Within-host genetic diversity of SARS-CoV-2 across animal species

Infectious disease transmission to different host species makes eradication very challenging and expands the diversity of evolutionary trajectories taken by the pathogen. Since the beginning of the ongoing COVID-19 pandemic, SARS-CoV-2 has been transmitted from humans to many different animal species, in which viral variants of concern could potentially evolve. Previously, using available whole genome consensus sequences of SARS-CoV-2 from four commonly sampled animals (mink, deer, cat, and dog), we inferred similar numbers of transmission events from humans to each animal species. Using a genome-wide association study, we identified 26 single nucleotide variants (SNVs) that tend to occur in deer-more than any other animal-suggesting a high rate of viral adaptation to deer. The reasons for this rapid adaptive evolution remain unclear, but within-host evolution-the ultimate source of the viral diversity that transmits globally-could provide clues. Here, we quantify intra-host SARS-CoV-2 genetic diversity across animal species and show that deer harbor more intra-host SNVs (iSNVs) than other animals, providing a larger pool of genetic diversity for natural selection to act upon. Mixed infections involving more than one viral lineage are unlikely to explain the higher diversity within deer. Rather, a combination of higher mutation rates, longer infections, and species-specific selective pressures are likely explanations. Combined with extensive deer-to-deer transmission, the high levels of within-deer viral diversity help explain the apparent rapid adaptation of SARS-CoV-2 to deer.