By Daniel Stolte, University Communications

Tuesday

Live animals sold at Huanan Seafood Wholesale Market in Wuhan, China, have been confirmed by an international team of researchers as the likely source of the COVID-19 pandemic that has claimed 6.4 million lives since then. its appearance almost three years ago.

Led by a University of Arizona viral evolution expert Michael Worobey, the researchers traced the start of the pandemic to the Wuhan market, where live foxes, raccoon dogs and other mammals susceptible to the virus were sold just before the start of the pandemic. Their findings were published in two articles in the journal Science on Tuesday, having previously been published in preprint versions in February.

The publications, which have since been peer-reviewed and include additional analysis and conclusions, virtually eliminate the alternative scenarios that have been suggested as the origins of the pandemic. Additionally, the authors conclude that the first spread to humans from animals likely occurred during two separate transmission events in the Huanan market in late November 2019.

A study looked at the locations of the earliest known cases of COVID-19, as well as swab samples taken from surfaces at various market locations. The other study focused on SARS-CoV-2 genomic sequences from samples taken from COVID-19 patients during the early weeks of the pandemic in China.

The first paper, led by Worobey and Kristian Andersen of Scripps Research in San Diego, Calif., looked at the geographic distribution of COVID-19 cases during the first month of the outbreak, in December 2019. Researchers were able to determine the locations of nearly all of the 174 COVID-19 cases identified by the World Health Organization that month, including 155 in Wuhan.

Analyzes showed that these cases were tightly clustered around the Huanan market, while later cases were widely scattered throughout Wuhan – a city of 11 million people. Notably, the researchers found that a striking percentage of early COVID patients with no known connection to the market — meaning they didn’t work or shop there — lived near the market. This confirms the idea that the market was the epicenter of the outbreak, Worobey said, with vendors being the first to be infected and setting off a chain of infections among nearby community members.

“In a city spanning over 3,000 square miles, the area with the highest likelihood of containing the home of someone who had one of the world’s first cases of COVID-19 was an area of ​​a few city blocks, with Huanan Market dabbing inside,” said Worobey, who leads UArizona Department of Ecology and Evolutionary Biology.

This conclusion was supported by another finding: When the authors looked at the geographic distribution of subsequent COVID cases, from January to February 2020, they found a “polar opposite” pattern, Worobey said. While the December 2019 cases were charted “as a target” in the market, the latest cases coincided with areas of highest population density in Wuhan.

“This tells us that the virus was not circulating in an encrypted fashion,” Worobey said. “It was really born in that market and spread from there.”

In an important addition to their earlier findings, Worobey and his collaborators addressed the question of whether health authorities found cases on the market simply because that’s where they looked.

“It’s important to realize that all of these cases were people who were identified because they were hospitalized,” Worobey said. “None were mild cases that could have been identified by knocking on the doors of people who lived near the market and asking them if they felt sick. In other words, these patients were registered because they were in the hospital, not because of where they lived.”

To rule out any possibility of potentially lingering bias, the Worobey team took it a step further: starting with the market, they started removing cases from their analyses, moving away from the market as they went, and again analyzed the statistics. The result: Even when two-thirds of the cases were removed, the results were the same.

“Even in this scenario, with the majority of cases suppressed, we found that the rest lived closer to the market than one would expect if there was no geographic correlation between these early COVID cases. and the market,” Worobey said.

The study also looked at swab samples taken from market surfaces such as floors and cages after the Huanan Market closed. Samples testing positive for SARS-CoV-2 were significantly associated with stalls selling live wild animals.

Researchers have determined that mammals now known to be susceptible to SARS-CoV-2, including red foxes, hog badgers and raccoon dogs, were sold alive in the Huanan market in the weeks preceding the first cases. of registered COVID-19. 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 part of the market, where live or freshly slaughtered animals were sold at the end of 2019. .

“The upstream events are still unclear, but our analyzes of the available evidence clearly suggest that the pandemic originated from initial human infections from animals for sale at the Huanan Seafood Wholesale Market in late November 2019,” said Andersen, co-lead author of both studies and is a professor in the Department of Immunology and Microbiology at Scripps Research.

The virus has likely jumped from animals to humans more than once

The second study, an analysis of SARS-CoV-2 genomic data from early cases, was co-led by Jonathan Pekar and Joel Wertheim of the University of California, San Diego, and Marc Suchard of the University of California, Los Angeles. , as well as Andersen and Worobey.

The researchers combined epidemic modeling with analyzes of the early evolution of the virus based on the first sampled genomes. They determined that the pandemic, which initially involved two subtly distinct lineages of SARS-CoV-2, likely originated from at least two separate infections of humans from animals at the Huanan market in November 2019 and possibly in December 2019. Analyzes also suggested that during this period there were numerous other transmissions of the virus from animals to humans in the marketplace that did not manifest in recorded cases of COVID -19.

The authors used a technique known as molecular clock analysis, which relies on the natural rate at which genetic mutations occur over time, to establish a framework for the evolution of lineages of the SARS-CoV-2 viruses. They found that a scenario of single introduction of the virus into humans rather than multiple introductions would be inconsistent with the molecular clock data. Previous studies had suggested that one lineage of the virus – named A and closely related to viral relatives in bats – gave rise to a second lineage, named B. More likely, according to the new data, is a scenario in which the two lines jumped from animals to humans on separate occasions, both in the Huanan market, Worobey said.

“Otherwise, the A line would have had to evolve in slow motion compared to the B line virus, which just doesn’t make biological sense,” Worobey said.

Both studies provide evidence that COVID-19 originated from animal-to-human jumps in the Huanan market, likely as a result of transmission to those animals from bats carrying coronaviruses in the wild or in the wild. farms in China. Going forward, the researchers say scientists and public officials should seek to better understand the wildlife trade in China and elsewhere and promote more comprehensive testing of live animals sold in markets to reduce the risk of future pandemics.

Funding for the research was provided primarily by the National Institutes of Health and the National Science Foundation. For a full list of funding sources, please see the research papers.