High levels of SARS-CoV-2 specific T-cells with restricted functionality in patients with severe course of COVID-19

Schub, David; Klemis, Verena; Schneitler, Sophie; Mihm, Janine; Lepper, Philipp M; Wilkens, Heinrike; Bals, Robert; Eichler, Hermann; Gaertner, Barbara C; Becker, Soeren L; Sester, Urban; Sester, Martina; Schmidt, Tina

Patients infected with SARS-CoV-2 differ in the severity of disease. In this study, SARS-CoV-2 specific T-cells and antibodies were characterized in patients with different COVID-19 related disease severity. Despite severe lymphopenia affecting all major lymphocyte subpopulations, patients with severe disease mounted significantly higher levels of SARS-CoV-2 specific T-cells as compared to convalescent individuals. SARS-CoV-2 specific CD4 T-cells dominated over CD8 T-cells and closely correlated with the number of plasmablasts and SARS-CoV-2 specific IgA- and IgG-levels. Unlike in convalescents, SARS-CoV-2 specific T-cells in patients with severe disease showed marked alterations in phenotypical and functional properties, which also extended to CD4 and CD8 T-cells in general. Given the strong induction of specific immunity to control viral replication in patients with severe disease, the functionally altered phenotype may result from the need for contraction of specific and general immunity to counteract excessive immunopathology in the lung.