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SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself

Author

Listed:
  • Marta Ferreira-Gomes

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Andrey Kruglov

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    M.V. Lomonosov Moscow State University
    Russian Academy of Sciences)

  • Pawel Durek

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Frederik Heinrich

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Caroline Tizian

    (Charité-Universitätsmedizin Berlin
    Berlin Institute of Health (BIH)
    Deutsches Rheuma-Forschungszentrum)

  • Gitta Anne Heinz

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Anna Pascual-Reguant

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Weijie Du

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Ronja Mothes

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Chaofan Fan

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Stefan Frischbutter

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Katharina Habenicht

    (Friedrich-Alexander-University Erlangen-Nuremberg)

  • Lisa Budzinski

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Justus Ninnemann

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Peter K. Jani

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Gabriela Maria Guerra

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Katrin Lehmann

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Mareen Matz

    (Charité Universitätsmedizin Berlin)

  • Lennard Ostendorf

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Lukas Heiberger

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Hyun-Dong Chang

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Institute of Biotechnology)

  • Sandy Bauherr

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Marcus Maurer

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Günther Schönrich

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Martin Raftery

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Tilmann Kallinich

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Berlin Institute of Health (BIH)
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Marcus Alexander Mall

    (Berlin Institute of Health (BIH)
    Humboldt-Universität zu Berlin, and Berlin Institute of Health
    German Centre for Lung Research (DZL), associated partner site)

  • Stefan Angermair

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Sascha Treskatsch

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Thomas Dörner

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Victor Max Corman

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Andreas Diefenbach

    (Charité-Universitätsmedizin Berlin
    Berlin Institute of Health (BIH)
    Deutsches Rheuma-Forschungszentrum)

  • Hans-Dieter Volk

    (Charité Universitätsmedizin Berlin
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Sefer Elezkurtaj

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Thomas H. Winkler

    (Friedrich-Alexander-University Erlangen-Nuremberg)

  • Jun Dong

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Anja Erika Hauser

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Helena Radbruch

    (Humboldt-Universität zu Berlin, and Berlin Institute of Health)

  • Mario Witkowski

    (Charité-Universitätsmedizin Berlin
    Berlin Institute of Health (BIH)
    Deutsches Rheuma-Forschungszentrum)

  • Fritz Melchers

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Andreas Radbruch

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association)

  • Mir-Farzin Mashreghi

    (Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association
    Charité Universitätsmedizin Berlin)

Abstract

The pathogenesis of severe COVID-19 reflects an inefficient immune reaction to SARS-CoV-2. Here we analyze, at the single cell level, plasmablasts egressed into the blood to study the dynamics of adaptive immune response in COVID-19 patients requiring intensive care. Before seroconversion in response to SARS-CoV-2 spike protein, peripheral plasmablasts display a type 1 interferon-induced gene expression signature; however, following seroconversion, plasmablasts lose this signature, express instead gene signatures induced by IL-21 and TGF-β, and produce mostly IgG1 and IgA1. In the sustained immune reaction from COVID-19 patients, plasmablasts shift to the expression of IgA2, thereby reflecting an instruction by TGF-β. Despite their continued presence in the blood, plasmablasts are not found in the lungs of deceased COVID-19 patients, nor does patient IgA2 binds to the dominant antigens of SARS-CoV-2. Our results thus suggest that, in severe COVID-19, SARS-CoV-2 triggers a chronic immune reaction that is instructed by TGF-β, and is distracted from itself.

Suggested Citation

  • Marta Ferreira-Gomes & Andrey Kruglov & Pawel Durek & Frederik Heinrich & Caroline Tizian & Gitta Anne Heinz & Anna Pascual-Reguant & Weijie Du & Ronja Mothes & Chaofan Fan & Stefan Frischbutter & Kat, 2021. "SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-22210-3
    DOI: 10.1038/s41467-021-22210-3
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    Cited by:

    1. Junedh M. Amrute & Alexandra M. Perry & Gautam Anand & Carlos Cruchaga & Karl G. Hock & Christopher W. Farnsworth & Gwendalyn J. Randolph & Kory J. Lavine & Ashley L. Steed, 2022. "Cell specific peripheral immune responses predict survival in critical COVID-19 patients," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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