Minimal Impact of Prior Common Cold Coronavirus Exposure on Immune Responses to Severe Acute Respiratory Syndrome Coronavirus 2 Vaccination or Infection Risk in Older Adults in Congregate Care

Background: Common cold coronaviruses were a frequent cause of respiratory infections in older adults living in congregate care homes before the coronavirus disease 2019 pandemic, which may influence immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and infection. We investigated humoral and cellular immune responses to prior common cold coronaviruses and SARS-CoV-2, how they are affected by SARS-CoV-2 vaccination and infection, and their associations with Omicron BA.1 SARS-CoV-2 infections in residents of long-term care and retirement homes. Methods: In SARS-CoV-2 infection-naive residents with 3 monovalent messenger RNA SARS-CoV-2 vaccinations, we measured serum anti-receptor binding domain (RBD) immunoglobulin (Ig) G and IgA antibody titers against SARS-CoV-2 and common cold human coronavirus (HCoV) NL63, HCoV-OC43, and HCoV-229E; ancestral and Omicron BA.1 neutralizing antibodies; and CD4⁺ and CD8⁺ T-cell activation responses to membrane, nucleocapsid, and spike proteins. We examined the relationships of common cold coronavirus and SARS-CoV-2 humoral immune responses, whether antibody and T-cell responses changed after SARS-CoV-2 messenger RNA vaccination or infection, and their associations with Omicron BA.1 infection. Results: Anti-RBD IgG HCoV-OC43 titers were positively correlated with SARS-CoV-2 anti-RBD IgG and neutralizing antibody titers. Common cold coronavirus anti-RBD IgA titers, but not anti-RBD IgG titers, increased after SARS-CoV-2 vaccination or infection, and many residents had cross-reactive T cells. Common cold coronavirus humoral immunity was similar in residents without and those with subsequent Omicron BA.1 infection. Conclusions: Despite frequent exposure, and associations of common cold coronavirus and vaccine-induced SARS-CoV-2 humoral immunity, preexisting common cold coronavirus immunity was not associated with Omicron BA.1 infection in residents of long-term care and retirement communities.