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Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment.
Schulte-Schrepping, Jonas; Reusch, Nico; Paclik, Daniela; Baßler, Kevin; Schlickeiser, Stephan; Zhang, Bowen; Krämer, Benjamin; Krammer, Tobias; Brumhard, Sophia; Bonaguro, Lorenzo; De Domenico, Elena; Wendisch, Daniel; Grasshoff, Martin; Kapellos, Theodore S; Beckstette, Michael; Pecht, Tal; Saglam, Adem; Dietrich, Oliver; Mei, Henrik E; Schulz, Axel R; Conrad, Claudia; Kunkel, Désirée; Vafadarnejad, Ehsan; Xu, Cheng-Jian; Horne, Arik; Herbert, Miriam; Drews, Anna; Thibeault, Charlotte; Pfeiffer, Moritz; Hippenstiel, Stefan; Hocke, Andreas; Müller-Redetzky, Holger; Heim, Katrin-Moira; Machleidt, Felix; Uhrig, Alexander; Bosquillon de Jarcy, Laure; Jürgens, Linda; Stegemann, Miriam; Glösenkamp, Christoph R; Volk, Hans-Dieter; Goffinet, Christine; Landthaler, Markus; Wyler, Emanuel; Georg, Philipp; Schneider, Maria; Dang-Heine, Chantip; Neuwinger, Nick; Kappert, Kai; Tauber, Rudolf; Corman, Victor.
  • Schulte-Schrepping J; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Reusch N; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Paclik D; Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Baßler K; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Schlickeiser S; Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH) Berlin, Germany.
  • Zhang B; Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Krämer B; Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
  • Krammer T; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.
  • Brumhard S; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Bonaguro L; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • De Domenico E; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
  • Wendisch D; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Grasshoff M; Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Kapellos TS; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Beckstette M; Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
  • Pecht T; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Saglam A; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
  • Dietrich O; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.
  • Mei HE; Mass Cytometry Lab, DRFZ Berlin, a Leibniz Institute, Berlin, Germany.
  • Schulz AR; Mass Cytometry Lab, DRFZ Berlin, a Leibniz Institute, Berlin, Germany.
  • Conrad C; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Kunkel D; Flow and Mass Cytometry Core Facility, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
  • Vafadarnejad E; Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.
  • Xu CJ; Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical
  • Horne A; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Herbert M; Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
  • Drews A; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
  • Thibeault C; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Pfeiffer M; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Hippenstiel S; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL).
  • Hocke A; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL).
  • Müller-Redetzky H; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Heim KM; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Machleidt F; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Uhrig A; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Bosquillon de Jarcy L; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Jürgens L; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Stegemann M; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Glösenkamp CR; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Volk HD; Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH) Berlin, Germany; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany.
  • Goffinet C; Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
  • Landthaler M; Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
  • Wyler E; Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
  • Georg P; Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Schneider M; Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Dang-Heine C; Clinical Study Center (CSC), Charité, Universitätsmedizin Berlin, and Berlin Institute of Health, Berlin, Germany.
  • Neuwinger N; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Kappert K; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Tauber R; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité, Universitätsmedizin Berlin, Berlin, Germany.
  • Corman V; Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany.
Cell ; 182(6): 1419-1440.e23, 2020 09 17.
Article in English | MEDLINE | ID: covidwho-694631
ABSTRACT
Coronavirus disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progress to severe disease and respiratory failure. The mechanism of protective immunity in mild forms and the pathogenesis of severe COVID-19 associated with increased neutrophil counts and dysregulated immune responses remain unclear. In a dual-center, two-cohort study, we combined single-cell RNA-sequencing and single-cell proteomics of whole-blood and peripheral-blood mononuclear cells to determine changes in immune cell composition and activation in mild versus severe COVID-19 (242 samples from 109 individuals) over time. HLA-DRhiCD11chi inflammatory monocytes with an interferon-stimulated gene signature were elevated in mild COVID-19. Severe COVID-19 was marked by occurrence of neutrophil precursors, as evidence of emergency myelopoiesis, dysfunctional mature neutrophils, and HLA-DRlo monocytes. Our study provides detailed insights into the systemic immune response to SARS-CoV-2 infection and reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Myeloid Cells / Myelopoiesis Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.08.001

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Pneumonia, Viral / Coronavirus Infections / Myeloid Cells / Myelopoiesis Type of study: Cohort study / Observational study / Prognostic study Limits: Adult / Aged / Female / Humans / Male / Middle aged Language: English Journal: Cell Year: 2020 Document Type: Article Affiliation country: J.cell.2020.08.001