A study has revealed that the WHO advisory group suggested that the Huanan seafood market in Wuhan, China played an important role in the amplification of the pandemic, and investigations into it is recommended.

A group of researchers found how severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in 2019 is critical to preventing zoonotic outbreaks before they become the next pandemic. The Huanan Seafood Wholesale Market in Wuhan, China, was identified as a likely source of cases in early reports but later this conclusion became controversial. The research show the earliest known COVID-19 cases from December 2019, including those without reported direct links, were geographically centered on this market. We report that live SARS-CoV-2 susceptible mammals were sold at the market in late 2019 and, within the market, SARS-CoV-2-positive environmental samples were spatially associated with vendors selling live mammals. While there is insufficient evidence to define upstream events, and exact circumstances remain obscure, our analyses indicate that the emergence of SARS-CoV-2 occurred via the live wildlife trade in China, and show that the Huanan market was the epicenter of the COVID-19 pandemic.

The findings of the study were published in Science magazine.

On 31 December 2019, the Chinese government notified the World Health Organization (WHO) of an outbreak of severe pneumonia of unknown etiology in Wuhan, Hubei province, a city of approximately 11 million people. Of the initial 41 people hospitalized with unknown pneumonia by 2 January 2020, 27 (66%) had direct exposure to the Huanan Wholesale Seafood Market (hereafter, "Huanan market"). These first cases were confirmed to be infected with a novel coronavirus, subsequently named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and were suffering from a disease later named coronavirus disease 2019 (COVID-19). The initial diagnoses of COVID-19 were made in several hospitals independently between 18 and 29 December 2019.

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 subsequent systematic review of all cases notified to China's National Notifiable Disease Reporting System by hospitals in Wuhan as part of the joint WHO-Chinese "WHO-convened global study of origins of SARS-CoV-2: China Part" (hereafter, "WHO mission report") showed that 55 of 168 of the earliest known COVID-19 cases were associated with this market.

However, the observation that the preponderance of early cases were linked to the Huanan market does not establish that the pandemic originated there.

Sustained live mammal sales during 2019 occurred at the Huanan and three other markets in Wuhan, including wild and farmed wild-life. Several of these species are known to be experimentally susceptible to SARS-related coronaviruses (SARSr-CoVs), such as SARS-CoV (hereafter, "SARS-CoV-1") and SARS-CoV-2. During the early stages of the COVID-19 pandemic, animals sold at the Huanan market were hypothesized to be the source of the unexplained pneumonia cases (data S1), consistent with the emergence of SARS-CoV-1 from 2002-2004, as well as other viral zoonoses. This led to the decision to close and sanitize the Huanan market on 1 January 2020, with environmental samples also being collected from vendors' stalls (data S1).

Early cases lived near to and centered on the Huanan market

The 2021 WHO mission report identified 174 COVID-19 cases in Hubei province in December 2019 after careful examination of reported case histories. Although geographical coordinates of the residential locations of the 164 cases who lived within Wuhan were unavailable, we were able to reliably extract the latitude and longitude coordinates of 155 cases from maps in the report.

Both early lineages of SARS-CoV-2 were geographically associated with the market
Two lineages of SARS-CoV-2 designated A and B have co-circulated globally since early in the COVID-19 pandemic. Until a report in a recent preprint, only lineage B sequences had been sampled at the Huanan market. The eleven lineage B cases from December 2019, for which we have location information, resided closer than expected to the Huanan market compared to the age-matched Wuhan population distribution (median 8.30km; p=0.017). The center-point of the eleven lineage B cases was 1.95km from the Huanan market, also closer than expected (p=0.026). The two lineage A cases for which we have location information involved the two earliest lineage A genomes known to date. Neither case reported any contact to the Huanan market. The first case was detected before any knowledge of a possible association of unexplained pneumonia in Wuhan with the Huanan market and therefore could not have been a product of ascertainment bias in favor of cases residing near the market. The second had stayed in a hotel near the market for the five days preceding symptom onset. Relative to the age-matched Wuhan population distribution, the first individual resided closer to the Huanan market (2.31km) than expected (p=0.034). While the exact location of the hotel near the market was not reported, there are at least 20 hotels within 500 m (table S1). Under the conservative assumption that the hotel could have been located as far as 2.31km from the Huanan market (as was the residence of the other lineage A case), and assuming this location is comparable to a residential location given the timing of the stay prior to symptom onset, it would be unlikely to observe both the earliest lineage A cases this near to the Huanan market (p=0.001 or less). That both identified lineage A cases had a geographical connection to the market, in combination with the detection of lineage A within the market, support the likelihood that during the early epidemic lineage A was, like lineage B, disseminating outward from the Huanan market into the surrounding neighborhoods.

Wild animal trading in Wuhan markets
In addition to selling seafood, poultry, and other commodities, the Huanan market was among four markets in Wuhan reported to consistently sell a variety of live, wild-captured or farmed, mammal species in the years and months leading up to the COVID-19 pandemic. There are, however, no prior reports of which species, if any, were sold at the Huanan market in the months leading up to the pandemic. Here, we report that multiple plausible intermediate wildlife hosts of SARS-CoV-2 progenitor viruses, including red foxes (Vulpes vulpes), hog badgers (Arctonyx albogularis) and common raccoon dogs (Nyctereutes procyonoides), were sold live at the Huanan market up until at least November of 2019. No reports are known to be available for SARS-CoV-2 test results from these mammals at the Huanan market. Despite a general slow-down in live animal sales during the winter months, we report that raccoon dogs that are sold for both meat and fur were consistently available for sale throughout the year, including at the Huanan market in November 2019.

Positive environmental samples linked both to live mammal sales and to human cases at the Huanan market

We used a spatial relative risk analysis to identify potential regions of the market with an increased density of positive environmental samples. We found evidence (p<0.05) of a region in the southwest area of the market where live mammals were on sale. Although environmental sampling of the market was incomplete and spatially heterogeneous (data S1 and table S6), our analysis accounts for the empirical environmental sampling distribution, which was biased toward 'stalls related to December cases' as well as 'stalls that sold livestock, poultry, farmed wildlife'.The 'distance to the nearest vendor selling live mammals' and 'distance to the nearest human case' were independently predictive of environmental sample positivity (p=0.004 and 0.014, respectively for N=6; table S9).

To further investigate the robustness of these findings to possible sampling biases, we considered three scenarios: (i) oversampling of live mammal and unknown meat stalls, (ii) over-counting of positive samples, and (iii) exclusion of the seafood stand near the wildlife area of the market (with five positive samples) from our analysis (table S10). In each case, the distance to live mammal vendors remained predictive of environmental sample positivity, and the region of increased positive sample density in the southwest corner of the western section of the market remained consistent.