ArticleNature communications2021
SARS-CoV-2 in severe COVID-19 induces a TGF-β-dominated chronic immune response that does not target itself.
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In one paragraph
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 134 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
134citing papers in PubMed, 1 pooled it
14.1field-weighted citation impact, top 1% of its field
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
134 citing papers in PubMed, 1 synthesis or guideline pooled it, 224 citations in OpenAlex.
- Adaptive immunity to SARS-CoV-2 infection: A systematic review.Frontiers in immunology · 2022Pooled it
- Use ofFrontiers in immunology · 2023Trial
- Longitudinal transcriptional analysis of peripheral blood leukocytes in COVID-19 convalescent donors.Journal of translational medicine · 2022Trial
- Altered increase in STAT1 expression and phosphorylation in severe COVID-19.European journal of immunology · 2022Trial
- Polyplex of peptide-mannan and RNA for intranasal delivery of TGF-β siRNA in treatment of pulmonary fibrosis.Bioactive materials · 2026Article
- Biochemical insights and microRNA profiling via next-generation sequencing in moderate and severe COVID-19 cases.Clinics (Sao Paulo, Brazil) · 2026Article
- The Effects of Past COVID-19 and Vaccination on Antibody Levels, Cellular Immunity, and Cytokine Production by Peripheral Blood Mononuclear Cells.Biomedicines · 2026Article
- Host transcriptomic analysis reveals a defective intracellular environment that limits SARS-CoV-2 replication in CFTR-deficient airway epithelium.Frontiers in cellular and infection microbiology · 2026Article
- Nicheformer: a foundation model for single-cell and spatial omics.Nature methods · 2025Article
- Enteric nervous system-derived VIP restrains differentiation of LGR5Nature immunology · 2025Article
- COVID-19 Hijacking of the Host Epigenome: Mechanisms, Biomarkers and Long-Term Consequences.International journal of molecular sciences · 2025Review
- An RGD motif on SARS-CoV-2 Spike induces TGF-β signaling and downregulates interferon.Journal of virology · 2025Article
- Activin A activation of Smad3 mitigates innate inflammation in mouse models of psoriasis and sepsis.The Journal of clinical investigation · 2025Article
- Article
- A single-nucleus and spatial transcriptomic atlas of the COVID-19 liver reveals topological, functional, and regenerative organ disruption in patients.Genome biology · 2025Article
- Effector CD8 T cell differentiation in primary and breakthrough SARS-CoV-2 infection in mice.Communications biology · 2025Article
- Article
- Genetic Variants in Genes Related to Lung Function and Interstitial Lung Diseases Are Associated with Worse Outcomes in Severe COVID-19 and Lung Performance in the Post-COVID-19 Condition.International journal of molecular sciences · 2025Article
- Prior vaccination prevents overactivation of innate immune responses during COVID-19 breakthrough infection.Science translational medicine · 2025Article
- The interplay of tuberculosis and COVID-19: Insights into global health challenges.Journal of biosciences · 2025Review
74 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
42 authors at 6 institutions in 2 countries.
Marta Ferreira-Gomes *Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-7171-7952
Andrey Kruglov *Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Pawel Durek *Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Frederik Heinrich *Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Caroline Tizian *Laboratory of Innate Immunity, Department of Microbiology and Infection Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Gitta Anne Heinz *Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-9330-3689
Anna Pascual-ReguantDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-5042-3699
Weijie DuDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Ronja MothesDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Chaofan FanDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Stefan FrischbutterDermatological Allergology, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0003-3971-7343
Katharina HabenichtFriedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
Lisa BudzinskiDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0003-4120-6032
Justus NinnemannDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Peter K JaniDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Gabriela Maria GuerraDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Katrin LehmannDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Mareen MatzBIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
Lennard OstendorfDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0003-3553-6406
Lukas HeibergerDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Hyun-Dong ChangDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-7341-4533
Sandy BauherrDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-3736-3361
Marcus MaurerDermatological Allergology, Department of Dermatology and Allergy, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-4121-481X
Günther SchönrichInstitute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Martin RafteryInstitute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Tilmann KallinichDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Marcus Alexander MallBerlin Institute of Health (BIH), Berlin, Germany.ORCID http://orcid.org/0000-0002-4057-2199
Stefan AngermairDepartment of Anesthesiology and Intensive Care Medicine, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-5440-6968
Sascha TreskatschDepartment of Anesthesiology and Intensive Care Medicine, Campus Benjamin Franklin, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Thomas DörnerDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Victor Max CormanInstitute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0002-3605-0136
Andreas DiefenbachLaboratory of Innate Immunity, Department of Microbiology and Infection Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-9176-9530
Hans-Dieter VolkBIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.ORCID http://orcid.org/0000-0002-7743-6668
Sefer ElezkurtajInstitute of Pathology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Thomas H WinklerFriedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.ORCID http://orcid.org/0000-0002-1860-0528
Jun DongDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Anja Erika HauserDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0002-7725-9526
Helena RadbruchDepartment of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.ORCID http://orcid.org/0000-0001-6941-3397
Mario WitkowskiLaboratory of Innate Immunity, Department of Microbiology and Infection Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Fritz MelchersDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Andreas RadbruchDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.ORCID http://orcid.org/0000-0001-5753-0000
Mir-Farzin MashreghiDeutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany. mashreghi@drfz.de.ORCID http://orcid.org/0000-0002-8015-6907
Leibniz Association · DEHumboldt-Universität zu Berlin · DEGerman Rheumatism Research Centre · DEFriedrich-Alexander-Universität Erlangen-Nürnberg · DECharité - Universitätsmedizin Berlin · DEEngelhardt Institute of Molecular Biology · RU
Funding
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) COVID19-014 01KI2043A CoVER-AbEC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) ERC-2010-AdG.20100317 Grant 268978EC | European Regional Development Fund (Europski Fond za Regionalni Razvoj) ERDF 2014-2020, EFRE 1.8/11, Deutsches Rheuma-Forschungszentrum
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.
Indexed as
AdultAgedAged, 80 and overAntibodies, ViralCOVID-19FemaleHumansImmunoglobulin AImmunoglobulin GInterleukin-21InterleukinsMaleMiddle AgedPlasma CellsSARS-CoV-2Spike Glycoprotein, CoronavirusAntibodies, ViralImmunoglobulin AImmunoglobulin GInterleukin-21InterleukinsSpike Glycoprotein, Coronavirusspike protein, SARS-CoV-2Transforming Growth Factor beta
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