Impaired Cytotoxic CD8(+) T Cell Response in Elderly COVID-19 Patients

Westmeier, Jaana; Paniskaki, Krystallenia; Karaköse, Zehra; Werner, Tanja; Sutter, Kathrin; Dolff, Sebastian; Overbeck, Marvin; Limmer, Andreas; Liu, Jia; Zheng, Xin; Brenner, Thorsten; Berger, Marc M.; Witzke, Oliver; Trilling, Mirko; Lu, Mengji; Yang, Dongliang; Babel, Nina; Westhoff, Timm; Dittmer, Ulf; Zelinskyy, Gennadiy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8(+) T cells, but not CD4(+) T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8(+) T cell subsets. PD-1-expressing CD8(+) T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8(+) cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.