Genetic Study Retraces Covid’s Origins in Bats

In the early 2000s, a coronavirus infecting bats jumped into raccoon dogs and other wild mammals in southwestern China. Some of those animals were sold in markets, where the coronavirus jumped again, into humans. The result was the SARS pandemic, which spread to 33 countries and claimed 774 lives. A few months into it, scientists discovered the coronavirus in mammals known as palm civets sold in a market at the center of the outbreak.

In a study published on Wednesday, a team of researchers compared the evolutionary story of SARS with that of Covid 17 years later. The researchers analyzed the genomes of the two coronaviruses that caused the pandemics, along with 248 related coronaviruses in bats and other mammals.

Jonathan Pekar, an evolutionary virologist at the University of Edinburgh and an author of the new study, said that the histories of the two coronaviruses followed parallel paths. “In my mind, they are extraordinarily similar,” he said.

In both cases, Dr. Pekar and his colleagues argue, a coronavirus jumped from bats to wild mammals in southwestern China. In a short period of time, wildlife traders took the infected animals hundreds of miles to city markets, and the virus wreaked havoc in humans.

“When you sell wildlife in the heart of cities, you’re going to have a pandemic every so often,” said Michael Worobey, an evolutionary biologist at the University of Arizona and an author of the new study.

The study lands at a fraught political moment. Last month the White House created a web page called “Lab Leak: The True Origin of Covid 19,” asserting that the pandemic had been caused not by a market spillover but by an accident in a lab in Wuhan, China.

On Friday, in its proposed budget, the White House described the lab leak as “confirmed” and justified an $18 billion cut to the National Institutes of Health in part on what it described as the agency’s “inability to prove that its grants to the Wuhan Institute of Virology were not complicit in such a possible leak.”

The Chinese government responded with a flat denial that Covid had been caused by a Wuhan lab leak and raised the possibility that the virus had come instead from a biodefense lab in the United States.

“A thorough and in-depth investigation into the origins of the virus should be conducted in the U.S.,” the statement read.

Sergei Pond, a virologist at Temple University, said that he did not consider the origin of Covid settled. But he worried that the incendiary language from the two governments would make it difficult for scientists to investigate — and debate — the origin of Covid.

“If it wasn’t tragic, you’d have to laugh, it’s so farcical,” Dr. Pond said.

In the first weeks of the Covid pandemic in early 2020, claims circulated that the virus responsible, SARS-CoV-2, was a biological weapon created by the Chinese Army. A group of scientists who analyzed the data available at the time rejected that idea. Although they couldn’t rule out an accidental lab leak, they favored a natural origin of Covid.

As time passed, Dr. Worobey, who was not part of that group, became frustrated that there was not yet enough evidence to choose one theory over the other. He signed an open letter with 17 other scientists calling for more investigation to determine which explanation was more likely.

“To us it seemed that there was a lot we don’t know, so let’s not discard the lab-leak idea,” Dr. Worobey said. “Let’s study it.”

As Dr. Worobey and other scientists started studying the origin of Covid, American intelligence agencies were also assessing it. Their assessments have been mixed. The F.B.I., and the C.I.A. favor an escape from the Wuhan Institute of Virology, although with only low certainty. The Department of Energy leans with low confidence to the virus escaping from a different lab in Wuhan. Other agencies lean toward a natural origin.

The agencies have not made their evidence or their analyses public, and so scientists cannot evaluate the basis of their conclusions. However, Dr. Worobey and other researchers have published a string of papers in scientific journals. Along the way, Dr. Worobey became convinced that the Covid pandemic had started at the Huanan Seafood Market in Wuhan.

“Scientifically, it’s as clear as H.I.V. or Spanish flu,” Dr. Worobey said, referring to two diseases whose origins he has also studied.

For the new study, Dr. Worobey, Dr. Pekar and their colleagues compared the genomes of 250 coronaviruses, using their genetic similarities and differences to determine their relationships. They were able to reconstruct the history of the coronaviruses that cause both SARS and Covid — known as SARS-CoV and SARS-CoV-2.

The ancestors of both coronaviruses circulated in bats across much of China and neighboring countries for hundreds of thousands of years. In the last 50 years or so, their direct ancestors infected bats that lived in southwestern China and northern Laos.

As the coronaviruses infected the bats, they sometimes ended up inside a cell with another coronavirus. When the cell made new viruses, it accidentally created hybrids that carried genetic material from both of the original coronaviruses — a process known as recombination.

“These aren’t ancient events,” said David Rasmussen, a virologist at North Carolina State University who was not involved in the new study. “These things are happening all the time. These viruses are truly mosaics.”

In 2001, just a year before the SARS pandemic started in the city of Guangzhou, the researchers found, SARS-CoV underwent its last genetic mixing in bats. Only after that last recombination could the virus have evolved into a human pathogen. And since Guangzhou is several hundred miles from the ancestral region of SARS-CoV, bats would not have been able to bring the virus to the city in so little time.

Instead, researchers generally agree, the ancestors of SARS-CoV infected wild mammals that were later sold in markets around Guangzhou. A few months after the start of the SARS pandemic, researchers discovered SARS-CoV in palm civets and other wild mammals for sale in markets.

The researchers found a similar pattern when they turned to SARS-CoV-2, the cause of Covid. The last recombination in bats took place between 2012 and 2014, just five to seven years before the Covid pandemic, several hundred miles to the northeast, in Wuhan.

That was also a substantial departure from the region where the virus’s ancestors had circulated. But it was comparable to the journey that SARS-CoV took, courtesy of the wildlife trade.

Proponents of lab-leak theories have highlighted the long distance between Wuhan and the locations where the closest relatives of SARS-CoV-2 have been found. If bats could not fly to the region around Wuhan and infect wild mammals there, they maintain, then scientists must have collected the coronavirus from bats in southwest China and tinkered with it in their lab, from which it then escaped.

American scientists have criticized the Wuhan Institute of Virology for lax safeguards in their coronavirus experiments. But no one has offered evidence that the progenitor of SARS-CoV-2 was at the Wuhan Institute of Virology before the pandemic. The new study by Dr. Worobey and his colleagues shows that bat coronaviruses can travel long distances without the help of scientists, through the wildlife trade.

The researchers argue that these findings agree with studies that they published in 2022, which pointed to the Huanan Seafood Market in Wuhan as the place where the Covid pandemic got its start. Wild mammals were sold there; many early cases of Covid were recorded there, and Chinese researchers collected different strains of SARS-CoV-2 carrying distinct mutations there. Dr. Worobey and his colleagues argued that the virus had twice spilled over from wild mammals at the market.

Dr. Pond said that the new study was consistent with the theory of a wildlife spillover. But he does not consider the matter settled. He noted that last year two statisticians took issue with the model behind the 2022 study. Dr. Worobey and a colleague have countered that criticism. “That debate is still ongoing,” Dr. Pond said.

Marc Eloit, the former director of the Pathogen Discovery Laboratory at Pasteur Institute in Paris, said that the new study was significant for providing a clear picture of where SARS-CoV-2 came from.

But he also observed that the coronavirus was markedly different from its closest known relatives in bats. After it split from those viruses, it must have mutated or undergone recombination to become well adapted for spreading in humans.

“I maintain that the possibility of a recombination event — whether accidental or deliberate — in a laboratory setting remains just as plausible as the hypothesis of emergence via an intermediate host on the market,” Dr. Eloit said.

Dr. Eloit and other scientists agreed that finding an intermediate form of SARS-CoV-2 in a wild mammal would make a compelling case for a natural spillover. Chinese authorities looked at some animals at the start of the pandemic and did not find the virus in them.

However, wildlife vendors at the Huanan market removed their animals from the stalls before scientists could study them. And once China put a stop to wildlife sales, farmers culled their animals.

“There’s a big missing piece, and you really can’t dance around it,” said Dr. Pond.

Stephen Goldstein, a geneticist at the University of Utah who was not involved in the new study, said that the research served as a warning about the risk of a future coronavirus pandemic. Wild mammals sold in markets anywhere in the region where SARS and Covid got their start could become a vehicle to a city hundreds of miles away. “The pieces of these viruses exist in all these places,” Dr. Goldstein said.