Humans have infected a wide range of animals with SARS-CoV-2 viruses1–5, but the establishment of a new natural animal reservoir has not been observed. Here, we document that free-ranging white-tailed deer (Odocoileus virginianus) are highly susceptible to infection with SARS-CoV-2 virus, are exposed to a range of viral diversity from humans, and are capable of sustaining transmission in nature. SARS-CoV-2 virus was detected by rRT-PCR in more than one-third (129/360, 35.8%) of nasal swabs obtained from Odocoileus virginianus in northeast Ohio (USA) during January-March 2021. Deer in 6 locations were infected with 3 SARS-CoV-2 lineages (B.1.2, B.1.582, B.1.596). The B.1.2 viruses, dominant in humans in Ohio at the time, infected deer in four locations. Probable deer-to-deer transmission of B.1.2, B.1.582, and B.1.596 viruses was observed, allowing the virus to acquire amino acid substitutions in the spike protein (including the receptor-binding domain) and ORF1 that are infrequently seen in humans. No spillback to humans was observed, but these findings demonstrate that SARS-CoV-2 viruses have the capacity to transmit in US wildlife, potentially opening new pathways for evolution. There is an urgent need to establish comprehensive “One Health” programs to monitor deer, the environment, and other wildlife hosts globally.
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