SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

Julian Braun, Lucie Loyal, Marco Frentsch, Daniel Wendisch, Philipp Georg, Florian Kurth, Stefan Hippenstiel, Manuela Dingeldey, Beate Kruse, Florent Fauchere, Emre Baysal, Maike Mangold, Larissa Henze, Roland Lauster, Marcus A. Mall, Kirsten Beyer, Jobst Röhmel, Sebastian Voigt, Jürgen Schmitz, Stefan Miltenyi, Ilja Demuth, Marcel A. Müller, Andreas Hocke, Martin Witzenrath, Norbert Suttorp, Florian Kern, Ulf Reimer, Holger Wenschuh, Christian Drosten, Victor M. Corman, Claudia Giesecke-Thiel (), Leif Erik Sander () and Andreas Thiel ()
Additional contact information
Julian Braun: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Lucie Loyal: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Marco Frentsch: Charité–Universitätsmedizin Berlin
Daniel Wendisch: Berlin Institute of Health (BIH)
Philipp Georg: Charité-Universitätsmedizin Berlin
Florian Kurth: Berlin Institute of Health (BIH)
Stefan Hippenstiel: Berlin Institute of Health (BIH)
Manuela Dingeldey: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Beate Kruse: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Florent Fauchere: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Emre Baysal: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Maike Mangold: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Larissa Henze: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Roland Lauster: Technische Universität Berlin and Charité–Universitätsmedizin Berlin
Marcus A. Mall: Technische Universität Berlin
Kirsten Beyer: Technische Universität Berlin
Jobst Röhmel: Technische Universität Berlin
Sebastian Voigt: Robert Koch Institut
Jürgen Schmitz: Miltenyi Biotec
Stefan Miltenyi: Miltenyi Biotec
Ilja Demuth: Charité–Universitätsmedizin Berlin
Marcel A. Müller: Charité–Universitätsmedizin Berlin
Andreas Hocke: Berlin Institute of Health (BIH)
Martin Witzenrath: Berlin Institute of Health (BIH)
Norbert Suttorp: Berlin Institute of Health (BIH)
Florian Kern: Brighton and Sussex Medical School
Ulf Reimer: JPT Peptide Technologies
Holger Wenschuh: JPT Peptide Technologies
Christian Drosten: Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin
Victor M. Corman: Charité–Universitätsmedizin Berlin
Claudia Giesecke-Thiel: Max Planck Institute for Molecular Genetics
Leif Erik Sander: Berlin Institute of Health (BIH)
Andreas Thiel: Technische Universität Berlin and Charité–Universitätsmedizin Berlin

Nature, 2020, vol. 587, issue 7833, 270-274

Abstract: Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic1,2. Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes remain unresolved. Here we investigated CD4+ T cells that are reactive against the spike glycoprotein of SARS-CoV-2 in the peripheral blood of patients with COVID-19 and SARS-CoV-2-unexposed healthy donors. We detected spike-reactive CD4+ T cells not only in 83% of patients with COVID-19 but also in 35% of healthy donors. Spike-reactive CD4+ T cells in healthy donors were primarily active against C-terminal epitopes in the spike protein, which show a higher homology to spike glycoproteins of human endemic coronaviruses, compared with N-terminal epitopes. Spike-protein-reactive T cell lines generated from SARS-CoV-2-naive healthy donors responded similarly to the C-terminal region of the spike proteins of the human endemic coronaviruses 229E and OC43, as well as that of SARS-CoV-2. This results indicate that spike-protein cross-reactive T cells are present, which were probably generated during previous encounters with endemic coronaviruses. The effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined in larger cohorts. However, the presence of spike-protein cross-reactive T cells in a considerable fraction of the general population may affect the dynamics of the current pandemic, and has important implications for the design and analysis of upcoming trials investigating COVID-19 vaccines.

Date: 2020
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DOI: 10.1038/s41586-020-2598-9

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