TCR signatures following SARS-CoV-2 infection correlate with clinical symptoms and post-acute sequelae of COVID-19

Abstract

Abstract T cell receptor (TCR) diversity analysis is critical for understanding the complex role of T cells in disease pathogenesis. In this study we profile the CD4+ and CD8+ T cell compartments in SARS-CoV-2-recovered participants and use TCR beta variable (TRBV) receptor deep sequencing to explore the association between the T cell repertoire and severity of COVID-19. We compare mild and severe COVID-19 cohorts and identify two unique populations of shared TRBV sequences that are significantly enriched in patients following severe disease or in patients with post-acute sequelae of COVID-19 (PASC). These enriched TRBV sequences display a clear association with human leukocyte antigen (HLA) class I and class II alleles, yet are distinct from the SARS-CoV-2-specific T cell repertoire. Exploration of additional disease datasets confirms that these TRBV populations are present in unexposed individuals and potentially represent a TRBV signature associated with either restricting efficient viral control or exacerbating disease symptoms. Subject terms: COVID-19, T cell immunity, T cell receptor