A possible role of immunopathogenesis in COVID-19 progression

BackgroundThe role of cellular immunity in pathogenesis of COVID-19 is unclear and conflicting data points to insufficient or pathogenic immunity as drivers of COVID-19 progression. Here we aimed to delineate the phenotype and function of the immune system in patients with moderate, severe, and critical COVID-19. MethodsIn this prospective study, we included 53 patients with moderate (n=21), severe (n=18), and critical (n=14) COVID-19 manifestations. Using multiparametric flow cytometry we compared quantitative, phenotypic, and functional characteristics of circulating immune cells, SARS-CoV-2 antigen-reactive T-cells, and humoral immunity. ResultsDeep phenotypic profiling revealed a depletion of circulating bulk CD8+ T-cells, CD4+ and CD8+ T-cell subsets with activated memory/effector T-cells expressing CD57+, HLA-DR+, and the key activation and migration molecule CD11a++ in critical COVID-19. Importantly, survival from acute respiratory distress syndrome was accompanied by a recovery of the depleted CD11++ T-cell subsets including T-cells expressing CD28, CD57, HLA-DR activation/effector molecules. We further observed a stronger response of S-protein specific T-cells producing inflammatory cytokines in critical COVID-19 cases. This seemingly contradictory observation is in fact confirmation of the underlying immunopathogenesis in patients with critical COVID-19. ConclusionOur findings suggest a CD11a-based immune signature as a possible prognostic marker for disease development. Our data further reveal that increased rather than decreased SARS-CoV-2 specific T cell immunity is associated with adverse outcome in COVID-19. Tissue migration of activated effectors T-cells may constitute a crucial cornerstone in the immunopathogenesis of SARS-CoV-2 associated tissue injury. Trial registrationThis is a prospective observational study without a trial registration number. FundingThis work was supported by grants from Mercator Foundation, the BMBF e:KID (01ZX1612A), and BMBF NoChro (FKZ 13GW0338B). 25 Word summaryStronger S-protein reactivity and decreased frequency of activated memory/effector T-cells expressing CD11a++ suggests immunopathogenesis in critical COVID-19 mediated by tissue migration of activated effector T-cells.