The diversity of influenza A viruses (IAV) is primarily hosted by two highly divergent avian orders: Anseriformes (ducks, swans and geese) and Charadriiformes (gulls, terns and shorebirds). Studies of IAV have historically focused on Anseriformes, specifically dabbling ducks, overlooking the diversity of hosts in nature, including gull and goose species that have successfully adapted to human habitats. This study sought to address this imbalance by characterizing spillover dynamics and global transmission patterns of IAV over 10 years at greater taxonomic resolution than previously considered. Furthermore, the circulation of viral subtypes in birds that are either host-adapted (low pathogenic H13, H16) or host-generalist (highly pathogenic avian influenza—HPAI H5) provided a unique opportunity to test and extend models of viral evolution. Using Bayesian phylodynamic modelling we uncovered a complex transmission network that relied on ecologically divergent bird hosts. The generalist subtype, HPAI H5 was driven largely by wild geese and swans that acted as a source for wild ducks, gulls, land birds, and domestic geese. Gulls were responsible for moving HPAI H5 more rapidly than any other host, a finding that may reflect their long-distance, pelagic movements and their immuno-naïve status against this subtype. Wild ducks, long viewed as primary hosts for spillover, occupied an optimal space for viral transmission, contributing to geographic expansion and rapid dispersal of HPAI H5. Evidence of inter-hemispheric dispersal via both the Pacific and Atlantic Rims was detected, supporting surveillance at high latitudes along continental margins to achieve early detection. Both neutral (geographic expansion) and non-neutral (antigenic selection) evolutionary processes were found to shape subtype evolution which manifested as unique geographic hotspots for each subtype at the global scale. This study reveals how a diversity of avian hosts contribute to viral spread and spillover with the potential to improve surveillance in an era of rapid global change.

Ferrets (Mustela putorius furo) are mustelids of special relevance to laboratory studies of respiratory viruses and have been shown to be susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and onward transmission. Here, we report the results of a natural experiment where 29 ferrets in one home had prolonged, direct contact and constant environmental exposure to two humans with symptomatic disease, one of whom was confirmed positive for SARS-CoV-2. We observed no evidence of SARS-CoV-2 transmission from humans to ferrets based on viral and antibody assays. To better understand this discrepancy in experimental and natural infection in ferrets, we compared SARS-CoV-2 sequences from natural and experimental mustelid infections and identified two surface glycoprotein Spike (S) mutations associated with mustelids. While we found evidence that angiotensin-converting enzyme II provides a weak host barrier, one mutation only seen in ferrets is located in the novel S1/S2 cleavage site and is computationally predicted to decrease furin cleavage efficiency. These data support the idea that host factors interacting with the novel S1/S2 cleavage site may be a barrier in ferret SARS-CoV-2 susceptibility and that domestic ferrets are at low risk of natural infection from currently circulating SARS-CoV-2. We propose two mechanistically grounded hypotheses for mustelid host adaptation of SARS-CoV-2, with possible effects that require additional investigation. Significance Ferrets have been demonstrated to be susceptible to laboratory infection of SARS-CoV-2, raising the possibility of natural transmission from humans into their pets in domestic settings. We demonstrate that ferrets may have host barriers that limit natural infection and transmission. First, we find no evidence of infection in 29 ferrets from a home with constant exposure to two adults with one confirmed and one suspected case of symptomatic COVID-19. Second, we analyze genetic sequences from viruses and hosts and demonstrate that ferrets have genetic factors that confer resistance to natural SARS-CoV-2 infection. These data suggest that ferret infection may require viral adaptation, and therefore ferrets may only be semipermissive models of SARS-CoV-2 disease or transmission.

Natural infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been documented in over 60 animal species, some distantly related. Several marine mammals have been predicted as highly susceptible to SARS-CoV-2 infection based on the homology of their ACE2 receptors to those of humans. To assess potential exposure of marine mammals to SARS-CoV-2, we conducted an opportunistic survey from 2020 to 2025 and tested 1,808 swabs and 378 serum samples from 21 marine mammal species in the United States. All the swabs tested by RT-qPCR were negative, indicating the absence of active infection. A low level of SARS-CoV-2 neutralizing antibodies was detected in three pinniped species, including Phoca vitulina (harbor seal, 13.6%, 95% CI: 5.2–27.4%), Zalophus californianus (California sea lion, 7%, 95% CI: 1.9–17.0%), and Halichoerus grypus (grey seal, 3.7%, 95% CI: 0.5–12.7%). These findings represent the first serological evidence of SARS-CoV-2 exposure in marine mammals in the United States, highlighting the need for continued monitoring of these populations and further research on SARS-CoV-2 transmission dynamics in wildlife.

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a wide range of animal species, including wildlife. Although SARS-CoV-2 infection has been widely reported in wildlife, particularly in white-tailed deer (WTD; Odocoileus virginianus) across the United States, data on viral circulation in New England wildlife remain limited. Here, we investigated active SARS-CoV-2 infection and serological evidence of previous exposure in free-ranging wildlife from New England and Virginia. We examined samples from 1646 animals representing 29 wildlife species, collected through wildlife rehabilitation centers, clinics, and hunter harvests in New England and Virginia between 2022 and 2025. SARS-CoV-2 RNA was detected in three WTD from Massachusetts and Vermont. Phylogeographic analysis showed that the Vermont WTD SARS-CoV-2 sequences were closely related to contemporaneous human SARS-CoV-2 sequences from the same region, consistent with a possible human-to-deer spillover event. Serological screening by ELISA detected SARS-CoV-2 reactive samples in nine individuals from three species, including Eastern cottontail (Sylvilagus floridanus), Eastern coyote (Canis latrans), and raccoon (Procyon lotor), providing putative evidence of prior SARS-CoV-2 exposure. However, neutralizing antibodies against the SARS-CoV-2 Omicron variant were detected in only a single Eastern cottontail. Overall, these findings indicate sporadic SARS-CoV-2 detection and limited serological evidence of prior exposure among wildlife sampled in New England and Virginia, and highlight the importance of continued surveillance to detect spillover events, monitor viral evolution, and assess the potential risks associated with wildlife reservoirs.

Since its emergence in 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected a wide range of animal species, including wildlife. Although SARS-CoV-2 infection has been widely reported in wildlife, particularly in white-tailed deer (WTD; Odocoileus virginianus) across the United States, data on viral circulation in New England wildlife remain limited. Here, we evaluated SARS-CoV-2 infection and serological evidence of previous exposure in free-ranging wildlife from the northeastern United States. We examined samples from 1,646 animals representing 28 wildlife species, collected through wildlife rehabilitation centers, clinics, and hunter harvests in New England and Virginia between 2022 and 2025. SARS-CoV-2 RNA was detected in three WTD from Massachusetts and Vermont. Phylogeographic analysis of Vermont WTD sequences indicated a human SARS-CoV-2 lineage as the most likely source, consistent with a single human-to-deer spillover event followed by subsequent circulation within deer. Serological screening using ELISA detected SARS-CoV-2 antibodies in 12 individ-uals from three species, including Eastern cottontail (Sylvilagus floridanus), Eastern coyote (Canis latrans), and raccoon (Procyon lotor), although neutralizing antibodies were found in only one Eastern cottontail. Overall, these findings reveal ongoing but limited SARS-CoV-2 circulation in northeastern wildlife and highlight the importance of continued surveillance to detect spillover events, monitor viral evolution, and evaluate potential risks posed by wildlife.