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New research: Two studies reinforce Covid-19’s Wuhan market origin

Two companion papers published in Science magazine on July 26 indicate that the Covid-19 pandemic “most likely began with at least two separate zoonotic transmissions starting in November 2019”, and that SARS-CoV-2 emerged via the live wildlife trade in China, with the Huanan Seafood Wholesale Market in Wuhan being the likely early epicenter of the pandemic.

The two studies — which were first released online on February 26 this year but were since awaiting peer review — confirmed the initial understanding of the beginnings of the pandemic, which, however, became controversial in the months after the outbreak.

The lead authors of both studies are affiliated to American universities — the University of Arizona and the University of California San Diego — and the research has been primarily funded by the United States National Institutes of Health (NIH). One of the papers also received funding from the Centers for Disease Control and Prevention (CDC), the US national public health agency.

The paper titled ‘The Huanan Seafood Wholesale Market in Wuhan was the early epicenter of the COVID-19 pandemic’ (Worobey et al.), mapped geo locations of 155 of the initial 174 cases, and found that the clustering in December around the Huanan market contrasts with the pattern of widely dispersed cases across Wuhan by early January through mid-February 2020 — indicating that the cases flowed outward from the market to elsewhere.

The second paper, ‘The molecular epidemiology of multiple zoonotic origins of SARS-CoV-2’ (Pekar et al.), through simulations of SARS-CoV-2-like epidemics combined with genomic sequence data, concludes that “as with other coronaviruses , SARS-CoV-2’s emergence likely resulted from multiple zoonotic events” (the spread of germs from animals to humans).

Related findings

The molecular epidemiology paper argues that the paradox of genomic diversity in the early days (before February 2020) is best explained by rejecting a single-introduction origin of the pandemic from one lineage, and instead considering that “at least 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,” occurred.

The companion paper on the Huanan market epicenter notes that “plausible intermediate wildlife hosts of SARS-CoV-2 progenitor viruses, including red foxes, hog badgers and common raccoon dogs, were sold live at the…market up until at least November of 2019” . Through spatial analyzes within the market, the research records that “SARS-CoV-2-positive environmental samples, including cages, carts, and freezers, were associated with activities concentrated in the southwest corner of the market” — the same section where live mammals , including raccoon dogs, hog badgers, and red foxes, were being sold immediately prior to the outbreak of the epidemic.

The study took “multiple positive samples” from a stall known to have sold live mammals, and from a water drain close by, suggesting that infected animals were present at the market at the beginning of the outbreak.

The molecular epidemiology paper says that lineage B was introduced into humans prior to lineage A — and lineage B was introduced “no earlier than late-October and likely in mid-November 2019, and the introduction of lineage A occurred within days to weeks of this event.” Also, “there were likely multiple failed introductions of SARS-CoV-2”, which means that the virus could have been in circulation in the human population without being noticed. The researchers estimate that “eight introductions led to the establishment of both lineage A and B in humans”.

The Huanan market epicenter paper records that the center point of the 11 lineage B cases was 1.95 km from the market, and the two A lineage cases for which information location was available were both reportedly residing nearby. It deduces that it is likely that “during the early epidemic lineage A was, like lineage B, disseminating outward from the…market into the surrounding neighbourhoods.”

Unanswered questions

The Huanan market paper acknowledges that a crucial question that remains unanswered is the events upstream of the market — that is, prior to the transmission from the market. The exact circumstances at the market too remain obscure, and direct evidence of an intermediate animal infected with SARS-CoV-2 either at the market or at a location connected with the supply chain, remains missing.

The authors acknowledge that precise latitude and longitude coordinates of all cases were not available, with many such cases missing the date of onset of symptoms as well. Of the 174 Covid-19 cases in Hubei province in December 2019, geolocations of 155 cases could be reliably extracted.

One of the papers hypothesizes that the possible source of introduction of lineage B was a seafood vendor at the market, even though there is no published genomic data from the sample of this patient. The assumption is based on the fact that an environmental sample from the stall this vendor operated was detected with lineage B.

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