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

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.