New details about the genetics of severe COVID-19 are reported in Nature Genetics this week. Recent genome-wide association studies have uncovered a series of genetic variants in distinct loci that are associated with susceptibility to SARS-CoV-2 infection, including the chr12q24.13 locus encoding OAS1–OAS3 antiviral proteins. To gain better insights into this locus, a National Cancer Institute-led team analyzed data on hospitalized versus non-hospitalized COVID-19 patients of European and African ancestries, finding that the risk of hospitalization was associated with a common OAS1 haplotype comprised of derived human-specific risk alleles of two OAS1 variants. The investigators also provide evidence for the combined functional contribution of these variants on the expression of OAS1, an antiviral protein critical for SARS-CoV-2 clearance. "Thus, genetically regulated OAS1 expression contributes to association with SARS-CoV-2 clearance and risk of hospitalization for COVID-19," they write. The study's authors also note that SARS-CoV-2 expression decreased in cells treated with interferons, suggesting that such treatment may prove beneficial for patients with the OAS1 risk haplotype.