Journal Article

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

Wenschuh, Holger, Corman, Victor M., Baysal, Emre, Dingeldey, Manuela, Müller, Marcel A., Giesecke-Thiel, Claudia, Beyer, Kirsten, Hocke, Andreas, Schmitz, Jürgen, Georg, Philipp, Voigt, Sebastian, Kern, Florian, Wendisch, Daniel, Loyal, Lucie, Miltenyi, Stefan, Sander, Leif Erik, Mall, Marcus A., Drosten, Christian, Witzenrath, Martin, Demuth, Ilja, Suttorp, Norbert, Frentsch, Marco, Lauster, Roland, Reimer, Ulf, Thiel, Andreas, Kurth, Florian, Fauchere, Florent, Röhmel, Jobst, Hippenstiel, Stefan, Mangold, Maike, Braun, Julian, Henze, Larissa, Kruse, Beate

2020

Overview

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused the rapidly unfolding coronavirus disease 2019 (COVID-19) pandemic 1 , 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. A study of patients with COVID-19 and healthy donors found CD4 + T cells that react to the spike protein of SARS-CoV-2 and human endemic coronaviruses; however, the effect of pre-existing SARS-CoV-2 cross-reactive T cells on clinical outcomes remains to be determined.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 13 / 13/1 / 13/31 / 14 / 631/250/2152/1566/1571 / 631/326/596/4130 / 692/699/255/2514 / 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 / Humanities and Social Sciences / Humans / Infections / Lymphocyte Activation / Lymphocytes / Lymphocytes T / Male / Middle Aged / multidisciplinary / Organ donors / Pandemics / Peptides / Peripheral blood / Pneumonia, Viral - immunology / Proteins / Respiratory diseases / Respiratory failure / SARS-CoV-2 / Science / Science (multidisciplinary) / Serology / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Spike Glycoprotein, Coronavirus - immunology / Spike protein / T cell receptors / T cells / Viral diseases