Recent pandemic viruses, including SAR-CoV-2, spread directly to people without adaptation, researchers say

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Contrary to prevailing belief, an evolutionary analysis finds no evidence that most viruses with epidemic or pandemic potential that jumped from animals to people were shaped by selection in a lab or prolonged evolution in an intermediate host—challenging claims that SARS-CoV-2, the virus that causes COVID-19, was engineered in a lab.

A University of California (UC) San Diego–led research team analyzed viral genomes to characterize natural selection under the hypothesis that zoonotic viruses (Ebola, Marburg, mpox, influenza A, and SARS-CoV-2) need to adapt before infecting people and achieving sustained human-to-human spread. They focused on the evolutionary period right before outbreaks, when viruses would be expected to leave detectable traces of any substantial adaptation.

The researchers validated their approach using known examples of artificially selected viruses grown in cell culture or lab animals, which showed clear and reproducible evolutionary footprints distinct from natural transmission.

The findings were published late last week in Cell.

1977 reemergence of H1N1 flu likely a lab accident

The investigators uncovered no evidence of a change in selection intensity right before viral outbreaks in humans compared with typical selection within reservoir hosts. Rather, measurable changes in selection usually appeared only after the virus sustained transmission in people.

The analysis did identify a change in selection on SARS-CoV—which causes SARS (severe acute respiratory syndrome)—in an intermediate host (palm civets) and, in the case of the 1977 reemergence of H1N1 influenza A virus after 20 years of extinction, they detected a preceding shift in selection intensity (accelerated genetic gain), consistent with passage in a lab. Passage is repeated transfer of a virus from one host environment, such as cell culture, egg, or animal, to another to grow, maintain, or study it.

“The 1977 influenza story is, in many ways, even more compelling than what we found for COVID-19,” senior author Joel Wertheim, PhD, of UC San Diego School of Medicine, said in a university news release. “Our results provide new molecular evidence supporting the long-suspected idea that the H1N1 pandemic was sparked by a laboratory strain—possibly in the context of a failed vaccine trial.”

From an evolutionary perspective, we find no evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence.

Joel Wertheim, PhD

The findings are also relevant to the ongoing controversy about the origins of COVID-19.

“From an evolutionary perspective, we find no evidence that SARS-CoV-2 was shaped by selection in a laboratory or prolonged evolution in an intermediate host prior to its emergence,” he said. “That absence of evidence is exactly what we would expect from a natural zoonotic event—and it represents another nail in the coffin for theories invoking laboratory manipulation.”

Human exposure to array of animal viruses matters most

Establishing what natural zoonotic emergence looks like at the genomic level provides a benchmark for distinguishing natural spillovers from lab mishandling or prolonged artificial selection, the authors said.

We conclude that extensive pre-zoonotic adaptation is not necessary for human-to-human transmission of zoonotic viruses.

“We conclude that extensive pre-zoonotic adaptation is not necessary for human-to-human transmission of zoonotic viruses,” they wrote. “Holistic phylogenetic analysis of selection regimes can be used to detect evolutionary signals of host switching or laboratory passage, providing insight into the circumstances of past and future viral emergence.

Wertheim said the findings challenge the idea that pandemic viruses must be evolutionarily special before they jump to people. “Rather than requiring rare, finely tuned adaptations in animals, many viruses may already possess the basic capacity to infect and transmit between humans,” he said. “What matters most is human exposure to a diverse array of animal viruses.”

He added that the team’s goal is not just to understand the past, but to better prepare for the future: “By clarifying how pandemics actually begin, we can focus attention where it belongs—on surveillance, prevention and reducing the opportunities for the constant barrage of viral spillover.”