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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic . Clinical manifestations of COVID-19 vary, ranging from asymptomatic infection to respiratory failure. The mechanisms that determine such variable outcomes rema...

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Bibliographic Details
Published in:Nature (London) 2020-11, Vol.587 (7833), p.270-274
Main Authors: Braun, Julian, Loyal, Lucie, Frentsch, Marco, Wendisch, Daniel, Georg, Philipp, Kurth, Florian, Hippenstiel, Stefan, Dingeldey, Manuela, Kruse, Beate, Fauchere, Florent, Baysal, Emre, Mangold, Maike, Henze, Larissa, Lauster, Roland, Mall, Marcus A, Beyer, Kirsten, Röhmel, Jobst, Voigt, Sebastian, Schmitz, Jürgen, Miltenyi, Stefan, Demuth, Ilja, Müller, Marcel A, Hocke, Andreas, Witzenrath, Martin, Suttorp, Norbert, Kern, Florian, Reimer, Ulf, Wenschuh, Holger, Drosten, Christian, Corman, Victor M, Giesecke-Thiel, Claudia, Sander, Leif Erik, Thiel, Andreas
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Amino acids
Analysis
Antibodies
Antigens
Asymptomatic
Asymptomatic infection
Betacoronavirus - immunology
CD4 antigen
CD4-Positive T-Lymphocytes - immunology
Cell Line
Cell lines
Clinical trials
Control
Coronaviridae
Coronavirus 229E, Human - immunology
Coronavirus Infections - immunology
Coronavirus NL63, Human - immunology
Coronavirus OC43, Human - immunology
Coronaviruses
COVID-19
COVID-19 vaccines
Cross Reactions
Epitopes
Epitopes, T-Lymphocyte - immunology
Female
Genetic aspects
Glycoproteins
Health care
Healthy Volunteers
Homology
Humans
Infections
Lymphocyte Activation
Lymphocytes
Lymphocytes T
Male
Middle Aged
Organ donors
Pandemics
Peptides
Peripheral blood
Pneumonia, Viral - immunology
Proteins
Respiratory diseases
Respiratory failure
SARS-CoV-2
Serology
Severe acute respiratory syndrome
Severe acute respiratory syndrome coronavirus 2
Spike glycoprotein
Spike Glycoprotein, Coronavirus - immunology
Spike protein
T cell receptors
T cells
Vaccines
Viral diseases
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Summary:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic . 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.
ISSN:0028-0836
1476-4687
DOI:10.1038/s41586-020-2598-9