Cellular immune signatures associated with fast versus slow clearance of infectious SARS-CoV-2 4227

Abstract Description The reasons for varied SARS-CoV-2 transmission risk among infected individuals remain unclear. In this study, we identify cellular immune signatures associated with the speed of viral clearance in individuals with acute SARS-CoV-2 infection. We utilized mass cytometry (CyTOF) on peripheral blood mononuclear cells (PBMCs) from 34 vaccinated and unvaccinated individuals sampled during acute SARS-CoV-2 infection (4-6 days post-symptom onset), with uninfected controls for comparison (n = 5). Amongst unvaccinated participants, greater activation of non-naïve CD8+ T cells, plasmablasts, Th1 CD4+ T cells, and γδ T cells correlated significantly with faster viral clearance (Spearman’s p_adj < 0.05). In addition, coordinated activation between 297 pairs of innate and/or adaptive immune cell features was observed uniquely in infected and not in uninfected individuals (Spearman’s p_adj < 0.05, r > |0.65|). Finally, vaccinated individuals had a cellular immune signature during acute SARS-CoV-2 infection that was similar to uninfected participants, and showed significantly less immune activation across broad cell types (T/B/NK cells and monocytes) compared to unvaccinated individuals with similar duration of viral shedding (p_adj < 0.05, Kruskal-Wallis test). Our findings provide crucial insight into early immune signatures associated with the speed of clearance of infectious SARS-CoV-2 and could inform future vaccine strategies and therapeutic approaches to reduce transmission. Funding Sources Supported by the Centers for Disease Control and Prevention Broad Agency Announcement (contract 75D30120C08009) Topic Categories Viral Immunology (VIR)