So, was the origin of the COVID pandemic bats?

In the early 2000s, a coronavirus that infected bats jumped to vivarium dogs (an Asian canid) and other wild mammals in southwest China. Some of these animals were sold at markets, where the coronavirus jumped again and jumped to humans. The result was the SARS pandemic, which spread to 33 countries and killed 774 people. A few months later, scientists discovered the coronavirus in mammals known as palm civets, which were being sold at a market at the center of the outbreak.

In a study published this week, a team of researchers compared the evolutionary history of SARS with that of COVID-19, 17 years later. The researchers analyzed the genomes of both coronaviruses that caused the pandemics, along with those of 248 related coronaviruses in bats and other mammals.

Jonathan Pekar, an evolutionary virologist at the University of Edinburgh and one of the authors of the new study, says the histories of both coronaviruses followed parallel paths. “In my opinion, they are remarkably similar,” he says.

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

“Selling wildlife in city centers means you can occasionally get a pandemic,” says Michael Worobey, an evolutionary biologist at the University of Arizona and a co-author of the new study.

Lab leak?

The study comes at a time of political tension. Last month, the White House created a website called "Lab Leak: The True Origin of Covid-19" claiming that the pandemic was caused not by a market spillover, but by an accident at a Wuhan lab.

A week ago, in its budget proposal, the White House deemed the Chinese lab leak "confirmed" and justified an $18 billion cut to the National Institutes of Health (NIH) in part by what it described as "its failure to demonstrate that funding is leaking."

The Chinese government's reaction was to flatly deny that Covid was caused by a Wuhan lab leak and to raise the possibility that the virus originated in a U.S. biodefense lab.

"A thorough and in-depth investigation into the origins of the virus in the United States should be conducted," the statement said.

For Sergei Pond, a virologist at Temple University, the origin of COVID-19 is unresolved. But he fears that the inflammatory language of both governments makes it difficult for scientists to investigate (and debate) its origins. "If it weren't tragic, it would be laughable—it's absolutely grotesque," says Pond. During the first weeks of the pandemic in early 2020, claims circulated that the virus causing the disease, SARS-CoV-2, was a biological weapon created by the Chinese military. A group of scientists who analyzed the data available at the time rejected this idea. Although they couldn't rule out an accidental lab leak, they leaned toward a natural origin for COVID-19.

As time passed, Dr. Worobey, who was not part of this group, grew increasingly unhappy that there was still not enough evidence to choose one theory and rule out the other. That's why he signed an open letter with 17 other scientists calling for more research to determine the most plausible explanation.

"It seems to us that there were a lot of things we don't know, so we're not ruling out the idea of a lab leak," Worobey says. "Let's look into it."

By the time Dr. Worobey and other scientists began studying the origins of COVID, American intelligence agencies were also involved. Their assessments have been mixed. The FBI and CIA argue for a leak from the Wuhan Institute of Virology, though with limited certainty. The Department of Energy is hesitant to believe the virus came from another lab in Wuhan. Other agencies lean toward a natural origin.

The agencies have not made their tests or analyses public, so scientists cannot assess the basis for their conclusions. However, Dr. Worobey and other researchers have published a number of articles in scientific journals. At one point, Dr. Worobey concluded that the COVID pandemic began at the Huanan Seafood Market in Wuhan.

"Scientifically, it's as clear as HIV or the Spanish flu," said Dr. Worobey, referring to two diseases he has also studied to determine their origins.

Mosaic Viruses

For the new study, Worobey, Pekar, and their colleagues compared the genomes of 250 coronaviruses using their genetic similarities and differences to determine their relatedness. They were able to piece together the history of the coronaviruses that cause both SARS and COVID-19, known as SARS-CoV and SARS-CoV-2.

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

The coronaviruses infected the bats and 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 original coronaviruses, a process known as recombination.

"These things are not ancient," says David Rasmussen, a virologist at North Carolina State University who was not involved in the new study. "These are things that happen all the time. These viruses are true mosaics."

In 2001, just a year before the SARS pandemic began in Guangzhou, researchers discovered that SARS-CoV had undergone its final genetic shuffling in bats. Only after this final recombination could the virus have become a human pathogen. And because Guangzhou is located several hundred kilometers from the region of SARS-CoV's origin, bats could not have brought the virus to the city in such a short time.

The general consensus among researchers is that the predecessors of SARS-CoV infected wild mammals that were subsequently 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 sold in markets.

Researchers found a similar pattern when they focused on SARS-CoV-2, the cause of COVID-19. The last recombination in bats occurred between 2012 and 2014—five to seven years before the COVID-19 pandemic, which originated several hundred kilometers northeast, in Wuhan.

An eye on wildlife

This city is also located considerably far from the region where the virus's predecessors had circulated. However, they made a journey comparable to that of SARS-CoV, courtesy of the wildlife trade.

Proponents of the lab-leak theory have highlighted the remoteness of Wuhan to the locations where SARS-CoV-2's closest relatives have been found. If bats couldn't fly to the area around Wuhan and infect wild mammals, they argue, scientists must have collected the coronavirus from bats in southwest China and manipulated it in their lab, from which it then escaped.

American scientists have criticized the Wuhan Institute of Virology for lax safety measures in its coronavirus experiments, but no one has offered evidence that the predecessor to SARS-CoV-2 was at the Wuhan Institute of Virology before the pandemic. The new study by Worobey and colleagues shows that bat coronaviruses can travel long distances without the help of scientists, via the wildlife trade.

The researchers argue that these findings are consistent with studies they published in 2022 that pointed to the Huanan Seafood Market in Wuhan as the place where the COVID pandemic began. In other studies, Worobey and his colleagues argued that the virus had spread twice, starting in the wild mammals that were sold at the market.

Pond believes the new study is consistent with the theory of a spillover from wild animals, but he believes the issue is not settled. He notes that two statisticians last year questioned the model behind the 2022 study. Worobey and a colleague have since countered this criticism. "The debate is still ongoing," Pond says.

Marc Eloit, former director of the Pathogen Discovery Laboratory at the Pasteur Institute in Paris, believes the new study is relevant because it provides a clear view of the origin of SARS-CoV-2. Eloit, however, also notes that the coronavirus was remarkably different from its closest known relatives in bats. After diverging from these viruses, it must have mutated or undergone recombination to adapt well and spread among humans.

"I maintain that the possibility of recombination, whether accidental or deliberate, in a laboratory setting remains as plausible as the hypothesis of the virus emerging through an intermediary host at a market," Eloit says.

This researcher and other scientists agree that finding an intermediate form of SARS-CoV-2 in a wild mammal would provide a compelling argument for natural spread. Chinese authorities tested some animals early in the pandemic and didn't find the virus.

Now, wildlife vendors at the Huanan market removed the animals from their stalls before scientists could study them. And as soon as China halted wildlife sales, farmers euthanized their animals.

"There's a big missing piece here, and this is a fact we can't get away from," Pond says.

Stephen Goldstein, a geneticist at the University of Utah who was not involved in the new study, says the research serves as a cautionary tale about the risk of a future coronavirus pandemic. Wild mammals sold at markets anywhere in the region where SARS and COVID began could become a vehicle to a city hundreds of miles away. "Pieces of these viruses exist in all these places," Goldstein says.

Translation by Marc Rubió