RT Journal Article
SR Electronic
T1 Impaired cytotoxic CD8+ T cell response in elderly COVID-19 patients
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.08.21.262329
DO 10.1101/2020.08.21.262329
A1 Jaana Westmeier
A1 Krystallenia Paniskaki
A1 Zehra Karaköse
A1 Tanja Werner
A1 Kathrin Sutter
A1 Sebastian Dolff
A1 Marvin Overbeck
A1 Andreas Limmer
A1 Jia Liu
A1 Xin Zheng
A1 Thorsten Brenner
A1 Marc M. Berger
A1 Oliver Witzke
A1 Mirko Trilling
A1 Mengji Lu
A1 Dongliang Yang
A1 Nina Babel
A1 Timm Westhoff
A1 Ulf Dittmer
A1 Gennadiy Zelinskyy
YR 2020
UL http://biorxiv.org/content/early/2020/08/24/2020.08.21.262329.abstract
AB 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.