Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment

Autor: Stephan Schlickeiser, Chantip Dang-Heine, Florian Kurth, Jonas Schulte-Schrepping, Christoph R. Glösenkamp, Moritz Pfeiffer, Michael Hummel, Christof von Kalle, Christian Meisel, Oliver Dietrich, Philipp Georg, Nikolaus Rajewsky, Nicole Fischer, Stephan Ripke, Peter Nürnberg, Daniela Paclik, Miriam Herbert, Alexander Goesmann, Maria Schneider, Kevin Baßler, Andreas Keller, Daniela Bezdan, Ulisses Nunes da Rocha, Ingo Kurth, Torsten Hain, Eva-Christina Schulte, Andreas Walker, Thomas Ulas, Laure Bosquillon de Jarcy, Oliver Stegle, Alexander Bartholomäus, Holger Müller-Redetzky, Ezio Bonifacio, Markus Ralser, Nick Neuwinger, Manja Marz, Désirée Kunkel, Alexander Uhrig, Uwe Ohler, Antoine-Emmanuel Saliba, Axel Schulz, Markus Landthaler, Michael To Vinh, Alexander Sczyrba, Emanuel Wyler, Philip Rosenstiel, Jan O. Korbel, Thomas Clavel, Tobias Krammer, Elena De Domenico, Gereon Rieke, Christian Drosten, Silke Peter, Martin Witzenrath, Victor M. Corman, Kerstin U. Ludwig, Linda Jürgens, Michael Beckstette, Kim Melanie Kaiser, Birte Kehr, Jens Stoye, Christoph Klein, Olaf Rieß, Charlotte Thibeault, Robert Bals, Sophia Brumhard, Robert Geffers, Alice C. McHardy, Anna C. Aschenbrenner, Kai Kappert, Jörg Vogel, Dagmar Wieczorek, Alexander T. Dilthey, Yang Li, Andreas C. Hocke, Hans-Dieter Volk, Janne Vehreschild, Sarah Kim-Hellmuth, Benjamin Krämer, Maria Colomé-Tatché, Stephan Ossowski, Julien Gagneur, Martin Grasshoff, Alfred Pühler, Philipp H. Schiffer, René Kallies, Oliwia Makarewicz, Adem Saglam, Nico Reusch, Julia-Stefanie Frick, Angel Angelov, Jan Raabe, Andreas Diefenbach, Markus M. Nöthen, Daniel Wendisch, Fabian J. Theis, John Ziebuhr, Christian Mertes, Theodore S. Kapellos, Henrik E. Mei, Stefan Janssen, Claudia Conrad, Leif E. Sander, Klaus Pfeffer, Felix Machleidt, Anke Becker, Anna R. Poetsch, Arik Horne, Rudolf Tauber, Max von Kleist, Jörg Overmann, Kristian Händler, Katrin-Moira Heim, Joachim L. Schultze, Matthias Becker, Lorenzo Bonaguro, Cheng-Jian Xu, Jörn Kalinowski, Anna Drews, Tal Pecht, Stefan Hippenstiel, Konrad U. Förstner, Ehsan Vafadarnejad, Bowen Zhang, Oliver Kohlbacher, Peer Bork, Jacob Nattermann, Norbert Suttorp, Birgit Sawitzki, Jörn Walter, Christine Goffinet, Miriam Stegemann
Přispěvatelé: BRICS, Braunschweiger Zentrum für Systembiologie, Rebenring 56,38106 Braunschweig, Germany., HIRI, Helmholtz-Institut für RNA-basierte Infektionsforschung, Josef-Shneider Strasse 2, 97080 Würzburg, Germany., CiiM, Zentrum für individualisierte Infektionsmedizin, Feodor-Lynen-Str.7, 30625 Hannover., HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Rok vydání: 2020
Předmět:
Male
Proteomics
metabolism [CD11 Antigens]
Myeloid
Proteome
Pathogenesis
0302 clinical medicine
neutrophils
immunology [Coronavirus Infections]
Myeloid Cells
blood [Coronavirus Infections]
Cells
Cultured
Myelopoiesis
0303 health sciences
immune profiling
Middle Aged
3. Good health
medicine.anatomical_structure
genetics [Proteome]
Female
genetics [HLA-DR Antigens]
Single-Cell Analysis
monocytes
Coronavirus Infections
mass cytometry
Adult
Pneumonia
Viral
Biology
genetics [CD11 Antigens]
Peripheral blood mononuclear cell
General Biochemistry
Genetics and Molecular Biology
Article
03 medical and health sciences
Immune system
dysfunctional neutrophils
scRNA-seq
medicine
Humans
ddc:610
Pandemics
030304 developmental biology
Aged
immunology [Pneumonia
Viral]
SARS-CoV-2
CD11 Antigens
pathology [Pneumonia
Viral]
COVID-19
emergency myelopoiesis
HLA-DR Antigens
metabolism [Proteome]
Gene signature
pathology [Coronavirus Infections]
metabolism [HLA-DR Antigens]
blood [Pneumonia
Viral]
Respiratory failure
cytology [Myeloid Cells]
Immunology
030217 neurology & neurosurgery
immunology [Myeloid Cells]
Respiratory tract
Zdroj: Cell
1440.e23
United States
Cell 182(6), 1419-1440.e23 (2020). doi:10.1016/j.cell.2020.08.001
ISSN: 0092-8674
DOI: 10.1016/j.cell.2020.08.001
Popis: Summary Coronavirus Disease 2019 (COVID-19) is a mild to moderate respiratory tract infection, however, a subset of patients progresses 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, remains 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 vs. 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 it reveals profound alterations in the myeloid cell compartment associated with severe COVID-19.
Highlights ● SARS-CoV-2 infection induces profound alterations of the myeloid compartment ● Mild COVID-19 is marked by inflammatory HLA-DRhiCD11chi CD14+ monocytes ● Dysfunctional HLA-DRloCD163hi and HLA-DRloS100Ahi CD14+ monocytes in severe COVID-19 ● Emergency myelopoiesis with immature and dysfunctional neutrophils in severe COVID-19
Databáze: OpenAIRE
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