The story so far: A paper in Science Magazine, published on July 26, contained a post- facto analysis that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China and established the Huanan market in Wuhan as the epicentre of the pandemic. While this is unlikely to seal forever the controversial debate over two years, including counter theories of a lab leak that led to the virus causing havoc in the world, it brings the issue to the first-of-its-kind empirical evidence-based averment and declaration on the origin of the SARS-CoV-2 virus. It is important to produce and examine the evidence on this account, as understanding how the virus emerged is perceived as essential to preventing further outbreaks of zoonotic diseases.
What does the Science paper show?
During the early stages of the COVID-19 pandemic, the dominant hypothesis was that animals sold at the Huanan market were the likely source of the unexplained pneumonia cases. This led to the closure of the Huanan market on January 1, 2020.
The paper underlines the original theory that the “earliest known COVID-19 cases from December 2019, were geographically centered on this market.” It shows that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019. The analysis indicated a clear and present link between the market and the emergence and spread of the deadly virus.
The authors record: Of the initial 41 people hospitalised with unknown pneumonia by January 2, 2020, 66% had direct exposure to the Huanan Wholesale Seafood Market. These first cases were confirmed to be infected with a novel coronavirus, subsequently named SARS-CoV-2, and were suffering from a disease later called COVID-19. These early reports were free from ascertainment bias as they were based on signs and symptoms before the Huanan market was identified as a shared risk factor.
A systematic review of all cases notified to China’s National Notifiable Disease Reporting System by hospitals in Wuhan showed that 55 of 168 of the earliest known COVID-19 cases were associated with this market. However, this alone could not indicate that the pandemic started there.
What methodology did the authors use?
The authors, comprising researchers from across the world, ‘obtained data from a range of sources to test the hypothesis that the COVID-19 pandemic began at the Huanan market.’ Michael Worobey et al say: “We were able to reliably extract the latitude and longitude coordinates of 155 cases from maps in the 2021 WHO mission report.”
While early COVID-19 cases occurred across Wuhan, the majority clustered in central Wuhan near the west bank of the Yangtze River, with a high density of cases near to, and surrounding, the Huanan market. In a kernel density estimate (KDE) using the 120 cases with no known linkage to the market, the market remains within the highest density 1% contour. Using a COVID-19 assistance app on Sina Weibo, the researchers discovered that unlike early COVID-19 cases, by January and February, many of the sick who sought help resided in highly populated areas of the city, and particularly in areas with a high density of older people.
The authors considered three categories of cases, and they were all significantly closer to the Huanan market than expected — all cases, cases linked directly to the Huanan market and cases with no evidence of a direct link to the Huanan market. They also performed a spatial relative risk analysis to compare December 2019 COVID-19 cases with January-February 2020 cases, reported via Weibo. The Huanan market is located within a well-defined area with high case density. No other regions in Wuhan showed a comparable case density, they reported.
A report in a recent preprint, stated that only lineage B (of the two identified, A and B) sequences had been sampled at the Huanan market. Eleven lineage B cases from December 2019 resided closer than expected to the Huanan market. The authors went on to show that both identified lineage A cases had a geographical connection to the market, supporting the assumption that the virus was spreading outwards of the Huanan market.
They reported that multiple plausible intermediate wildlife hosts of SARS-CoV-2 progenitor viruses, including red foxes, hog badgers and common raccoon dogs, were sold live at the Huanan market up until at least November of 2019. The authors “reconstructed the floor plan of the market and integrated information from business registries of vendors at the market as well as an official report recording fines to three business owners for illegal sale of live mammals. From this, we identified an additional five stalls that were likely selling live or freshly butchered mammals or other unspecified meat products in the southwest corner of the western section of the market.” With further analyses, they discovered that the region of increased positive sample density in the southwest corner of the western section of the market remained consistent.
What were the limitations to the study?
Clearly, “events upstream of the market, as well as exact circumstances at the market, remain obscure, highlighting the need for further studies to understand and lower the risk of future pandemics.”
In a post-facto analysis, not having access to the precise latitude and longitude coordinates of all these cases, lacking direct evidence of an intermediate animal infected with a SARS-CoV progenitor virus, and the lack of a line list of early COVID-19 cases are acknowledged as drawbacks.
The authors have called for maximum effort to elucidate the upstream events that might have brought SARS-CoV-2 into the Huanan market, culminating in the COVID-19 pandemic. “To reduce the risk of future pandemics we must understand, and then limit, the routes and opportunities for virus spillover,” the authors concluded.
