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

TY - JOUR

T1 - SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19

AU - Braun, Julian

AU - Loyal, Lucie

AU - Frentsch, Marco

AU - Wendisch, Daniel

AU - Georg, Philipp

AU - Kurth, Florian

AU - Hippenstiel, Stefan

AU - Dingeldey, Manuela

AU - Kruse, Beate

AU - Fauchere, Florent

AU - Baysal, Emre

AU - Mangold, Maike

AU - Henze, Larissa

AU - Lauster, Roland

AU - Mall, Marcus A

AU - Beyer, Kirsten

AU - Röhmel, Jobst

AU - Voigt, Sebastian

AU - Schmitz, Jürgen

AU - Miltenyi, Stefan

AU - Demuth, Ilja

AU - Müller, Marcel A

AU - Hocke, Andreas

AU - Witzenrath, Martin

AU - Suttorp, Norbert

AU - Kern, Florian

AU - Reimer, Ulf

AU - Wenschuh, Holger

AU - Drosten, Christian

AU - Corman, Victor M

AU - Giesecke-Thiel, Claudia

AU - Sander, Leif Erik

AU - Thiel, Andreas

PY - 2020/11

Y1 - 2020/11

N2 - 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.

AB - 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.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Betacoronavirus/immunology

KW - CD4-Positive T-Lymphocytes/immunology

KW - COVID-19

KW - Cell Line

KW - Coronavirus 229E, Human/immunology

KW - Coronavirus Infections/immunology

KW - Coronavirus NL63, Human/immunology

KW - Coronavirus OC43, Human/immunology

KW - Cross Reactions

KW - Epitopes, T-Lymphocyte/immunology

KW - Female

KW - Healthy Volunteers

KW - Humans

KW - Lymphocyte Activation

KW - Male

KW - Middle Aged

KW - Pandemics

KW - Pneumonia, Viral/immunology

KW - SARS-CoV-2

KW - Spike Glycoprotein, Coronavirus/immunology

U2 - 10.1038/s41586-020-2598-9

DO - 10.1038/s41586-020-2598-9

M3 - SCORING: Journal article

C2 - 32726801

VL - 587

SP - 270

EP - 274

JO - NATURE

JF - NATURE

SN - 0028-0836

IS - 7833

ER -