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

Author

Listed:
  • Julian Braun

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Lucie Loyal

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Marco Frentsch

    (Charité–Universitätsmedizin Berlin)

  • Daniel Wendisch

    (Berlin Institute of Health (BIH))

  • Philipp Georg

    (Charité-Universitätsmedizin Berlin)

  • Florian Kurth

    (Berlin Institute of Health (BIH)
    Charité-Universitätsmedizin Berlin
    University Medical Center Hamburg–Eppendorf)

  • Stefan Hippenstiel

    (Berlin Institute of Health (BIH))

  • Manuela Dingeldey

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Beate Kruse

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Florent Fauchere

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Emre Baysal

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Maike Mangold

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Larissa Henze

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Roland Lauster

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    University Medical Center Hamburg-Eppendorf)

  • Marcus A. Mall

    (Technische Universität Berlin
    Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin)

  • Kirsten Beyer

    (Technische Universität Berlin)

  • Jobst Röhmel

    (Technische Universität Berlin)

  • Sebastian Voigt

    (Robert Koch Institut)

  • Jürgen Schmitz

    (Miltenyi Biotec)

  • Stefan Miltenyi

    (Miltenyi Biotec)

  • Ilja Demuth

    (Charité–Universitätsmedizin Berlin)

  • Marcel A. Müller

    (Charité–Universitätsmedizin Berlin)

  • Andreas Hocke

    (Berlin Institute of Health (BIH))

  • Martin Witzenrath

    (Berlin Institute of Health (BIH))

  • Norbert Suttorp

    (Berlin Institute of Health (BIH))

  • Florian Kern

    (Brighton and Sussex Medical School
    JPT Peptide Technologies)

  • Ulf Reimer

    (JPT Peptide Technologies)

  • Holger Wenschuh

    (JPT Peptide Technologies)

  • Christian Drosten

    (Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

  • Victor M. Corman

    (Charité–Universitätsmedizin Berlin)

  • Claudia Giesecke-Thiel

    (Max Planck Institute for Molecular Genetics)

  • Leif Erik Sander

    (Berlin Institute of Health (BIH))

  • Andreas Thiel

    (Technische Universität Berlin and Charité–Universitätsmedizin Berlin
    Charité–Universitätsmedizin Berlin)

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.

Suggested Citation

  • Julian Braun & Lucie Loyal & Marco Frentsch & Daniel Wendisch & Philipp Georg & Florian Kurth & Stefan Hippenstiel & Manuela Dingeldey & Beate Kruse & Florent Fauchere & Emre Baysal & Maike Mangold & , 2020. "SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19," Nature, Nature, vol. 587(7833), pages 270-274, November.
  • Handle: RePEc:nat:nature:v:587:y:2020:i:7833:d:10.1038_s41586-020-2598-9
    DOI: 10.1038/s41586-020-2598-9
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    Cited by:

    1. Daan K. J. Pieren & Sebastián G. Kuguel & Joel Rosado & Alba G. Robles & Joan Rey-Cano & Cristina Mancebo & Juliana Esperalba & Vicenç Falcó & María J. Buzón & Meritxell Genescà, 2023. "Limited induction of polyfunctional lung-resident memory T cells against SARS-CoV-2 by mRNA vaccination compared to infection," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    2. Eva-Maria Jacobsen & Dorit Fabricius & Magdalena Class & Fernando Topfstedt & Raquel Lorenzetti & Iga Janowska & Franziska Schmidt & Julian Staniek & Maria Zernickel & Thomas Stamminger & Andrea N. Di, 2022. "High antibody levels and reduced cellular response in children up to one year after SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    3. Rúbens Prince dos Santos Alves & Julia Timis & Robyn Miller & Kristen Valentine & Paolla Beatriz Almeida Pinto & Andrew Gonzalez & Jose Angel Regla-Nava & Erin Maule & Michael N. Nguyen & Norazizah Sh, 2024. "Human coronavirus OC43-elicited CD4+ T cells protect against SARS-CoV-2 in HLA transgenic mice," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    4. Magen E. Francis & Ethan B. Jansen & Anthony Yourkowski & Alaa Selim & Cynthia L. Swan & Brian K. MacPhee & Brittany Thivierge & Rachelle Buchanan & Kerry J. Lavender & Joseph Darbellay & Matthew B. R, 2023. "Previous infection with seasonal coronaviruses does not protect male Syrian hamsters from challenge with SARS-CoV-2," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    5. Dhiraj Mannar & James W. Saville & Chad Poloni & Xing Zhu & Alison Bezeruk & Keith Tidey & Sana Ahmed & Katharine S. Tuttle & Faezeh Vahdatihassani & Spencer Cholak & Laura Cook & Theodore S. Steiner , 2024. "Altered receptor binding, antibody evasion and retention of T cell recognition by the SARS-CoV-2 XBB.1.5 spike protein," Nature Communications, Nature, vol. 15(1), pages 1-11, December.
    6. Iris N. Pardieck & Tetje C. van der Sluis & Esmé T. I. van der Gracht & Dominique M. B. Veerkamp & Felix M. Behr & Suzanne van Duikeren & Guillaume Beyrend & Jasper Rip & Reza Nadafi & Elham Beyranvan, 2022. "A third vaccination with a single T cell epitope confers protection in a murine model of SARS-CoV-2 infection," Nature Communications, Nature, vol. 13(1), pages 1-11, December.
    7. Tabea M. Eser & Olga Baranov & Manuel Huth & Mohammed I. M. Ahmed & Flora Deák & Kathrin Held & Luming Lin & Kami Pekayvaz & Alexander Leunig & Leo Nicolai & Georgios Pollakis & Marcus Buggert & David, 2023. "Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion," Nature Communications, Nature, vol. 14(1), pages 1-13, December.
    8. Meng Wang & Adeline Dehlinger & Camila Fernández Zapata & Maya Golan & Gerardina Gallaccio & Leif E. Sander & Stephan Schlickeiser & Desiree Kunkel & Tanja Schmitz-Hübsch & Birgit Sawitzki & Arnon Kar, 2023. "Associations of myeloid cells with cellular and humoral responses following vaccinations in patients with neuroimmunological diseases," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    9. Atienza-Diez, Iker & Seoane, Luís F., 2023. "Long- and short-term effects of cross-immunity in epidemic dynamics," Chaos, Solitons & Fractals, Elsevier, vol. 174(C).
    10. Jonas S. Heitmann & Claudia Tandler & Maddalena Marconato & Annika Nelde & Timorshah Habibzada & Susanne M. Rittig & Christian M. Tegeler & Yacine Maringer & Simon U. Jaeger & Monika Denk & Marion Ric, 2023. "Phase I/II trial of a peptide-based COVID-19 T-cell activator in patients with B-cell deficiency," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    11. Aloysious Ssemaganda & Huong Mai Nguyen & Faisal Nuhu & Naima Jahan & Catherine M. Card & Sandra Kiazyk & Giulia Severini & Yoav Keynan & Ruey-Chyi Su & Hezhao Ji & Bernard Abrenica & Paul J. McLaren , 2022. "Expansion of cytotoxic tissue-resident CD8+ T cells and CCR6+CD161+ CD4+ T cells in the nasal mucosa following mRNA COVID-19 vaccination," Nature Communications, Nature, vol. 13(1), pages 1-9, December.
    12. Tianqi Song & Yishi Wang & Xi Gu & Sijia Qiao, 2023. "Modeling the Within-Host Dynamics of SARS-CoV-2 Infection Based on Antiviral Treatment," Mathematics, MDPI, vol. 11(16), pages 1-19, August.
    13. Salim S Abdool Karim & Segenet Kelemu & Cheryl Baxter, 2021. "COVID-19 in Africa: Catalyzing change for sustainable development," PLOS Medicine, Public Library of Science, vol. 18(11), pages 1-4, November.
    14. Julia T. Castro & Patrick Azevedo & Marcílio J. Fumagalli & Natalia S. Hojo-Souza & Natalia Salazar & Gregório G. Almeida & Livia I. Oliveira & Lídia Faustino & Lis R. Antonelli & Tomas G. Marçal & Ma, 2022. "Promotion of neutralizing antibody-independent immunity to wild-type and SARS-CoV-2 variants of concern using an RBD-Nucleocapsid fusion protein," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    15. Mikhael D. Manurung & Friederike Sonnet & Marie-Astrid Hoogerwerf & Jacqueline J. Janse & Yvonne Kruize & Laura de Bes-Roeleveld & Marion König & Alex Loukas & Benjamin G. Dewals & Taniawati Supali & , 2024. "Controlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    16. Deanna M. Santer & Daniel Li & Yanal Ghosheh & Muhammad Atif Zahoor & Dhanvi Prajapati & Bettina E. Hansen & D. Lorne J. Tyrrell & Jordan J. Feld & Adam J. Gehring, 2022. "Interferon-λ treatment accelerates SARS-CoV-2 clearance despite age-related delays in the induction of T cell immunity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    17. Thomas Wieland, 2020. "Flatten the Curve! Modeling SARS-CoV-2/COVID-19 Growth in Germany at the County Level," REGION, European Regional Science Association, vol. 7, pages 43-83.

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