Phenotype of SARS-CoV-2-specific T-cells in COVID-19 patients with acute respiratory distress syndrome

Daniela Weiskopf; Katharina S. Schmitz; Matthijs P. Raadsen; Alba Grifoni; Nisreen M.A. Okba; Henrik Endeman; Johannes P.C. van den Akker; Richard Molenkamp; Marion P.G. Koopmans; Eric C.M. van Gorp; Bart L. Haagmans; Rik L. de Swart; Alessandro Sette; Rory Dylan de Vries

Collectively, these data provide information on the breadth, kinetics and phenotype of virus-specific cellular immune responses in COVID-19 ARDS patients. We provide evidence that SARS-CoV-2-specific CD4 + and CD8 + T-cells appear in blood of ARDS patients in the first two weeks post onset of symptoms, and their frequency increases over time. The phenotype of the antigen-specific cellular immune response is balanced; SARS-CoV-2-specific CD4 + T-cells in blood were typically central memory, CD8 + T-cells typically had a more effector phenotype. It is tempting to speculate that the CD8 + cytotoxic T-cells are predominantly responsible for the production of IFNg, whereas virus-specific CD4 + T-cells could be responsible for the production of typical Th1 and Th2 cytokines. Elevated levels of IL-6 in patient plasma have previously been correlated to respiratory failure in COVID-19 patients 11 . Here, we could not detect increased specific production of IL-6 in PBMC stimulated with peptide pools, suggesting that virus-specific T-cells are not to blame for the production of IL-6 and the concomitant 'cytokine storm', but that these are predominantly mediated by innate immune cells.