Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
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Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. / Schulte-Schrepping, Jonas; Reusch, Nico; Paclik, Daniela; Germany, Life and Medical Sciences (LIMES) Institute University of; 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; Raabe, Jan; Kaiser, Kim Melanie; Vinh, Michael To; Rieke, Gereon; Meisel, Christian; Ulas, Thomas; Becker, Matthias; Geffers, Robert; Witzenrath, Martin; Drosten, Christian; Suttorp, Norbert; von Kalle, Christof; Kurth, Florian; Händler, Kristian; Schultze, Joachim L; Aschenbrenner, Anna C; Li, Yang; Nattermann, Jacob; Sawitzki, Birgit; Saliba, Antoine-Emmanuel; Sander, Leif Erik; Deutsche COVID-19 OMICS Initiative (DeCOI).
in: CELL, Jahrgang 182, Nr. 6, 17.09.2020, S. 1419-1440.e23.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
AU - Schulte-Schrepping, Jonas
AU - Reusch, Nico
AU - Paclik, Daniela
AU - Germany, Life and Medical Sciences (LIMES) Institute University of
AU - Schlickeiser, Stephan
AU - Zhang, Bowen
AU - Krämer, Benjamin
AU - Krammer, Tobias
AU - Brumhard, Sophia
AU - Bonaguro, Lorenzo
AU - De Domenico, Elena
AU - Wendisch, Daniel
AU - Grasshoff, Martin
AU - Kapellos, Theodore S
AU - Beckstette, Michael
AU - Pecht, Tal
AU - Saglam, Adem
AU - Dietrich, Oliver
AU - Mei, Henrik E
AU - Schulz, Axel R
AU - Conrad, Claudia
AU - Kunkel, Désirée
AU - Vafadarnejad, Ehsan
AU - Xu, Cheng-Jian
AU - Horne, Arik
AU - Herbert, Miriam
AU - Drews, Anna
AU - Thibeault, Charlotte
AU - Pfeiffer, Moritz
AU - Hippenstiel, Stefan
AU - Hocke, Andreas
AU - Müller-Redetzky, Holger
AU - Heim, Katrin-Moira
AU - Machleidt, Felix
AU - Uhrig, Alexander
AU - Bosquillon de Jarcy, Laure
AU - Jürgens, Linda
AU - Stegemann, Miriam
AU - Glösenkamp, Christoph R
AU - Volk, Hans-Dieter
AU - Goffinet, Christine
AU - Landthaler, Markus
AU - Wyler, Emanuel
AU - Georg, Philipp
AU - Schneider, Maria
AU - Dang-Heine, Chantip
AU - Neuwinger, Nick
AU - Kappert, Kai
AU - Tauber, Rudolf
AU - Corman, Victor
AU - Raabe, Jan
AU - Kaiser, Kim Melanie
AU - Vinh, Michael To
AU - Rieke, Gereon
AU - Meisel, Christian
AU - Ulas, Thomas
AU - Becker, Matthias
AU - Geffers, Robert
AU - Witzenrath, Martin
AU - Drosten, Christian
AU - Suttorp, Norbert
AU - von Kalle, Christof
AU - Kurth, Florian
AU - Händler, Kristian
AU - Schultze, Joachim L
AU - Aschenbrenner, Anna C
AU - Li, Yang
AU - Nattermann, Jacob
AU - Sawitzki, Birgit
AU - Saliba, Antoine-Emmanuel
AU - Sander, Leif Erik
AU - Deutsche COVID-19 OMICS Initiative (DeCOI)
N1 - Copyright © 2020 Elsevier Inc. All rights reserved.
PY - 2020/9/17
Y1 - 2020/9/17
N2 - 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.
AB - 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.
KW - Adult
KW - Aged
KW - CD11 Antigens/genetics
KW - COVID-19
KW - Cells, Cultured
KW - Coronavirus Infections/blood
KW - Female
KW - HLA-DR Antigens/genetics
KW - Humans
KW - Male
KW - Middle Aged
KW - Myeloid Cells/cytology
KW - Myelopoiesis
KW - Pandemics
KW - Pneumonia, Viral/blood
KW - Proteome/genetics
KW - Proteomics
KW - Single-Cell Analysis
U2 - 10.1016/j.cell.2020.08.001
DO - 10.1016/j.cell.2020.08.001
M3 - SCORING: Journal article
C2 - 32810438
VL - 182
SP - 1419-1440.e23
JO - CELL
JF - CELL
SN - 0092-8674
IS - 6
ER -