White-tailed deer ­– the most abundant large mammal in North America – are harboring SARS-CoV-2 variants that once widely circulated but are no longer found in humans.

Whether or not deer could act as long-term reservoirs for these variants that have become obsolete in people is unknown, as scientists need more time and study to verify if it’s true.

The study, “White-tailed Deer (Odocoileus virginianus) May Serve as a Wildlife Reservoir for Nearly Extinct SARS-CoV-2 Variants of Concern,” which published Jan. 31 in the journal Proceedings of the National Academy of Sciences, represents one of the most comprehensive studies to date to assess the prevalence, genetic diversity and evolution of SARS-CoV-2 in white-tailed deer. The study focused on the white-tailed deer population in New York.

“One of the most striking findings of this study was the detection of co-circulation of three variants of concern – alpha, gamma and delta – in this wild animal population,” said Dr. Diego Diel, associate professor in the Department of Population Medicine and Diagnostic Sciences and director of the Virology Laboratory at the College of Veterinary Medicine’s (CVM) Animal Health Diagnostic Center. 

Over the course of the pandemic, deer have become infected with SARS-CoV-2 through ongoing contact with humans, possibly from hunting, wildlife rehabilitations, feeding of wild animals or through wastewater or water sources, though no one knows for sure.

“A virus that emerged in humans in Asia, most likely after a spillover event from an animal reservoir into humans, apparently, or potentially, has now found a new wildlife reservoir in North America,” Diel said.

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This current study was made possible thanks to a program co-designed by Krysten Schuler, assistant research professor in the ­­Department of Public and Ecosystem Health (CVM) and a senior author on the study.

In her role as director of the Cornell Wildlife Health Lab, Schuler has worked with the New York State Department of Environmental Conservation to design a statewide surveillance program for chronic wasting disease in white-tailed deer. The program collected thousands of samples of deer lymph tissues taken from deer killed by participating hunters.

“We were able to leverage those samples that had already been collected and then test them for SARS-CoV-2, so we had a good statewide representation,” Schuler said.

The 5,700 samples used in the study were collected over two years from 2020-22, and included important information about when and where the samples were collected and each animal’s sex and age.

The testing revealed potential hotspots of infection across the state, including seven clusters where samples from a defined geographic area all contained the same variant. Samples from one cluster, for example, confined to one county, were all positive for the gamma variant. Similar clusters were also found for alpha and delta variants in different locations in the state.

When the researchers compared the genomic sequences of the variants found in deer with sequences of the same variants taken from humans across New York, they found the viruses had mutated in the deer, suggesting the variants had likely been circulating in deer for many months. By the time alpha and gamma variants were detected in deer, for example, there was no evidence of these viral strains were still circulating in humans. In fact,  when they were found in deer, neither variant had been detected in humans in New York for four to six months.

“When we did sequence comparisons between those viruses recovered from white-tailed deer with the human sequences, we observed a significant number of mutations across the virus genome,” Diel said, adding that some of the viruses had up to 80 mutations compared with the human sequences, providing further evidence that the viruses had likely been circulating in the deer for some time. The mutations suggest the virus has adapted to deer, possibly making it more transmissible between them.

In future work, Diel and colleagues hope to assess the effect of those mutations, including whether these changes make the virus more or less capable of binding to human receptors, information that could predict the possibility of spill back to humans from mutant variants. Currently, only one study published in Canada has documented a case of a human being infected by SARS-CoV-2 that originated in deer.   

“Obviously, humans are still the primary reservoir and the likelihood of anybody getting SARS-CoV-2 is from another human rather than a deer,” Schuler said.

More study is needed to confirm whether white-tailed deer have truly become a reservoir for these variants extinct now in humans or whether they will disappear over time in the wild. Other questions include whether the deer might spread SARS-CoV-2 to other wildlife, including predators.  

“Because of the evidence obtained in our study, it is very important to continue to monitor the virus in these animal populations to really understand and track changes that could lead or favor spill back into humans and other wildlife,” Diel said.

There are an estimated 30 million white-tailed deer in the United States. A 2022 study by Diel and others found that across five states surveyed in 2021, SARS-CoV-2 was found in up to 40% of white-tailed deer.