SARS-CoV-2 Delta variant re-emerges in US farmed mink and free-ranging white-tailed deer in 2022–2023

American mink (Neogale vison) are susceptible to SARS-CoV-2, but little is known about virus circulation in mink since 2021. Here, in the first active surveillance study of SARS-CoV-2 in apparently healthy farmed mink in the United States, we find a ~0.9% (760/85,656) RT-PCR positivity rate among nasal swabs collected in 18 farms across six states during 2022–2023. Phylogenetic analysis of 293 viral genome sequences shows that human-adapted SARS-CoV-2 variants (e.g., Omicron) repeatedly spill over into mink. Surprisingly, the detection of a Delta lineage virus (AY.39) on a mink farm four months after its last detection in humans within the same state suggests prolonged unsampled transmission. The spread of mink-adapted AY.39 viruses from a mink farm to neighboring free-ranging white-tailed deer represents a rare instance of SARS-CoV-2 transmission between livestock and wildlife. These findings demonstrate the value of active surveillance for identifying subclinical infections and interspecies transmission between humans, mink, and wildlife. American mink are known to be susceptible to SARS-CoV-2, yet the extent of virus circulation in these animals remains unclear. Here, the authors conduct an active surveillance of asymptomatic US farmed mink, revealing mink-adapted variants and interspecies transmission, underscoring the importance of monitoring for subclinical infections and cross-species spread.