Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients.
Identifieur interne : 000495 ( Main/Exploration ); précédent : 000494; suivant : 000496Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients.
Auteurs : Jaana Westmeier [Allemagne] ; Krystallenia Paniskaki [Allemagne] ; Zehra Karaköse [Allemagne] ; Tanja Werner [Allemagne] ; Kathrin Sutter [Allemagne, République populaire de Chine] ; Sebastian Dolff [Allemagne] ; Marvin Overbeck [Allemagne] ; Andreas Limmer [Allemagne] ; Jia Liu [République populaire de Chine] ; Xin Zheng [République populaire de Chine] ; Thorsten Brenner [Allemagne] ; Marc M. Berger [Allemagne] ; Oliver Witzke [Allemagne] ; Mirko Trilling [Allemagne, République populaire de Chine] ; Mengji Lu [Allemagne, République populaire de Chine] ; Dongliang Yang [République populaire de Chine] ; Nina Babel [Allemagne] ; Timm Westhoff [Allemagne] ; Ulf Dittmer [Allemagne, République populaire de Chine] ; Gennadiy Zelinskyy [Allemagne, République populaire de Chine]Source :
- mBio [ 2150-7511 ] ; 2020.
Descripteurs français
- KwdFr :
- Adulte d'âge moyen (MeSH), Antigènes CD (métabolisme), Betacoronavirus (pathogénicité), Cytotoxines (métabolisme), Femelle (MeSH), Humains (MeSH), Immunité cellulaire (MeSH), Infections à coronavirus (immunologie), Lymphocytes T CD4+ (anatomopathologie), Lymphocytes T CD4+ (immunologie), Lymphocytes T CD8+ (anatomopathologie), Lymphocytes T CD8+ (immunologie), Lymphocytes T cytotoxiques (anatomopathologie), Lymphocytes T cytotoxiques (immunologie), Mâle (MeSH), Pandémies (MeSH), Pneumopathie virale (immunologie), Sous-populations de lymphocytes T (anatomopathologie), Sous-populations de lymphocytes T (immunologie), Sujet âgé de 80 ans ou plus (MeSH).
- MESH :
- anatomopathologie : Lymphocytes T CD4+, Lymphocytes T CD8+, Lymphocytes T cytotoxiques, Sous-populations de lymphocytes T.
- immunologie : Infections à coronavirus, Lymphocytes T CD4+, Lymphocytes T CD8+, Lymphocytes T cytotoxiques, Pneumopathie virale, Sous-populations de lymphocytes T.
- métabolisme : Antigènes CD, Cytotoxines.
- pathogénicité : Betacoronavirus.
- Adulte d'âge moyen, Femelle, Humains, Immunité cellulaire, Mâle, Pandémies, Sujet âgé de 80 ans ou plus.
English descriptors
- KwdEn :
- Aged, 80 and over (MeSH), Antigens, CD (metabolism), Betacoronavirus (pathogenicity), CD4-Positive T-Lymphocytes (immunology), CD4-Positive T-Lymphocytes (pathology), CD8-Positive T-Lymphocytes (immunology), CD8-Positive T-Lymphocytes (pathology), Coronavirus Infections (immunology), Cytotoxins (metabolism), Female (MeSH), Humans (MeSH), Immunity, Cellular (MeSH), Male (MeSH), Middle Aged (MeSH), Pandemics (MeSH), Pneumonia, Viral (immunology), T-Lymphocyte Subsets (immunology), T-Lymphocyte Subsets (pathology), T-Lymphocytes, Cytotoxic (immunology), T-Lymphocytes, Cytotoxic (pathology).
- MESH :
- chemical , metabolism : Antigens, CD, Cytotoxins.
- immunology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Coronavirus Infections, Pneumonia, Viral, T-Lymphocyte Subsets, T-Lymphocytes, Cytotoxic.
- pathogenicity : Betacoronavirus.
- pathology : CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, T-Lymphocyte Subsets, T-Lymphocytes, Cytotoxic.
- Aged, 80 and over, Female, Humans, Immunity, Cellular, Male, Middle Aged, Pandemics.
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.
DOI: 10.1128/mBio.02243-20
PubMed: 32948688
PubMed Central: PMC7502863
Affiliations:
Links toward previous steps (curation, corpus...)
Le document en format XML
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T Cell Response in Elderly COVID-19 Patients.</title>
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<country xml:lang="fr">Allemagne</country>
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<author><name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
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<author><name sortKey="Babel, Nina" sort="Babel, Nina" uniqKey="Babel N" first="Nina" last="Babel">Nina Babel</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne</wicri:regionArea>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
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<affiliation wicri:level="3"><nlm:affiliation>Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
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<affiliation wicri:level="3"><nlm:affiliation>Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
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<author><name sortKey="Westhoff, Timm" sort="Westhoff, Timm" uniqKey="Westhoff T" first="Timm" last="Westhoff">Timm Westhoff</name>
<affiliation wicri:level="1"><nlm:affiliation>Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum</wicri:regionArea>
<wicri:noRegion>Bochum</wicri:noRegion>
<wicri:noRegion>Bochum</wicri:noRegion>
<wicri:noRegion>Bochum</wicri:noRegion>
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<author><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
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<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
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<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
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<author><name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de.</nlm:affiliation>
<country wicri:rule="url">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
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<sourceDesc><biblStruct><analytic><title xml:lang="en">Impaired Cytotoxic CD8<sup>+</sup>
T Cell Response in Elderly COVID-19 Patients.</title>
<author><name sortKey="Westmeier, Jaana" sort="Westmeier, Jaana" uniqKey="Westmeier J" first="Jaana" last="Westmeier">Jaana Westmeier</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Paniskaki, Krystallenia" sort="Paniskaki, Krystallenia" uniqKey="Paniskaki K" first="Krystallenia" last="Paniskaki">Krystallenia Paniskaki</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne</wicri:regionArea>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Karakose, Zehra" sort="Karakose, Zehra" uniqKey="Karakose Z" first="Zehra" last="Karaköse">Zehra Karaköse</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Werner, Tanja" sort="Werner, Tanja" uniqKey="Werner T" first="Tanja" last="Werner">Tanja Werner</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sutter, Kathrin" sort="Sutter, Kathrin" uniqKey="Sutter K" first="Kathrin" last="Sutter">Kathrin Sutter</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Dolff, Sebastian" sort="Dolff, Sebastian" uniqKey="Dolff S" first="Sebastian" last="Dolff">Sebastian Dolff</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Overbeck, Marvin" sort="Overbeck, Marvin" uniqKey="Overbeck M" first="Marvin" last="Overbeck">Marvin Overbeck</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Limmer, Andreas" sort="Limmer, Andreas" uniqKey="Limmer A" first="Andreas" last="Limmer">Andreas Limmer</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Brenner, Thorsten" sort="Brenner, Thorsten" uniqKey="Brenner T" first="Thorsten" last="Brenner">Thorsten Brenner</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Berger, Marc M" sort="Berger, Marc M" uniqKey="Berger M" first="Marc M" last="Berger">Marc M. Berger</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Witzke, Oliver" sort="Witzke, Oliver" uniqKey="Witzke O" first="Oliver" last="Witzke">Oliver Witzke</name>
<affiliation wicri:level="1"><nlm:affiliation>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Trilling, Mirko" sort="Trilling, Mirko" uniqKey="Trilling M" first="Mirko" last="Trilling">Mirko Trilling</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Babel, Nina" sort="Babel, Nina" uniqKey="Babel N" first="Nina" last="Babel">Nina Babel</name>
<affiliation wicri:level="1"><nlm:affiliation>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne</wicri:regionArea>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
<wicri:noRegion>Herne</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Westhoff, Timm" sort="Westhoff, Timm" uniqKey="Westhoff T" first="Timm" last="Westhoff">Timm Westhoff</name>
<affiliation wicri:level="1"><nlm:affiliation>Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum</wicri:regionArea>
<wicri:noRegion>Bochum</wicri:noRegion>
<wicri:noRegion>Bochum</wicri:noRegion>
<wicri:noRegion>Bochum</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de.</nlm:affiliation>
<country wicri:rule="url">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
<author><name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name>
<affiliation wicri:level="1"><nlm:affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de.</nlm:affiliation>
<country wicri:rule="url">Allemagne</country>
<wicri:regionArea>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen</wicri:regionArea>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
<wicri:noRegion>Essen</wicri:noRegion>
</affiliation>
<affiliation wicri:level="3"><nlm:affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</nlm:affiliation>
<country xml:lang="fr">République populaire de Chine</country>
<wicri:regionArea>Joint International Laboratory of Infection and Immunity, HUST, Wuhan</wicri:regionArea>
<placeName><settlement type="city">Wuhan</settlement>
<region type="région">Hubei</region>
</placeName>
</affiliation>
</author>
</analytic>
<series><title level="j">mBio</title>
<idno type="eISSN">2150-7511</idno>
<imprint><date when="2020" type="published">2020</date>
</imprint>
</series>
</biblStruct>
</sourceDesc>
</fileDesc>
<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Aged, 80 and over (MeSH)</term>
<term>Antigens, CD (metabolism)</term>
<term>Betacoronavirus (pathogenicity)</term>
<term>CD4-Positive T-Lymphocytes (immunology)</term>
<term>CD4-Positive T-Lymphocytes (pathology)</term>
<term>CD8-Positive T-Lymphocytes (immunology)</term>
<term>CD8-Positive T-Lymphocytes (pathology)</term>
<term>Coronavirus Infections (immunology)</term>
<term>Cytotoxins (metabolism)</term>
<term>Female (MeSH)</term>
<term>Humans (MeSH)</term>
<term>Immunity, Cellular (MeSH)</term>
<term>Male (MeSH)</term>
<term>Middle Aged (MeSH)</term>
<term>Pandemics (MeSH)</term>
<term>Pneumonia, Viral (immunology)</term>
<term>T-Lymphocyte Subsets (immunology)</term>
<term>T-Lymphocyte Subsets (pathology)</term>
<term>T-Lymphocytes, Cytotoxic (immunology)</term>
<term>T-Lymphocytes, Cytotoxic (pathology)</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte d'âge moyen (MeSH)</term>
<term>Antigènes CD (métabolisme)</term>
<term>Betacoronavirus (pathogénicité)</term>
<term>Cytotoxines (métabolisme)</term>
<term>Femelle (MeSH)</term>
<term>Humains (MeSH)</term>
<term>Immunité cellulaire (MeSH)</term>
<term>Infections à coronavirus (immunologie)</term>
<term>Lymphocytes T CD4+ (anatomopathologie)</term>
<term>Lymphocytes T CD4+ (immunologie)</term>
<term>Lymphocytes T CD8+ (anatomopathologie)</term>
<term>Lymphocytes T CD8+ (immunologie)</term>
<term>Lymphocytes T cytotoxiques (anatomopathologie)</term>
<term>Lymphocytes T cytotoxiques (immunologie)</term>
<term>Mâle (MeSH)</term>
<term>Pandémies (MeSH)</term>
<term>Pneumopathie virale (immunologie)</term>
<term>Sous-populations de lymphocytes T (anatomopathologie)</term>
<term>Sous-populations de lymphocytes T (immunologie)</term>
<term>Sujet âgé de 80 ans ou plus (MeSH)</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Antigens, CD</term>
<term>Cytotoxins</term>
</keywords>
<keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Sous-populations de lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Infections à coronavirus</term>
<term>Lymphocytes T CD4+</term>
<term>Lymphocytes T CD8+</term>
<term>Lymphocytes T cytotoxiques</term>
<term>Pneumopathie virale</term>
<term>Sous-populations de lymphocytes T</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>Coronavirus Infections</term>
<term>Pneumonia, Viral</term>
<term>T-Lymphocyte Subsets</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Antigènes CD</term>
<term>Cytotoxines</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogenicity" xml:lang="en"><term>Betacoronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathogénicité" xml:lang="fr"><term>Betacoronavirus</term>
</keywords>
<keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>CD4-Positive T-Lymphocytes</term>
<term>CD8-Positive T-Lymphocytes</term>
<term>T-Lymphocyte Subsets</term>
<term>T-Lymphocytes, Cytotoxic</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Aged, 80 and over</term>
<term>Female</term>
<term>Humans</term>
<term>Immunity, Cellular</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Pandemics</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte d'âge moyen</term>
<term>Femelle</term>
<term>Humains</term>
<term>Immunité cellulaire</term>
<term>Mâle</term>
<term>Pandémies</term>
<term>Sujet âgé de 80 ans ou plus</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">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<sup>+</sup>
T cells, but not CD4<sup>+</sup>
T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8<sup>+</sup>
T cell subsets. PD-1-expressing CD8<sup>+</sup>
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<sup>+</sup>
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.<b>IMPORTANCE</b>
Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8<sup>+</sup>
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<sup>+</sup>
T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8<sup>+</sup>
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.</div>
</front>
</TEI>
<pubmed><MedlineCitation Status="MEDLINE" Owner="NLM"><PMID Version="1">32948688</PMID>
<DateCompleted><Year>2020</Year>
<Month>10</Month>
<Day>05</Day>
</DateCompleted>
<DateRevised><Year>2020</Year>
<Month>10</Month>
<Day>05</Day>
</DateRevised>
<Article PubModel="Electronic"><Journal><ISSN IssnType="Electronic">2150-7511</ISSN>
<JournalIssue CitedMedium="Internet"><Volume>11</Volume>
<Issue>5</Issue>
<PubDate><Year>2020</Year>
<Month>09</Month>
<Day>18</Day>
</PubDate>
</JournalIssue>
<Title>mBio</Title>
<ISOAbbreviation>mBio</ISOAbbreviation>
</Journal>
<ArticleTitle>Impaired Cytotoxic CD8<sup>+</sup>
T Cell Response in Elderly COVID-19 Patients.</ArticleTitle>
<ELocationID EIdType="pii" ValidYN="Y">e02243-20</ELocationID>
<ELocationID EIdType="doi" ValidYN="Y">10.1128/mBio.02243-20</ELocationID>
<Abstract><AbstractText>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<sup>+</sup>
T cells, but not CD4<sup>+</sup>
T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8<sup>+</sup>
T cell subsets. PD-1-expressing CD8<sup>+</sup>
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<sup>+</sup>
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.<b>IMPORTANCE</b>
Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8<sup>+</sup>
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<sup>+</sup>
T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8<sup>+</sup>
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.</AbstractText>
<CopyrightInformation>Copyright © 2020 Westmeier et al.</CopyrightInformation>
</Abstract>
<AuthorList CompleteYN="Y"><Author ValidYN="Y"><LastName>Westmeier</LastName>
<ForeName>Jaana</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Paniskaki</LastName>
<ForeName>Krystallenia</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Karaköse</LastName>
<ForeName>Zehra</ForeName>
<Initials>Z</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Werner</LastName>
<ForeName>Tanja</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Sutter</LastName>
<ForeName>Kathrin</ForeName>
<Initials>K</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dolff</LastName>
<ForeName>Sebastian</ForeName>
<Initials>S</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Overbeck</LastName>
<ForeName>Marvin</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Limmer</LastName>
<ForeName>Andreas</ForeName>
<Initials>A</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Liu</LastName>
<ForeName>Jia</ForeName>
<Initials>J</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zheng</LastName>
<ForeName>Xin</ForeName>
<Initials>X</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Brenner</LastName>
<ForeName>Thorsten</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Berger</LastName>
<ForeName>Marc M</ForeName>
<Initials>MM</Initials>
<AffiliationInfo><Affiliation>Department of Anesthesiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Witzke</LastName>
<ForeName>Oliver</ForeName>
<Initials>O</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, West German Centre of Infectious Diseases, University Hospital Essen, University Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Trilling</LastName>
<ForeName>Mirko</ForeName>
<Initials>M</Initials>
<Identifier Source="ORCID">0000-0003-3659-3541</Identifier>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Lu</LastName>
<ForeName>Mengji</ForeName>
<Initials>M</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Yang</LastName>
<ForeName>Dongliang</ForeName>
<Initials>D</Initials>
<AffiliationInfo><Affiliation>Department of Infectious Diseases, Union Hospital of Tonji Medical College, Huazhong University of Science and Technology, Wuhan, China.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Babel</LastName>
<ForeName>Nina</ForeName>
<Initials>N</Initials>
<AffiliationInfo><Affiliation>Center for Translational Medicine, Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Herne, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin, Germany.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Berlin Institute of Health, Berlin-Brandenburg Center for Regenerative Therapies, Berlin, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Westhoff</LastName>
<ForeName>Timm</ForeName>
<Initials>T</Initials>
<AffiliationInfo><Affiliation>Medical Department I, Marien Hospital Herne, University Hospital of the Ruhr University of Bochum, Bochum, Germany.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Dittmer</LastName>
<ForeName>Ulf</ForeName>
<Initials>U</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
<Author ValidYN="Y"><LastName>Zelinskyy</LastName>
<ForeName>Gennadiy</ForeName>
<Initials>G</Initials>
<AffiliationInfo><Affiliation>Institute for Virology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany ulf.dittmer@uni-due.de gennadiy.zelinskyy@uni-due.de.</Affiliation>
</AffiliationInfo>
<AffiliationInfo><Affiliation>Joint International Laboratory of Infection and Immunity, HUST, Wuhan, China.</Affiliation>
</AffiliationInfo>
</Author>
</AuthorList>
<Language>eng</Language>
<PublicationTypeList><PublicationType UI="D003160">Comparative Study</PublicationType>
<PublicationType UI="D016428">Journal Article</PublicationType>
<PublicationType UI="D013485">Research Support, Non-U.S. Gov't</PublicationType>
</PublicationTypeList>
<ArticleDate DateType="Electronic"><Year>2020</Year>
<Month>09</Month>
<Day>18</Day>
</ArticleDate>
</Article>
<MedlineJournalInfo><Country>United States</Country>
<MedlineTA>mBio</MedlineTA>
<NlmUniqueID>101519231</NlmUniqueID>
</MedlineJournalInfo>
<ChemicalList><Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D015703">Antigens, CD</NameOfSubstance>
</Chemical>
<Chemical><RegistryNumber>0</RegistryNumber>
<NameOfSubstance UI="D003603">Cytotoxins</NameOfSubstance>
</Chemical>
</ChemicalList>
<SupplMeshList><SupplMeshName Type="Disease" UI="C000657245">COVID-19</SupplMeshName>
<SupplMeshName Type="Organism" UI="C000656484">severe acute respiratory syndrome coronavirus 2</SupplMeshName>
</SupplMeshList>
<CitationSubset>IM</CitationSubset>
<MeshHeadingList><MeshHeading><DescriptorName UI="D000369" MajorTopicYN="N">Aged, 80 and over</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015703" MajorTopicYN="N">Antigens, CD</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D000073640" MajorTopicYN="N">Betacoronavirus</DescriptorName>
<QualifierName UI="Q000472" MajorTopicYN="N">pathogenicity</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D015496" MajorTopicYN="N">CD4-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018414" MajorTopicYN="N">CD8-Positive T-Lymphocytes</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D018352" MajorTopicYN="N">Coronavirus Infections</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D003603" MajorTopicYN="N">Cytotoxins</DescriptorName>
<QualifierName UI="Q000378" MajorTopicYN="N">metabolism</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D005260" MajorTopicYN="N">Female</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D006801" MajorTopicYN="N">Humans</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D007111" MajorTopicYN="N">Immunity, Cellular</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008297" MajorTopicYN="N">Male</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D008875" MajorTopicYN="N">Middle Aged</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D058873" MajorTopicYN="N">Pandemics</DescriptorName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D011024" MajorTopicYN="N">Pneumonia, Viral</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="Y">immunology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D016176" MajorTopicYN="N">T-Lymphocyte Subsets</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="N">pathology</QualifierName>
</MeshHeading>
<MeshHeading><DescriptorName UI="D013602" MajorTopicYN="N">T-Lymphocytes, Cytotoxic</DescriptorName>
<QualifierName UI="Q000276" MajorTopicYN="N">immunology</QualifierName>
<QualifierName UI="Q000473" MajorTopicYN="Y">pathology</QualifierName>
</MeshHeading>
</MeshHeadingList>
<KeywordList Owner="NOTNLM"><Keyword MajorTopicYN="Y">CD4+
</Keyword>
<Keyword MajorTopicYN="Y">CD8+
</Keyword>
<Keyword MajorTopicYN="Y">COVID-19</Keyword>
<Keyword MajorTopicYN="Y">PD-1</Keyword>
<Keyword MajorTopicYN="Y">SARS-CoV-2</Keyword>
<Keyword MajorTopicYN="Y">aging</Keyword>
<Keyword MajorTopicYN="Y">cytotoxic T cells</Keyword>
<Keyword MajorTopicYN="Y">granzyme</Keyword>
<Keyword MajorTopicYN="Y">perforin</Keyword>
</KeywordList>
</MedlineCitation>
<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2020</Year>
<Month>9</Month>
<Day>19</Day>
<Hour>5</Hour>
<Minute>29</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="pubmed"><Year>2020</Year>
<Month>9</Month>
<Day>20</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
<PubMedPubDate PubStatus="medline"><Year>2020</Year>
<Month>10</Month>
<Day>6</Day>
<Hour>6</Hour>
<Minute>0</Minute>
</PubMedPubDate>
</History>
<PublicationStatus>epublish</PublicationStatus>
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<ArticleId IdType="doi">10.1128/mBio.02243-20</ArticleId>
<ArticleId IdType="pmc">PMC7502863</ArticleId>
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<affiliations><list><country><li>Allemagne</li>
<li>République populaire de Chine</li>
</country>
<region><li>Berlin</li>
<li>Hubei</li>
</region>
<settlement><li>Berlin</li>
<li>Wuhan</li>
</settlement>
</list>
<tree><country name="Allemagne"><noRegion><name sortKey="Westmeier, Jaana" sort="Westmeier, Jaana" uniqKey="Westmeier J" first="Jaana" last="Westmeier">Jaana Westmeier</name>
</noRegion>
<name sortKey="Babel, Nina" sort="Babel, Nina" uniqKey="Babel N" first="Nina" last="Babel">Nina Babel</name>
<name sortKey="Babel, Nina" sort="Babel, Nina" uniqKey="Babel N" first="Nina" last="Babel">Nina Babel</name>
<name sortKey="Babel, Nina" sort="Babel, Nina" uniqKey="Babel N" first="Nina" last="Babel">Nina Babel</name>
<name sortKey="Berger, Marc M" sort="Berger, Marc M" uniqKey="Berger M" first="Marc M" last="Berger">Marc M. Berger</name>
<name sortKey="Brenner, Thorsten" sort="Brenner, Thorsten" uniqKey="Brenner T" first="Thorsten" last="Brenner">Thorsten Brenner</name>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<name sortKey="Dolff, Sebastian" sort="Dolff, Sebastian" uniqKey="Dolff S" first="Sebastian" last="Dolff">Sebastian Dolff</name>
<name sortKey="Karakose, Zehra" sort="Karakose, Zehra" uniqKey="Karakose Z" first="Zehra" last="Karaköse">Zehra Karaköse</name>
<name sortKey="Limmer, Andreas" sort="Limmer, Andreas" uniqKey="Limmer A" first="Andreas" last="Limmer">Andreas Limmer</name>
<name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
<name sortKey="Overbeck, Marvin" sort="Overbeck, Marvin" uniqKey="Overbeck M" first="Marvin" last="Overbeck">Marvin Overbeck</name>
<name sortKey="Paniskaki, Krystallenia" sort="Paniskaki, Krystallenia" uniqKey="Paniskaki K" first="Krystallenia" last="Paniskaki">Krystallenia Paniskaki</name>
<name sortKey="Sutter, Kathrin" sort="Sutter, Kathrin" uniqKey="Sutter K" first="Kathrin" last="Sutter">Kathrin Sutter</name>
<name sortKey="Trilling, Mirko" sort="Trilling, Mirko" uniqKey="Trilling M" first="Mirko" last="Trilling">Mirko Trilling</name>
<name sortKey="Werner, Tanja" sort="Werner, Tanja" uniqKey="Werner T" first="Tanja" last="Werner">Tanja Werner</name>
<name sortKey="Westhoff, Timm" sort="Westhoff, Timm" uniqKey="Westhoff T" first="Timm" last="Westhoff">Timm Westhoff</name>
<name sortKey="Witzke, Oliver" sort="Witzke, Oliver" uniqKey="Witzke O" first="Oliver" last="Witzke">Oliver Witzke</name>
<name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name>
</country>
<country name="République populaire de Chine"><region name="Hubei"><name sortKey="Sutter, Kathrin" sort="Sutter, Kathrin" uniqKey="Sutter K" first="Kathrin" last="Sutter">Kathrin Sutter</name>
</region>
<name sortKey="Dittmer, Ulf" sort="Dittmer, Ulf" uniqKey="Dittmer U" first="Ulf" last="Dittmer">Ulf Dittmer</name>
<name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name>
<name sortKey="Liu, Jia" sort="Liu, Jia" uniqKey="Liu J" first="Jia" last="Liu">Jia Liu</name>
<name sortKey="Lu, Mengji" sort="Lu, Mengji" uniqKey="Lu M" first="Mengji" last="Lu">Mengji Lu</name>
<name sortKey="Trilling, Mirko" sort="Trilling, Mirko" uniqKey="Trilling M" first="Mirko" last="Trilling">Mirko Trilling</name>
<name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<name sortKey="Yang, Dongliang" sort="Yang, Dongliang" uniqKey="Yang D" first="Dongliang" last="Yang">Dongliang Yang</name>
<name sortKey="Zelinskyy, Gennadiy" sort="Zelinskyy, Gennadiy" uniqKey="Zelinskyy G" first="Gennadiy" last="Zelinskyy">Gennadiy Zelinskyy</name>
<name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
<name sortKey="Zheng, Xin" sort="Zheng, Xin" uniqKey="Zheng X" first="Xin" last="Zheng">Xin Zheng</name>
</country>
</tree>
</affiliations>
</record>
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