New Study Identifies Animals Likely Behind SARS-CoV-2 at Wuhan's Huanan Market

The virus responsible for COVID-19 seems to have made its initial jump into humans from captive wild animals at Wuhan's Huanan seafood market. A new study now points to particular animal species that likely harboured the virus.

Drawing on metagenomic RNA data gathered soon after the market was closed, the fresh analysis also strengthens the growing body of evidence concerning the origin of SARS-CoV-2.

SARS-CoV-2 origins and the Huanan market

The earliest warning signs emerged in Wuhan, the capital of China's Hubei province, in late 2019. As well as the now-closed seafood and animal market, the city hosts the Wuhan Institute of Virology (WIV), whose scientists have researched coronaviruses.

Although research indicates that SARS-CoV-2 was not created in a laboratory, its appearance in the same city as the WIV has prompted suspicion and extensive speculation. One widely discussed theory holds that, even if the virus developed naturally, it might have escaped after researchers collected it in the wild.

Yet evidence for a laboratory leak remains limited. Many virologists consider it much more likely that the virus passed to people from one of the many mammals sold at the Huanan market, where the circumstances were well suited to a zoonotic spillover.

Seeking greater certainty, an international research team examined data collected by the Chinese Center for Disease Control and Prevention (CDC) in early 2020.

"This is one of the most important datasets that exists on the origin of the COVID-19 pandemic," says the study's senior author, evolutionary biologist Florence Débarre of the French National Centre for Scientific Research (CNRS).

"We're extremely grateful that the data exist and were shared."

Environmental samples from Wuhan's Huanan market

Chinese CDC investigators entered the Huanan market on New Year's Day 2020, just hours after it was shut because of COVID. The animals had already been removed, but the investigators collected environmental samples.

They first swabbed surfaces in stalls where animals had been kept. Several days later, they came back to swab further stalls, cages and carts, while also taking samples from drains and sewers.

The researchers additionally used metatranscriptomic sequencing to identify every RNA sequence from every organism found in the samples, as well as some DNA. They compared these data with samples from early SARS-CoV-2 cases recorded up to 14 February 2020.

The Chinese CDC team reported its results in Nature in 2023. In total, it collected more than 800 samples and, although it did not identify animals as possible intermediate hosts of SARS-CoV-2, it made the sequencing data available through open-access repositories.

This allowed the subsequent analysis, whose authors say they identified animal species in the samples by genotyping mitochondrial genomes.

Débarre, first author and microbiologist Alexander Crits-Christoph, and their colleagues detected evidence of the virus in stalls that had contained animals, including raccoon dogs and civets. Certain swabs even contained both animal genetic material and SARS-CoV-2.

"Many of the key animal species had been cleared out before the Chinese CDC teams arrived, so we can't have direct proof that the animals were infected," Débarre says.

"We are seeing the DNA and RNA ghosts of these animals in the environmental samples, and some are in stalls where SARS-CoV-2 was found, too," she adds. "This is what you would expect under a scenario in which there were infected animals in the market."

Raccoon dogs, civets and possible intermediate hosts

The research also carried out an evolutionary assessment of viral genomes from the earliest days of COVID, looking for likely ancestors of the virus that began the pandemic. Its findings indicate that few, if any, people were infected before outbreaks associated with the market.

"In this paper, we show that the sequences linked to the market are consistent with a market emergence," Débarre says. "The main diversity of SARS-CoV-2 was in the market from the very beginning."

From these results, the authors produced a shortlist of species sold at the market that were most likely to have acted as intermediate hosts.

They found that the common raccoon dog (Nyctereutes procyonoides) was the genetically most abundant animal in the samples. Genetic material from the masked palm civet (Paguma larvata) was also identified in a stall containing SARS-CoV-2 RNA.

The researchers note that both species were associated with the original SARS outbreak, while common raccoon dogs are known to be susceptible to SARS-CoV-2.

"These are the same sorts of animals that we know facilitated the original SARS coronavirus jumping into humans in 2002," says ecologist Michael Worobey of the University of Arizona.

"This is the most risky thing we can do – take wild animals that are teeming with viruses and then play with fire by bringing them into contact with humans living in the heart of big cities, whose population densities make it easy for these viruses to take hold," Worobey adds.

Although the new study does not demonstrate that any animals were infected with SARS-CoV-2, it provides leads that may help future investigations and further reinforces the Huanan market's role as the starting point of COVID.

"This paper adds another layer to the accumulating evidence that all points to the same scenario: that infected animals were introduced into the market in mid- to late November 2019, which sparked the pandemic," says evolutionary biologist Kristian Andersen of the Scripps Research Institute in the US.

This matters both for retrospective research into COVID's origins and for efforts to prevent future pandemics.

"Since the pandemic started more than four years ago, although there has been an increased focus on lab safety, not much has been done to decrease the chance of a zoonotic scenario like this happening again," Worobey says.

The study was published in Cell.