Genetic tracing at the Huanan Seafood Market further supports the animal origin of COVID

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A new international collaborative study provides a list of the animal species present on the market from which SARS-CoV-2, the virus responsible for the COVID-19 pandemic, most likely originated in late 2019. The study is based on a new analysis of metatranscriptomic data released by the Chinese Center for Disease Control and Prevention (CDC). The data comes from more than 800 samples collected in and around the Huanan Seafood Wholesale Market from January 1, 2020, and from viral genomes reported from early COVID-19 patients. The research will appear in the magazine on September 19 Cell.

“This is one of the most important datasets that exist on the origins of the COVID-19 pandemic,” says co-corresponding author Florence Débarre from the French National Center for Scientific Research (CNRS). “We are extremely grateful that the data exists and is being shared.”

“This article adds a new layer to the mounting evidence that all points to the same scenario: that infected animals were introduced into the market in mid-to-late November 2019, triggering the pandemic,” said co-corresponding author Kristian Andersen from Scripps Research. .

“We analyzed in new and rigorous ways the critically important data collected by the Chinese CDC team,” said co-corresponding author Michael Worobey of the University of Arizona. “This is an authoritative analysis of that data and how it fits with the rest of the vast body of evidence we have about how the pandemic started.”

On January 1, 2020, after the animals had been removed and just hours after the market closed, researchers from the China CDC went to the market to collect samples. They swept the floors, walls, and other surfaces of the stables; Days later, they returned to focus on surfaces in wildlife stalls, such as a cage and carts used to move animals, and then also collected samples from the drains and sewers.

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They performed metatranscriptomic sequencing of the samples, a technique that aims to obtain all RNA sequences (and can also pick up DNA) of all organisms present in the samples: viruses, bacteria, plants, animals and humans. The Chinese CDC team, led by Liu Jun, published their data and results in the journal in 2023 Nature. However, the paper left unresolved the exact identity of the animal species found in the data that could represent plausible intermediate hosts. The Chinese CDC shared their sequencing data on public and open repositories.

According to the latest analysis of this data, published in CellSARS-CoV-2 was present in some of the same stalls as wild animals sold at the market – including raccoon dogs (small fox-like animals with markings similar to raccoons) and civet cats (small carnivorous mammals related to mongooses and hyenas) . In some cases, genetic material from the SARS-CoV-2 virus and these animals was even found on the same swabs. The exact animal species were identified by genotyping their mitochondrial genomes in the samples.

“Many of the major species had been culled before the Chinese CDC teams arrived, so we cannot have direct evidence that the animals were infected,” Débarre said. “We see the DNA and RNA ghosts of these animals in the environmental samples, and some are in stables where SARS-CoV-2 was also found. This is what you would expect in a scenario where there were infected animals on the market. .”

“These are the same species of animals that we know caused the original SARS coronavirus to spread to humans in 2002,” Worobey added. ‘This is the riskiest thing we can do: take wild animals that are full of viruses and then play with fire by bringing them into contact with people who live in the heart of big cities, where population density makes it easy for these viruses to survive. to cling.”

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The international team also conducted an evolutionary analysis of the earliest viral genomes reported during the pandemic, including these environmental sequences, and deduced the most likely precursor genotypes of the virus that infected humans and led to the COVID-19 pandemic. The results imply that very few, if any, people were infected before the market outbreak. This is consistent with the spillover effects from animals to humans within the market. There may also have been spillovers with limited impact into the immediate upstream pet trade.

“In this paper we show that the sequences associated with the market are consistent with the emergence of a market,” says Débarre. “The key diversity of SARS-CoV-2 was on the market from the very beginning.”

The new study shortlisted wet market animal species that co-occur or are close to viral samples and could be the most likely intermediate hosts for SARS-CoV-2. The common raccoon dog, a species susceptible to SARS-CoV-2 that carried SARS-CoV in 2003, was found to be genetically the most common animal in samples from market animal stalls. Genetic material from masked palm civets, which were also linked to the previous SARS-CoV outbreak, was also found in a stable containing SARS-CoV-2 RNA. Other species such as the gray bamboo rat and Malayan porcupines were also found to be present in SARS-CoV-2 positive samples, as well as a large number of other species.

While the data cannot prove whether one or more of these animals may have been infected, the team’s analyzes provide a clear list of the species that could most plausibly have carried the virus, and genetic information that can be used to to help trace where they come from.

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The researchers emphasize the importance of understanding the origins of the COVID-19 pandemic, especially in light of other recent spillover effects, such as the spread of bird flu viruses in livestock in the United States. “There has been a lot of misinformation and misinformation about the origins of SARS-CoV-2,” Worobey said. “The reason it’s so important to find out is because this has national security and public health implications, not just in the United States but around the world. And the truth is that since the pandemic began more than four years ago, even though there has been an increase in laboratory safety, not much has been done to reduce the chance of a zoonotic scenario happening again.”

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