TY - JOUR T1 - Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients JF - bioRxiv DO - 10.1101/2020.08.21.262329 SP - 2020.08.21.262329 AU - Jaana Westmeier AU - Krystallenia Paniskaki AU - Zehra Karaköse AU - Tanja Werner AU - Kathrin Sutter AU - Sebastian Dolff AU - Marvin Overbeck AU - Andreas Limmer AU - Jia Liu AU - Xin Zheng AU - Thorsten Brenner AU - Marc M. Berger AU - Oliver Witzke AU - Mirko Trilling AU - Mengji Lu AU - Dongliang Yang AU - Nina Babel AU - Timm Westhoff AU - Ulf Dittmer AU - Gennadiy Zelinskyy Y1 - 2020/01/01 UR - http://biorxiv.org/content/early/2020/08/24/2020.08.21.262329.abstract N2 - 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 provides valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.Importance Cytotoxic T cells are responsible for the elimination of infected cells and are key players for the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group in comparison to younger patients. ER -