Studies point to Huanan market as epicenter of SARS-CoV-2 emergence, from activities associated with wildlife trade

Two studies published in Science by Michael Worobey et al. and Jonathan Pekar et al. use complementary approaches – involving spatial and environmental analyses, as well as molecular analyses – to provide evidence that the Huanan market in Wuhan, China, was the early epicenter for the COVID-19 pandemic. The scientists concluded that SARS-CoV-2 was very likely present in live mammals sold at this market in late 2019 and suggest the virus spilled over into people working or shopping there from two separate zoonotic transmissions, in which lineage A and B progenitor viruses were both circulating in non-human mammals prior to their introduction into humans. Future work, say the authors of both studies, should be focused on better understanding events upstream of the introduction of SARS-CoV-2 to the market, including where the wild mammals for sale at Huanan came from, to lower the risk of future pandemics.

Despite the observation that the preponderance of earliest known COVID-19 cases – flagged by hospitals in Wuhan in December 2019 – were linked to the Huanan market, this did not establish activities at the Huanan market as the trigger for the pandemic. But, as Worobey and colleagues note, determining the epicenter of the COVID-19 pandemic at the neighborhood- rather than city-level could help resolve if SARS-CoV-2 had a zoonotic origin. To test the hypothesis of the market as the pandemic’s epicenter, Worobey et al. obtained data from a range of sources. First, they used mapping tools to estimate the longitude and latitude locations of more than 150 of the earliest reported virus cases from December 2019, including those without reported direct links to the market. The highest density of these cases centered around the Huanan market, they say. By mapping cases from January and February of 2020 using data from Weibo, a social media app that created a channel for people with Covid to seek medical help, the researchers identified cases in other parts of central Wuhan radiating from the market as the pandemic progressed. Using social media "check-in" data, the researchers performed analyses to rule out the many other locations in Wuhan, a city of 11 million, that would have been equally or more likely than the market to sustain the first cluster of a new respiratory pathogen. In further analyses, they report that multiple plausible intermediate wildlife hosts of SARS-CoV-2 progenitor viruses were sold live at the Huanan market until at least November of 2019. Using and extending a data set on samples from surfaces in the Huanan market, they identified five stalls that were likely selling live or freshly butchered mammals; the proximity to such live mammal vendors was predictive of human virus cases, their analyses show.

To further understand the circumstances that led to the pandemic's origin, Pekar and colleagues analyzed the genomic diversity of SARS-CoV-2 early in the pandemic. While the diversity of SARS-CoV-2 increased as the pandemic spread from China to other countries, two lineages of SARS-CoV-2 – designated A and B – marked the beginning of the COVID-19 pandemic in Wuhan. Only lineage B was represented in the eleven sequenced genomes from humans directly associated with the Huanan market. The earliest lineage A genomes from humans lacked any known contact to the market but were sampled from humans who lived or stayed close by. It has been hypothesized that the two lineages emerged separately. To test this hypothesis, Pekar and colleagues analyzed genomic and epidemiological data from early in the COVID-19 pandemic with models and simulations. Through their analyses, they provide support for two separate introductions of lineages A and B into humans, both circulating in non-human mammals prior, with lineage B first appearing in humans no earlier than late October 2019 and likely in mid-November 2019 and lineage A being introduced within days to weeks of this event. Their simulations do not support a single introduction of the virus giving rise to the observed patterns of virus lineage spread. Further, the results from the study of Worobey et al., they say, are consistent with the idea of a separate and subsequent origin of lineage A at the Huanan market in late-November 2019. These findings, say the authors, indicate that it is unlikely that SARS-CoV-2 circulated widely in humans prior to November 2019 and define the narrow window between when SARS-CoV-2 first jumped into humans and when the first cases of COVID-19 were reported. The authors report several limitations to their studies, in both cases.

***A related news briefing was held as a Zoom Webinar on 26 June 2022, at 2:00 p.m. U.S. ET. Recordings of the briefing can be found here.