Population-matched IGHV antibody haplotypes and their role in COVID-19 outcomes 4236

Abstract Description The COVID-19 pandemic caused widespread devastation, disproportionately affecting minority populations in the United States with severe and long COVID-19 symptoms. A neutralizing antibody response is critical for clearing SARS-CoV-2; however, the influence of antibody haplotypes on these responses remains largely underexplored. To address this, we utilized the IReceptor database to analyze antibody repertoires, specifically focusing on CDRH3 regions in six major demographics: Asian, Black, Black British, Caucasian, Latin, and Southeast Asian populations. Our investigation centered on unique and public antibody responses, including analyses of IGHV gene usage, CDRH3 composition, and structural features. We identified demographic-specific IGHV gene usages that strongly correlated with favorable prognoses. Moreover, several CDRH3 sequences associated with good prognoses were structurally similar to those of known neutralizing monoclonal antibodies, underscoring their potential role in effective immune responses. These findings emphasize the critical need for integrating antibody haplotyping into a clinical prognostic tool to enhance personalized treatment strategies for COVID-19 and future viral outbreaks. By demonstrating the influence of antibody haplotype on immune responses, this study highlights the potential for repertoire-based insights to bridge health disparities. Funding Sources This project was supported by grants from the National Institutes of Health (NIH), National Institute of General Medical Sciences (NIGMS), IDeA Networks of Biomedical Research Excellence (INBRE), Award number: P20GM103466. The content is solely the authors’ responsibility and does not necessarily represent the official views of the National Institutes of Health. Topic Categories Computational and Systems Immunology (COMP)