal. But fundamental SARS-CoV-2, but found none. This suggests but researchers think it might be a wild species questions remain about when, where and there wasn’t a large cluster of infections before that is sold as food in ‘wet markets’, which typ- how SARS-CoV-2 first infected people. As the December, or an unusual spike in deaths in the ically sell live animals. Early in the pandemic, international team finalizes a report on its surrounding province of Hubei. investigators homed in on the Huanan Seafood findings, Nature speaks to four of the inves- But Ben Embarek says the analysis should Market in Wuhan, because it sold fresh and fro- tigators about what they still want to know. be repeated using less restrictive symptom zen animals and many of the earliest reported criteria, to make sure that researchers spot infections were in people who had visited it. Was the virus circulating in Wuhan all potential COVID-19 cases. But the lead went cold when other early cases before the first known cases? Scientists in China should also search for were found that were not associated with the To trace the virus’s origin, it’s crucial to pin evidence of past infection in some 200,000 market. Viral material was identified in drains down exactly when the first cases occurred archived samples currently held at the Wuhan and sewage at the market, but none was found in people. The WHO team established that the Blood Center and in other regions, says team on any animal carcasses. first person known to have COVID-19 was an member Dominic Dwyer, a medical virolo- Still, the market is the only place where a office worker in Wuhan, China, with no recent gist at New South Wales Health Pathology in large number of the people infected at the travel history, who began showing symptoms Sydney, Australia. This would show whether start of the outbreak were exposed to meat and on 8 December 2019, says Peter Ben Embarek, the virus was spreading in the general popu- animals. It’s important to establish how the a food-safety scientist at the WHO in Geneva, lation in China before December 2019. virus got into the market and whether it was Switzerland, who led the investigation. But Some scientists not involved in the WHO on an animal, says WHO team member Hung the virus was probably spreading in the city investigation have already looked at blood- Nguyen-Viet, an environment and food-safety before that, because it was well established bank samples taken up to a year before the researcher at the International Livestock by later that month, he says. pandemic, in Guangzhou, southern China. Research Institute in Nairobi.

Nguyen-Viet says the team identified ten stalls selling wildlife, either wild or farmed, Q&A that could have carried the virus into the market from farms in southern China. Some wild animals sold for meat, such as rabbits and ferret-badgers, are susceptible to SARS-CoV-2. Deducing which pandemic WHO team member Peter Daszak, president

EUGENIE SOPHIE EUGENIE of the non-profit research organization Eco- policies work best health Alliance in New York City, says that the farms should be investigated to see whether Since the start of the COVID-19 pandemic, were among the most effective policies there were infections in the animals or among thousands of scientists and volunteers (N. Haug et al. Nature Human Behav. 4, workers. When the team interviewed the first have been tracking the interventions 1303–1312; 2020). person known to have COVID-19, he mentioned that governments have adopted to curb But there is less agreement, when that his parents had visited a local community viral spread — from closing restaurants analysing different trackers, on how to wet market, says Daszak. to mandating face masks. They hope to rank these measures. For example, it is not deduce which policies are most effective. certain that highly restrictive measures are Did frozen wild-animal meat have a At a conference this month, scientists automatically more effective than a smart role in the early spread of the virus? involved in 50 tracking databases mix of comparatively modest restrictions The WHO team concluded that it’s most likely discussed their efforts. Peter Klimek, a implemented with better timing. the virus jumped from live animals to people, mathematical physicist at the Complexity but Ben Embarek says it is possible that the Science Hub (CSH) Vienna and the Medical Why is it hard to estimate the effects of virus entered the Huanan market through University of Vienna, who is involved in interventions? infected frozen wild animals from farms in the CSH’s tracking project, explains the It is difficult to untangle the effects of any southern China, and then sparked an outbreak. challenge. given measure from those of other policy Although researchers in China have isolated interventions. There are many statistical viral RNA from the packaging of imported fro- How much work has gone into these approaches to disentangling relationships zen fish4, Ben Embarek says the WHO team trackers? in complex systems, but none of them is concluded that these goods were not likely to In our tracker, more than 40 volunteers and perfect. And sociocultural factors can make be the route of the virus’s first arrival in Wuhan. scientists have been involved in assigning social distancing more effective in one Lipkin says there is no evidence that the codes to more than 11,000 measures in country than in another. virus entered the market through infected 57 countries. Other efforts, such as the The effects of interventions also change frozen wild animals. It could have just as easily CoronaNet consortium and the government over time. The situation has become more been brought in by infected people who had response tracker run by the University complicated as government interventions handled wild animals, he says. of Oxford, UK, each have hundreds of have become more diverse, and as people volunteers and researchers. Some tracking adhere less willingly to restrictions. Was the virus circulating in animals efforts have received funding, but most are in China before the pandemic? struggling owing to a lack of money, and Why not combine the trackers? To establish which animal passed the virus to some have had to stop. It’s also a challenge Each tracker has its own perspectives. Some people, researchers need to find evidence of to keep volunteers motivated. do integrate data from different databases, the virus in that species. Researchers in China including one maintained by the World tested some 30,000 wild, farmed and domes- How have the trackers been used? Health Organization. But this comes at the tic animals in 2019 and 2020 but found no evi- We advise the Austrian government on expense of some of the granularity that dence of active or past SARS-CoV-2 infection, policy measures to contain the spread the original databases might have had. except in some cats in Wuhan in March 20205. of coronavirus and avoid health-system From the perspective of data quality and However, Ben Embarek says that these sur- overload. When we’re asked questions, such reproducibility of results, merging trackers veys were not representative of China’s overall as why some countries have much lower into a super-database isn’t a good idea. animal population, and that many more ani- case numbers than others, the first places we mals need to be tested for traces of infection, look are the databases tracking government How might this sort of work change particularly on wildlife farms. “The amount interventions. We still don’t know what is the in the future? of testing that’s been done is not sufficient to best way to plug the data from the tracking There is growing societal and political say, in any way, that wildlife farms were not systems into mathematical models. But the pressure to understand hypothetical carrying the virus,” says Daszak. trackers are a unique treasure trove that we scenarios: how not having implemented The explosive way in which the outbreak can use to make epidemiological modelling a certain measure might have changed took off in Wuhan in December suggests a data-driven science and to prepare for the the course of the pandemic. For example, that the virus was probably introduced once, next pandemic. was it really necessary to close schools? through the wildlife trade, says Daszak. He Or will the social and economic costs turn says future testing should focus on farmed What have they told us so far? out to have outweighed the health-related wild animals. When many countries applied various benefits? Without reliable tracker data, control measures simultaneously, we there will be no solid evidence to answer 1. Carrat, F. et al. Eur. J. Epidemiol. https://doi.org/10.1007/ knew very little about the effects of such questions. s10654-020-00716-2 (2021). 2. Amendola, A. et al. Emerg. Infect. Dis. 27, 648–650 (2021). government interventions. When more data 3. Apolone, G. et al. Tumori J. https://doi. became available, we found that curfews, Interview by Quirin Schiermeier org/10.1177/0300891620974755 (2020). cancellations of small gatherings, and This interview has been edited for length and 4. Liu, P. et al. Biosaf. Health 2, 199–201 (2020). 5. Zhang, Q. et al. Emerg. Microbes. Infect. 9, 2013–2019 closures of schools, shops and restaurants clarity. (2020).