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SARS-CoV-2 in severe COVID-19 induces a TGF-ß-dominated chronic immune response that does not target itself.
Ferreira-Gomes, Marta; Kruglov, Andrey; Durek, Pawel; Heinrich, Frederik; Tizian, Caroline; Heinz, Gitta Anne; Pascual-Reguant, Anna; Du, Weijie; Mothes, Ronja; Fan, Chaofan; Frischbutter, Stefan; Habenicht, Katharina; Budzinski, Lisa; Ninnemann, Justus; Jani, Peter K; Guerra, Gabriela Maria; Lehmann, Katrin; Matz, Mareen; Ostendorf, Lennard; Heiberger, Lukas; Chang, Hyun-Dong; Bauherr, Sandy; Maurer, Marcus; Schönrich, Günther; Raftery, Martin; Kallinich, Tilmann; Mall, Marcus Alexander; Angermair, Stefan; Treskatsch, Sascha; Dörner, Thomas; Corman, Victor Max; Diefenbach, Andreas; Volk, Hans-Dieter; Elezkurtaj, Sefer; Winkler, Thomas H; Dong, Jun; Hauser, Anja Erika; Radbruch, Helena; Witkowski, Mario; Melchers, Fritz; Radbruch, Andreas; Mashreghi, Mir-Farzin.
  • Ferreira-Gomes M; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Kruglov A; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Durek P; Belozersky Institute of Physico-Chemical Biology and Biological Faculty, M.V. Lomonosov Moscow State University, Moscow, Russia.
  • Heinrich F; Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, Moscow, Russia.
  • Tizian C; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Heinz GA; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Pascual-Reguant A; Laboratory of Innate Immunity, Department of Microbiology and Infection Immunology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
  • Du W; Berlin Institute of Health (BIH), Berlin, Germany.
  • Mothes R; Mucosal and Developmental Immunology, Deutsches Rheuma-Forschungszentrum, Berlin, Germany.
  • Fan C; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Frischbutter S; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Habenicht K; Department of Rheumatology and Clinical Immunology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Budzinski L; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Ninnemann J; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Jani PK; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Guerra GM; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Lehmann K; Dermatological 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.
  • Matz M; Friedrich-Alexander-University Erlangen-Nuremberg, Erlangen, Germany.
  • Ostendorf L; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Heiberger L; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Chang HD; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Bauherr S; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Maurer M; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Schönrich G; BIH Center for Regenerative Therapies (BCRT), Charité Universitätsmedizin Berlin, Berlin, Germany.
  • Raftery M; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Kallinich T; Department of Neuropathology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Mall MA; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Angermair S; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Treskatsch S; Technische Universität Berlin, Institute of Biotechnology, Berlin, Germany.
  • Dörner T; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Corman VM; Dermatological 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.
  • Diefenbach A; Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Volk HD; Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Elezkurtaj S; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
  • Winkler TH; Berlin Institute of Health (BIH), Berlin, Germany.
  • Dong J; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Hauser AE; Berlin Institute of Health (BIH), Berlin, Germany.
  • Radbruch H; Department of Pediatric Pulmonology, Immunology and Critical Care Medicine, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Witkowski M; German Centre for Lung Research (DZL), associated partner site, Berlin, Germany.
  • Melchers F; Department 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.
  • Radbruch A; Department 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.
  • Mashreghi MF; Deutsches Rheuma-Forschungszentrum (DRFZ), an Institute of the Leibniz Association, Berlin, Germany.
Nat Commun ; 12(1): 1961, 2021 03 30.
Article in English | MEDLINE | ID: covidwho-1169399
Semantic information from SemMedBD (by NLM)
1. 2019 novel coronavirus COEXISTS_WITH COVID-19
Subject
2019 novel coronavirus
Predicate
COEXISTS_WITH
Object
COVID-19
2. 2019 novel coronavirus CAUSES Immune response
Subject
2019 novel coronavirus
Predicate
CAUSES
Object
Immune response
3. COVID-19 COEXISTS_WITH Immune
Subject
COVID-19
Predicate
COEXISTS_WITH
Object
Immune
4. Cells PART_OF Unmarried person
Subject
Cells
Predicate
PART_OF
Object
Unmarried person
5. COVID-19 PROCESS_OF Patients
Subject
COVID-19
Predicate
PROCESS_OF
Object
Patients
6. Adaptive Immune Response PROCESS_OF Patients
Subject
Adaptive Immune Response
Predicate
PROCESS_OF
Object
Patients
7. Transforming Growth Factor beta STIMULATES spike protei
Subject
Transforming Growth Factor beta
Predicate
STIMULATES
Object
spike protei
8. interleukin-21 STIMULATES spike protei
Subject
interleukin-21
Predicate
STIMULATES
Object
spike protei
9. IgA2 PART_OF Patients
Subject
IgA2
Predicate
PART_OF
Object
Patients
10. Lung PART_OF Patients
Subject
Lung
Predicate
PART_OF
Object
Patients
11. Lung NEG_LOCATION_OF Blood
Subject
Lung
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NEG_LOCATION_OF
Object
Blood
12. IgA2 INTERACTS_WITH Antigens
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IgA2
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INTERACTS_WITH
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Antigens
13. Antigens PART_OF 2019 novel coronavirus
Subject
Antigens
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PART_OF
Object
2019 novel coronavirus
14. 2019 novel coronavirus COEXISTS_WITH COVID-19
Subject
2019 novel coronavirus
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COEXISTS_WITH
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COVID-19
15. 2019 novel coronavirus CAUSES Immune response
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2019 novel coronavirus
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CAUSES
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Immune response
16. COVID-19 COEXISTS_WITH Immune
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COVID-19
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COEXISTS_WITH
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Immune
17. Cells PART_OF Unmarried person
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COVID-19
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PROCESS_OF
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Patients
19. Adaptive Immune Response PROCESS_OF Patients
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Adaptive Immune Response
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PROCESS_OF
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Patients
20. Transforming Growth Factor beta STIMULATES spike protein, SARS-CoV-2
Subject
Transforming Growth Factor beta
Predicate
STIMULATES
Object
spike protein, SARS-CoV-2
21. interleukin-21 STIMULATES spike protein, SARS-CoV-2
Subject
interleukin-21
Predicate
STIMULATES
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spike protein, SARS-CoV-2
22. IgA2 PART_OF Patients
Subject
IgA2
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PART_OF
Object
Patients
23. Lung PART_OF Patients
Subject
Lung
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PART_OF
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Patients
24. Lung NEG_LOCATION_OF Blood
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Lung
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NEG_LOCATION_OF
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Blood
25. IgA2 INTERACTS_WITH Antigens
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IgA2
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INTERACTS_WITH
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Antigens
26. Antigens PART_OF 2019 novel coronavirus
Subject
Antigens
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PART_OF
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2019 novel coronavirus
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-ß, 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-ß. 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-ß, and is distracted from itself.
Subject(s)

Full text: Available Collection: International databases Database: MEDLINE Main subject: Transforming Growth Factor beta / SARS-CoV-2 / COVID-19 / Antibodies, Viral Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-22210-3

Full text: Available Collection: International databases Database: MEDLINE Main subject: Transforming Growth Factor beta / SARS-CoV-2 / COVID-19 / Antibodies, Viral Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Nat Commun Journal subject: Biology / Science Year: 2021 Document Type: Article Affiliation country: S41467-021-22210-3