NOT PRODUCED IN A LAB
Samples from Huanan Seafood Market provide further evidence of COVID-19 animal origins
A new analysis co-authored by University of Arizona virus expert Michael Worobey provides additional evidence that wildlife sold illegally at a Chinese market were "ground zero" for the COVID pandemic.
University of Arizona
image:
Professional sterilization teams can be seen outside the main entrance of the Huanan Seafood Wholesale Market in Wuhan, China in March 2020, shortly after its closure.
view moreCredit: China News Service/Wikipedia
A new international study provides a shortlist of the wildlife species present at the market from which SARS-CoV-2, the virus responsible for the COVID-19 pandemic, most likely arose in late 2019.
The study, published Thursday in the journal Cell, is based on an analysis of genetic data released by the Chinese Center for Disease Control and Prevention. The data comes from more than 800 samples collected in and around the Huanan Seafood Wholesale market in Wuhan, China, beginning on Jan. 1, 2020, and from viral genomes from early COVID-19 patients.
"This may be the last big, new set of data directly from the market, and in a way, it's like finishing the last piece of a puzzle showing a picture that has been pretty clear already," said Michael Worobey, one of three co-corresponding authors on the paper and head of the Department of Ecology and Evolutionary Biology at the University of Arizona. "We present a thorough and rigorous analysis of the data and how it fits in with the rest of the huge body of evidence we have about how the pandemic started."
On Jan. 1, 2020, just hours after the market closed, investigators from the Chinese CDC went to the market to collect samples. Although they encountered little in the way of live wildlife, they swabbed the floors, walls and other surfaces of many stalls. They came back days later to focus on surfaces in stalls where wildlife was sold, such as a cages and carts used to move animals, and also collected samples from drains and sewers.
They performed metatranscriptomic sequencing of the samples, a technique used to obtain RNA sequences (and which can pick up DNA as well) from all organisms present in the samples – viruses, bacteria, plants, animals and humans. The Chinese CDC team, led by Liu Jun, published its data and results in 2023 in the journal Nature. However, the article left unresolved the exact identities of the animal species found in the data. The Chinese CDC shared the sequencing data on public and open repositories.
According to the latest analysis of the data, SARS-CoV-2 was present in some of the same stalls where wildlife was sold at the market. That wildlife included raccoon dogs – small foxlike 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 were found on the same swabs.
"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," said co-corresponding author Florence Débarre of the French National Centre for Scientific Research. "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. This is what you would expect under a scenario in which there were infected animals in the market."
'Spark in a tinderbox'
Putting wild animals with viruses in contact with humans in the heart of big cities, where population densities make it easy for these viruses to take hold, is one of the most risky things humans can do, Worobey said.
"Not all of those viruses have the potential to start a pandemic, but when you do bring them in, it's like a spark in a tinderbox," he said.
The researchers also performed evolutionary analysis of the earliest viral genomes reported in the pandemic. The results imply that there were very few, if any, humans infected prior to the market outbreak. This is consistent with spillovers from animals to humans within the market, then subsequent spread throughout Wuhan and, eventually, the whole world, Worobey said.
While the data cannot prove whether one or more of these animals were infected, the analyses provide a clear list of the species that most likely could have carried the virus.
The study also presents the most complete record of animal species and specific populations within those species that could have acted as intermediate hosts at the market, Worobey said.
"It gives us clues about the populations that were represented there for each species," he said. "Where in Southeast Asia did they live? Where might they have come from? How many were farmed versus wild-caught and then moved into the transportation networks of illegal wildlife?"
Although there has been an increased focus on lab safety since the pandemic began more than four years ago, Worobey says "surprisingly little has been done to decrease the risk of a virus jumping from wildlife into humans again."
"We need to start putting the evidence of how this pandemic started into action by taking serious, concrete action to stop the perilous practice of bringing live animals with potential pandemic pathogens into densely populated urban areas," he said.
Michael Worobey, one of three co-corresponding authors on the paper, heads the Department of Ecology and Evolutionary Biology at the University of Arizona.
Credit
Beatriz Verdugo/University of Arizona
Journal
Cell
Method of Research
Data/statistical analysis
Subject of Research
Animals
Article Title
Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic
Article Publication Date
19-Sep-2024
Genetic tracing at the Huanan Seafood market further supports COVID animal origins
Cell Press
A new international collaborative study provides a list of the wildlife species present at the market from which SARS-CoV-2, the virus responsible for the COVID-19 pandemic, most likely arose 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 come from more than 800 samples collected in and around the Huanan Seafood Wholesale market beginning on January 1, 2020, and from viral genomes reported from early COVID-19 patients. The research appears September 19 in the journal Cell.
“This is one of the most important datasets that exists on the origin of the COVID-19 pandemic,” says co-corresponding author Florence Débarre of the French National Centre for Scientific Research (CNRS). “We’re extremely grateful that the data exist and were shared.”
“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 co-corresponding author Kristian Andersen of Scripps Research.
“We have analyzed, in new and rigorous ways, the vitally important data that the Chinese CDC team collected,” says co-corresponding author Michael Worobey of the University of Arizona. “This is an authoritative analysis of that data and how it fits in with the rest of the huge body of evidence we have about how the pandemic started.”
On January 1, 2020, after the animals were removed and just hours after the market was closed, investigators from the Chinese CDC went to the market to collect samples. They swabbed the floors, walls, and other surfaces of the stalls; they came back days later to focus on surfaces in stalls selling wildlife, such as a cage and carts used to move animals, and then also collected samples from the drains and sewers.
They performed metatranscriptomic sequencing of the samples, a technique aiming to obtain all RNA sequences (and which can pick up DNA as well) from all organisms present in the samples—viruses, bacteria, plants, animals, humans. The Chinese CDC team, led by Liu Jun, published their data and results in 2023 in the journal Nature. However, the article left unresolved the exact identities 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 these data being published in Cell, SARS-CoV-2 was present in some of the same stalls as wildlife 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 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. This is what you would expect under a scenario in which there were infected animals in the market.”
“These are the same sorts of animals that we know facilitated the original SARS coronavirus jumping into humans in 2002,” Worobey adds. “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.”
The international team also performed evolutionary analysis of the earliest viral genomes reported in the pandemic, including these environmental sequences, and inferred the most likely progenitor genotypes of the virus that infected humans and led to the COVID-19 pandemic. The results imply that there were very few, if any, humans infected prior to the market outbreak. This is consistent with spillovers from animals to humans within the market. There may also have been spillovers of limited impact in the immediate upstream animal trade.
“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.”
The new study landed on a short list of animal species in the wet market found co-occurring or close to viral samples that could represent the most likely intermediate hosts for SARS-CoV-2. The common raccoon dog, a species susceptible to SARS-CoV-2 and that carried SARS-CoV in 2003, was found to be the most genetically abundant animal in the samples from market wildlife stalls. Genetic material from masked palm civets, which were also associated with the earlier outbreak of SARS-CoV, was also found in a stall with SARS-CoV-2 RNA. Other species such as the Hoary bamboo rat and Malayan porcupines were also found to be present in SARS-CoV-2-positive samples, as well as a multitude of other species.
While the data cannot prove whether one or more of these animals may have been infected, the team’s analyses provide a clear list of the species that most plausibly could have carried the virus and genetic information that could be used to help trace where they originated.
The investigators stress the importance of understanding the origins of the COVID-19 pandemic, especially in light of other recent spillovers, such as the spread of avian flu viruses in cattle in the United States. “There has been a lot of disinformation and misinformation about where SARS-CoV-2 originated,” Worobey says. “The reason it’s so important to find out is that this affects national security and public health, not just in the United States but around the world. And the truth is, 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.”
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Funding information can be found in the text of the paper.
Cell, Crits-Christoph et al. “Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic” https://cell.com/cell/fulltext/S0092-8674(24)00901-2
Cell (@CellCellPress), the flagship journal of Cell Press, is a bimonthly journal that publishes findings of unusual significance in any area of experimental biology, including but not limited to cell biology, molecular biology, neuroscience, immunology, virology and microbiology, cancer, human genetics, systems biology, signaling, and disease mechanisms and therapeutics. Visit http://www.cell.com/cell. To receive Cell Press media alerts, contact press@cell.com.
Journal
Cell
Method of Research
Data/statistical analysis
Subject of Research
Not applicable
Article Title
Genetic tracing of market wildlife and viruses at the epicenter of the COVID-19 pandemic
Article Publication Date
19-Sep-2024
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