Low-Avidity CD4 T Cell Responses to SARS-CoV-2 in Unexposed Individuals and Humans with Severe COVID-19.
Petra Bacher, Elisa Rosati, Daniela Esser, Gabriela Rios Martini, Carina Saggau, Esther Schiminsky, Justina Dargvainiene, Ina Schr��der, Imke Wieters, Yascha Khodamoradi, Fabian Eberhardt, Maria J G T Vehreschild, Holger Neb, Michael Sonntagbauer, Claudio Conrad, Florian Tran, Philip Rosenstiel, Robert Markewitz, Klaus-Peter Wandinger, Max Augustin, Jan Rybniker, Matthias Kochanek, Frank Leypoldt, Oliver A Cornely, Philipp Koehler, Andre Franke, Alexander Scheffold
Author Information
Petra Bacher: Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany. Electronic address: p.bacher@ikmb.uni-kiel.de.
Elisa Rosati: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Daniela Esser: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany.
Gabriela Rios Martini: Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany; Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Carina Saggau: Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany.
Esther Schiminsky: Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany.
Justina Dargvainiene: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany.
Ina Schr��der: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany.
Imke Wieters: Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt & Goethe University Frankfurt, Frankfurt am Main, Germany.
Yascha Khodamoradi: Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt & Goethe University Frankfurt, Frankfurt am Main, Germany.
Fabian Eberhardt: Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt & Goethe University Frankfurt, Frankfurt am Main, Germany.
Maria J G T Vehreschild: Department of Internal Medicine, Infectious Diseases, University Hospital Frankfurt & Goethe University Frankfurt, Frankfurt am Main, Germany.
Holger Neb: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
Michael Sonntagbauer: Department of Anesthesiology, Intensive Care Medicine and Pain Therapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
Claudio Conrad: Department of Internal Medicine, Hospital of Preetz, Preetz, Germany.
Florian Tran: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Internal Medicine I, UKSH Kiel, Germany.
Philip Rosenstiel: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Robert Markewitz: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany.
Klaus-Peter Wandinger: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany.
Max Augustin: University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; University of Cologne, Medical Faculty and University Hospital Cologne, German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
Jan Rybniker: University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; University of Cologne, Medical Faculty and University Hospital Cologne, German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.
Matthias Kochanek: University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany.
Frank Leypoldt: Institute of Clinical Chemistry, University Hospital Schleswig-Holstein, Kiel/ L��beck, Germany; Department of Neurology, University Hospital Schleswig-Holstein, Kiel, Germany.
Oliver A Cornely: University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; University of Cologne, Medical Faculty and University Hospital Cologne, German Center for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany; Clinical Trials Centre Cologne, ZKS K��ln, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Philipp Koehler: University of Cologne, Medical Faculty and University Hospital Cologne, Department I of Internal Medicine, Cologne, Germany; Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany; University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD), Cologne, Germany.
Andre Franke: Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany.
Alexander Scheffold: Institute of Immunology, Christian-Albrechts-University of Kiel & UKSH Schleswig-Holstein, Kiel, Germany.
CD4 T cells reactive against SARS-CoV-2 can be found in unexposed individuals, and these are suggested to arise in response to common cold coronavirus (CCCoV) infection. Here, we utilized SARS-CoV-2-reactive CD4 T cell enrichment to examine the antigen avidity and clonality of these cells, as well as the relative contribution of CCCoV cross-reactivity. SARS-CoV-2-reactive CD4 memory T cells were present in virtually all unexposed individuals examined, displaying low functional avidity and multiple, highly variable cross-reactivities that were not restricted to CCCoVs. SARS-CoV-2-reactive CD4 T cells from COVID-19 patients lacked cross-reactivity to CCCoVs, irrespective of strong memory T cell responses against CCCoV in all donors analyzed. In severe but not mild COVID-19, SARS-CoV-2-specific T cells displayed low functional avidity and clonality, despite increased frequencies. Our findings identify low-avidity CD4 T cell responses as a hallmark of severe COVID-19 and argue against a protective role for CCCoV-reactive T cells in SARS-CoV-2 infection.
