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?:abstract
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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 IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in 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 than in younger patients
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