Ever since the dawn of the COVID-19 pandemic, rumours have swirled that the source of the virus was a lab leak - either of a manufactured bio-weapon, or of a natural virus.
But a new study has traced the start of the pandemic, and concluded that live animals sold at the Huanan Seafood Wholesale Market were the source of the virus.
The market saw foxes, raccoon dogs and other live mammals susceptible to the virus on sale immediately before the pandemic began.
Two papers on the research were published in the journal Science.
The publications “virtually eliminate” alternative scenarios that have been suggested as origins of the pandemic, the researchers say.
The researchers say that the first spread to humans from animals likely occurred in two separate transmission events in the Huanan market in late November 2019.
The first, led by Worobey and Kristian Andersen at Scripps Research Institute in San Diego, California, examined the geographic pattern of COVID-19 cases in the first month of the outbreak, December 2019.
The team was able to determine the locations of almost all of the 174 COVID-19 cases identified by the World Health Organisation that month, 155 of which were in Wuhan.
Analyses showed that these cases were clustered tightly around the Huanan market, whereas later cases were dispersed widely throughout Wuhan.
The researchers found that people with no direct connection to the market – meaning they neither worked there nor shopped there – turned out to live near the market.
Worobey said: "In a city covering more than 3,000 square miles, the area with the highest probability of containing the home of someone who had one of the earliest COVID-19 cases in the world was an area of a few city blocks, with the Huanan market smack dab inside it.”
By January and February 2020, cases were spreading in the areas of the highest population density in Wuhan.
Worobey said: "This tells us the virus was not circulating cryptically. It really originated at that market and spread out from there."
The study also looked at swab samples taken from market surfaces like floors and cages after Huanan market was shuttered.
Samples that tested positive for SARS-CoV-2 were significantly associated with stalls selling live wildlife.
The researchers determined that mammals now known to be susceptible to SARS-CoV-2, including red foxes, hog badgers and raccoon dogs, were sold live at the Huanan market in the weeks preceding the first recorded COVID-19 cases.
The scientists developed a detailed map of the market and showed that SARS-CoV-2-positive samples reported by Chinese researchers in early 2020 showed a clear association with the western portion of the market, where live or freshly butchered animals were sold in late 2019.
The second study, an analysis of SARS-CoV-2 genomic data from early cases, was co-led by Jonathan Pekar and Joel Wertheim at the University of California, San Diego and Marc Suchard of the University of California Los Angeles, as well as Andersen and Worobey.
The researchers determined that the pandemic, which initially involved two subtly distinct lineages of SARS-CoV-2, likely arose from at least two separate infections of humans from animals at the Huanan market in November 2019 and perhaps in December 2019.
The authors used a technique known as molecular clock analysis, which relies on the natural pace with which genetic mutations occur over time, to establish a framework for the evolution of the SARS-CoV-2 virus lineages.
They found that a scenario of a singular introduction of the virus into humans rather than multiple introductions would be inconsistent with molecular clock data.
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