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Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients.
mBio. 2020 09 18; 11(5)MBIO

Abstract

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.

Authors+Show Affiliations

Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany. Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany. Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum, Germany.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de. Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32948688

Citation

Westmeier, Jaana, et al. "Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients." MBio, vol. 11, no. 5, 2020.
Westmeier J, Paniskaki K, Karaköse Z, et al. Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients. mBio. 2020;11(5).
Westmeier, J., Paniskaki, K., Karaköse, Z., Werner, T., Sutter, K., Dolff, S., Overbeck, M., Limmer, A., Liu, J., Zheng, X., Brenner, T., Berger, M. M., Witzke, O., Trilling, M., Lu, M., Yang, D., Babel, N., Westhoff, T., Dittmer, U., & Zelinskyy, G. (2020). Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients. MBio, 11(5). https://doi.org/10.1128/mBio.02243-20
Westmeier J, et al. Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients. mBio. 2020 09 18;11(5) PubMed PMID: 32948688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients. AU - Westmeier,Jaana, AU - Paniskaki,Krystallenia, AU - Karaköse,Zehra, AU - Werner,Tanja, AU - Sutter,Kathrin, AU - Dolff,Sebastian, AU - Overbeck,Marvin, AU - Limmer,Andreas, AU - Liu,Jia, AU - Zheng,Xin, AU - Brenner,Thorsten, AU - Berger,Marc M, AU - Witzke,Oliver, AU - Trilling,Mirko, AU - Lu,Mengji, AU - Yang,Dongliang, AU - Babel,Nina, AU - Westhoff,Timm, AU - Dittmer,Ulf, AU - Zelinskyy,Gennadiy, Y1 - 2020/09/18/ PY - 2020/9/19/entrez PY - 2020/9/20/pubmed PY - 2020/10/6/medline KW - CD4+ KW - CD8+ KW - COVID-19 KW - PD-1 KW - SARS-CoV-2 KW - aging KW - cytotoxic T cells KW - granzyme KW - perforin JF - mBio JO - mBio VL - 11 IS - 5 N2 - 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. SN - 2150-7511 UR - https://www.unboundmedicine.com/medline/citation/32948688/Impaired_Cytotoxic_CD8+_T_Cell_Response_in_Elderly_COVID_19_Patients_ L2 - http://mbio.asm.org/cgi/pmidlookup?view=long&pmid=32948688 DB - PRIME DP - Unbound Medicine ER -