Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients

Summary: T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all...

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Main Authors: Constantin J. Thieme, Moritz Anft, Krystallenia Paniskaki, Arturo Blazquez-Navarro, Adrian Doevelaar, Felix S. Seibert, Bodo Hoelzer, Margarethe Justine Konik, Marc Moritz Berger, Thorsten Brenner, Clemens Tempfer, Carsten Watzl, Toni L. Meister, Stephanie Pfaender, Eike Steinmann, Sebastian Dolff, Ulf Dittmer, Timm H. Westhoff, Oliver Witzke, Ulrik Stervbo, Toralf Roch, Nina Babel
Format: Article
Language:English
Published: Elsevier 2020-09-01
Series:Cell Reports Medicine
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S266637912030118X
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author Constantin J. Thieme
Moritz Anft
Krystallenia Paniskaki
Arturo Blazquez-Navarro
Adrian Doevelaar
Felix S. Seibert
Bodo Hoelzer
Margarethe Justine Konik
Marc Moritz Berger
Thorsten Brenner
Clemens Tempfer
Carsten Watzl
Toni L. Meister
Stephanie Pfaender
Eike Steinmann
Sebastian Dolff
Ulf Dittmer
Timm H. Westhoff
Oliver Witzke
Ulrik Stervbo
Toralf Roch
Nina Babel
spellingShingle Constantin J. Thieme
Moritz Anft
Krystallenia Paniskaki
Arturo Blazquez-Navarro
Adrian Doevelaar
Felix S. Seibert
Bodo Hoelzer
Margarethe Justine Konik
Marc Moritz Berger
Thorsten Brenner
Clemens Tempfer
Carsten Watzl
Toni L. Meister
Stephanie Pfaender
Eike Steinmann
Sebastian Dolff
Ulf Dittmer
Timm H. Westhoff
Oliver Witzke
Ulrik Stervbo
Toralf Roch
Nina Babel
Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
Cell Reports Medicine
COVID-19
SARS-CoV-2
immunity
spike
nucleocapsid
S/M/N protein-reactive T cells
author_facet Constantin J. Thieme
Moritz Anft
Krystallenia Paniskaki
Arturo Blazquez-Navarro
Adrian Doevelaar
Felix S. Seibert
Bodo Hoelzer
Margarethe Justine Konik
Marc Moritz Berger
Thorsten Brenner
Clemens Tempfer
Carsten Watzl
Toni L. Meister
Stephanie Pfaender
Eike Steinmann
Sebastian Dolff
Ulf Dittmer
Timm H. Westhoff
Oliver Witzke
Ulrik Stervbo
Toralf Roch
Nina Babel
author_sort Constantin J. Thieme
title Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
title_short Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
title_full Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
title_fullStr Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
title_full_unstemmed Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 Patients
title_sort robust t cell response toward spike, membrane, and nucleocapsid sars-cov-2 proteins is not associated with recovery in critical covid-19 patients
publisher Elsevier
series Cell Reports Medicine
issn 2666-3791
publishDate 2020-09-01
description Summary: T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.
topic COVID-19
SARS-CoV-2
immunity
spike
nucleocapsid
S/M/N protein-reactive T cells
url http://www.sciencedirect.com/science/article/pii/S266637912030118X
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spelling doaj-e9bfff21d5a24fd6baf7d0d9d2173a5a2020-11-25T04:00:53ZengElsevierCell Reports Medicine2666-37912020-09-0116100092Robust T Cell Response Toward Spike, Membrane, and Nucleocapsid SARS-CoV-2 Proteins Is Not Associated with Recovery in Critical COVID-19 PatientsConstantin J. Thieme0Moritz Anft1Krystallenia Paniskaki2Arturo Blazquez-Navarro3Adrian Doevelaar4Felix S. Seibert5Bodo Hoelzer6Margarethe Justine Konik7Marc Moritz Berger8Thorsten Brenner9Clemens Tempfer10Carsten Watzl11Toni L. Meister12Stephanie Pfaender13Eike Steinmann14Sebastian Dolff15Ulf Dittmer16Timm H. Westhoff17Oliver Witzke18Ulrik Stervbo19Toralf Roch20Nina Babel21Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Department of Anesthesiology and Intensive Care Medicine, Essen, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Department of Anesthesiology and Intensive Care Medicine, Essen, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Department of Gynecology and Obstetrics, Herne, North Rhine-Westphalia, GermanyLeibniz Research Centre for Working Environment and Human Factors at the Technical University Dortmund (IfADo), Department of Immunology Dortmund, North Rhine-Westphalia, GermanyRuhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, GermanyRuhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, GermanyRuhr-University Bochum, Department of Molecular and Medical Virology, Bochum, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Institute for Virology, Essen, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyUniversity Duisburg-Essen, University Hospital Essen, Department of Infectious Diseases, West-German Centre for Infectious Diseases, Essen, North Rhine-Westphalia, GermanyRuhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, BIH Center for Regenerative Therapies, Berlin, Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute of Medical Immunology, Berlin, Berlin, Germany; Ruhr-University Bochum, Marien Hospital Herne, University Hospital of the Ruhr-University Bochum, Center for Translational Medicine and Immune Diagnostics Laboratory, Medical Department I, Herne, North Rhine-Westphalia, Germany; Corresponding authorSummary: T cell immunity toward SARS-CoV-2 spike (S-), membrane (M-), and nucleocapsid (N-) proteins may define COVID-19 severity. Therefore, we compare the SARS-CoV-2-reactive T cell responses in moderate, severe, and critical COVID-19 patients and unexposed donors. Overlapping peptide pools of all three proteins induce SARS-CoV-2-reactive T cell response with dominance of CD4+ over CD8+ T cells and demonstrate interindividual immunity against the three proteins. M-protein induces the highest frequencies of CD4+ T cells, suggesting its relevance for diagnosis and vaccination. The T cell response of critical COVID-19 patients is robust and comparable or even superior to non-critical patients. Virus clearance and COVID-19 survival are not associated with either SARS-CoV-2 T cell kinetics or magnitude of T cell responses, respectively. Thus, our data do not support the hypothesis of insufficient SARS-CoV-2-reactive immunity in critical COVID-19. Conversely, it indicates that activation of differentiated memory effector T cells could cause hyperreactivity and immunopathogenesis in critical patients.http://www.sciencedirect.com/science/article/pii/S266637912030118XCOVID-19SARS-CoV-2immunityspikenucleocapsidS/M/N protein-reactive T cells