Dynamics of Anti-ABO(H) Antibody Expression in SARS-CoV-2-Infected Patients

Abstract The association between ABO(H) blood groups and COVID-19 susceptibility and severity has been studied throughout the pandemic. However, the comprehensively tracked dynamic changes of antibodies to ABO(H) over the course of COVID-19 infection remain poorly characterized. Here, we present a longitudinal cohort study that tracked changes in anti-ABO(H) antibody levels and isotypes in serum of 65 COVID-19 patients. Sera were collected at (1) time of hospital admission, (2) 2–3 weeks after symptom onset, and (3) just before hospital discharge or death. Anti-ABO(H) glycan-specific IgG, IgM, and IgA isotypes were profiled using high-throughput Luminex assays, employing beads derivatized with glycans representing the major ABO(H) antigens. While each patient demonstrated unique repertoires of anti-ABO(H) antibodies, unexpected changes in isotypes were observed, indicating varied impact on naturally occurring antibody levels following SARS-CoV-2 infection. Interestingly, blood group O patients showed a higher likelihood of possessing anti-ABO(H) IgA than other blood types. Additionally, we identified autoantibodies against non-blood-group self-glycans in a small proportion of the cohort. Data suggest that exposure to virus represents an underappreciated factor influencing anti-ABO(H) antibody profiles. These results provide a deeper understanding of the potential interplay between anti-ABO(H) antibodies and progression of SARS-CoV-2 infection.