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SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19.
Nature. 2020 11; 587(7833):270-274.Nat

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.

Authors+Show Affiliations

Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Department of Hematology, Oncology and Tumor Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Berlin Institute of Health (BIH), Berlin, Germany.Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.Berlin Institute of Health (BIH), Berlin, Germany. Department of Infectious Diseases and Respiratory Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Berlin Institute of Health (BIH), Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.Medical Biotechnology, Institute for Biotechnology, Technische Universität Berlin, Berlin, Germany. Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany.Medical Biotechnology, Institute for Biotechnology, Technische Universität Berlin, Berlin, Germany.Medical Biotechnology, Institute for Biotechnology, Technische Universität Berlin, Berlin, Germany.Department of Infectious Diseases, Robert Koch Institut, Berlin, Germany.Miltenyi Biotec, Bergisch Gladbach, Germany.Miltenyi Biotec, Bergisch Gladbach, Germany.Interdisciplinary Metabolism Center, Biology of Aging (BoA) group, Charité-Universitätsmedizin Berlin, Berlin, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Berlin Institute of Health (BIH), Berlin, Germany.Berlin Institute of Health (BIH), Berlin, Germany.Berlin Institute of Health (BIH), Berlin, Germany.Department of Clinical and Experimental Medicine, Brighton and Sussex Medical School, Brighton, UK. JPT Peptide Technologies, Berlin, Germany.JPT Peptide Technologies, Berlin, Germany.JPT Peptide Technologies, Berlin, Germany.Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, Berlin, Germany. Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Institute of Virology, Charité-Universitätsmedizin Berlin, Berlin, Germany.Max Planck Institute for Molecular Genetics, Berlin, Germany. giesecke@molgen.mpg.de.Berlin Institute of Health (BIH), Berlin, Germany. leif-erik.sander@charite.de.Si-M/'Der Simulierte Mensch', Technische Universität Berlin and Charité-Universitätsmedizin Berlin, Berlin, Germany. andreas.thiel@charite.de. Regenerative Immunology and Aging, BIH Center for Regenerative Therapies, Charité-Universitätsmedizin Berlin, Berlin, Germany. andreas.thiel@charite.de.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32726801

Citation

Braun, Julian, et al. "SARS-CoV-2-reactive T Cells in Healthy Donors and Patients With COVID-19." Nature, vol. 587, no. 7833, 2020, pp. 270-274.
Braun J, Loyal L, Frentsch M, et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature. 2020;587(7833):270-274.
Braun, J., Loyal, L., Frentsch, M., Wendisch, D., Georg, P., Kurth, F., Hippenstiel, S., Dingeldey, M., Kruse, B., Fauchere, F., Baysal, E., Mangold, M., Henze, L., Lauster, R., Mall, M. A., Beyer, K., Röhmel, J., Voigt, S., Schmitz, J., ... Thiel, A. (2020). SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature, 587(7833), 270-274. https://doi.org/10.1038/s41586-020-2598-9
Braun J, et al. SARS-CoV-2-reactive T Cells in Healthy Donors and Patients With COVID-19. Nature. 2020;587(7833):270-274. PubMed PMID: 32726801.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2020/07/29/ PY - 2020/04/09/received PY - 2020/07/22/accepted PY - 2020/7/30/pubmed PY - 2020/11/20/medline PY - 2020/7/30/entrez SP - 270 EP - 274 JF - Nature JO - Nature VL - 587 IS - 7833 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. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32726801/SARS_CoV_2_reactive_T_cells_in_healthy_donors_and_patients_with_COVID_19_ L2 - https://doi.org/10.1038/s41586-020-2598-9 DB - PRIME DP - Unbound Medicine ER -