ABSTRACT
Recent common coronavirus (CCV) infections are associated with reduced COVID-19 severity upon SARS-CoV-2 infection, however the immunological mechanisms involved are unknown. We completed serological assays using samples collected from health care workers to identify antibody types associated with SARS-CoV-2 protection and COVID-19 severity. Rare SARS-CoV-2 cross-reactive antibodies elicited by past CCV infections were not associated with protection; however, the duration of symptoms following SARS-CoV-2 infections was significantly reduced in individuals with higher common betacoronavirus ({beta}CoV) antibody titers. Since antibody titers decline over time after CCV infections, individuals in our cohort with higher {beta}CoV antibody titers were more likely recently infected with common {beta}CoVs compared to individuals with lower antibody titers. Therefore, our data suggest that recent {beta}CoV infections potentially limit the severity of SARS-CoV-2 infections through mechanisms that do not involve cross-reactive antibodies. Our data are consistent with the emerging hypothesis that cellular immune responses elicited by recent common {beta}CoV infections transiently reduce disease severity following SARS-CoV-2 infections.