The ancestor of the virus that causes COVID-19 left its point of origin in Western China or Northern Laos just several years before the disease first emerged in humans up to 2,700 kilometers away in Central China, according to a new study by University of California San Diego School of Medicine researchers and their colleagues.

That’s not enough time for the evolving virus to have been carried there via the natural dispersal of its primary host, the horseshoe bat. This has led the researchers to conclude that it instead hitched a ride there with other animals via the wildlife trade, consistent with what happened during the SARS outbreak in 2002. The study was published in Cell on May 7.

Horseshoe bats are the main hosts of sarbecoviruses. These viruses don’t harm the bats, but are thought to have made the leap to humans through “zoonotic spillover” events. Sarbecoviruses gave rise to severe acute respiratory syndrome-related coronaviruses including SARS-CoV-1, the strain that caused the SARS pandemic of 2002-2004, and SARS-CoV-2, the strain that resulted in the COVID-19 pandemic. How they got to the places where these events occurred and whether animals besides bats were involved has been a matter of ongoing debate, however.

To clarify these questions, the researchers analyzed the family tree of both viral strains using genome sequence data available online, mapping their evolutionary history across Asia before they emerged in humans. However, the picture was blurred by the fact that these RNA viruses undergo a large amount of recombination inside their bat hosts, exchanging genetic material.

“When two different viruses infect the same bat, sometimes what comes out of that bat is an amalgam of different pieces of both viruses,” said co-senior author Joel Wertheim, Ph.D., a professor of medicine at UC San Diego School of Medicine’s Division of Infectious Diseases and Global Public Health. “Recombination complicates our understanding of the evolution of these viruses because it results in different parts of the genome having different evolutionary histories.”

The researchers avoided that problem by identifying all of the non-recombining regions of the viral genomes and using those to recreate the evolutionary history of the viruses instead.

The study found that sarbecoviruses related to SARS-CoV-1 and SARS-CoV-2 have circulated around Western China and Southeast Asia for millennia. During this time, they moved around the landscape at similar rates as their horseshoe bat hosts.

“Horseshoe bats have an estimated foraging area of around 2-3 km and a dispersal capacity similar to the diffusion velocity we estimated for the sarbecoviruses related to SARS-CoV-2,” said co-senior author Simon Dellicour, Ph.D., head of the Spatial Epidemiology Lab at Université Libre de Bruxelles and visiting professor at KU Leuven.

In contrast, the analysis also revealed that the most recent sarbecovirus ancestors of both SARS-CoV-1 and SARS-CoV-2 left their points of origin less than 10 years before they were first reported to infect humans — more than a thousand kilometers away.

“We show that the original SARS-CoV-1 was circulating in Western China — just one to two years before the emergence of SARS in Guangdong Province, South Central China, and SARS-CoV-2 in Western China or Northern Laos — just five to seven years before the emergence of COVID-19 in Wuhan,” said Jonathan E. Pekar, Ph.D., a 2023 graduate of the Bioinformatics and Systems Biology program at UC San Diego School of Medicine, now a  postdoctoral researcher at the University of Edinburgh.

The researchers calculated that given the distances that SARS-CoV-1 and SARS-CoV-2 would have had to cover so quickly, it is highly improbable that they could have been carried there via bat dispersal. Much more likely: they were transported there accidentally by wild animal traders via intermediate hosts.

In fact, previous studies have suggested that SARS-CoV-1 was likely carried from Yunnan Province in Western China to Guangdong Province by infected palm civets or raccoon dogs — animals commonly traded for their fur and meat. However, the current study provides the strongest evidence to date that SARS-CoV-2 made it to humans in a similar manner.

“The viruses most closely related to the original SARS coronavirus were found in palm civets and raccoon dogs in southern China, hundreds of miles from the bat populations that were their original source,” said co-senior author Michael Worobey, Ph.D., professor and head of the Department of Ecology and Evolutionary Biology at The University of Arizona. For more than two decades the scientific community has concluded that the live-wildlife trade was how those hundreds of miles were covered. We’re seeing exactly the same pattern with SARS-CoV-2.”

The findings dispute a widely circulated idea that SARS-CoV-1 emerged naturally, but SARS-CoV2 was the result of a lab leak.

“At the outset of the COVID-19 pandemic, there was a concern that the distance between Wuhan and the bat virus reservoir was too extreme for a zoonotic origin,” Wertheim said. “This paper shows that it isn’t unusual and is, in fact, extremely similar to the emergence of SARS-CoV-1 in 2002.”

Zoonotic spillover events are on the rise worldwide due to an increase in human-animal interactions via the wildlife trade, as well as urbanization and habitat destruction. The researchers believe that by continuing to sample wild bat populations for sarbecoviruses, it may be possible to discover where the next coronavirus pandemic will come from. What’s more, understanding the evolutionary history of these viruses and other pathogens can help us prepare for and control future disease outbreaks.