Integrative Single-Cell Epigenomic Landscape of Precision Immune Profiling Shows Memory Formation and Trained Immunity in COVID-19 convalescent individuals

Infection with the SARS-CoV-2 viruses often causes severe complications and even death for some individuals, and yet others are asymptomatic, thus presenting a puzzle as to how immune responses differ among people. Here, we performed in-depth epigenomic and TCR analysis on peripheral blood mononuclear cells of COVID-19 convalescent individuals. We identified sequential epigenomic states as TBET-enriched activated lineage clusters in CD16+ monocytes, B cells and CD8+ T cells and IRF1-enriched trained and activated CD14+ monocytes. Comparing cis and trans regulators also revealed that viral infection induces an accelerated IgG class switch recombination. Analysis of single-cell TCR clonality with the chromatin accessibility landscape revealed expansion of putative SARS-CoV-2 specific CD8+ T cell with epigenomic profiles that promotes either effector or memory cell differentiation. Overall, our data suggested that COVID-19 convalescent individuals established immunologic memory through global remodeling of the chromatin accessibility landscape.