SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19
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SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. / 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.
In: NATURE, Vol. 587, No. 7833, 11.2020, p. 270-274.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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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 -