TY - JOUR
T1 - Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
AU - Deutsche COVID-19 Omics Initiative (DeCOI)
AU - Schulte-Schrepping, Jonas
AU - Reusch, Nico
AU - Paclik, Daniela
AU - Baßler, Kevin
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 - Gagneur, Julien
AU - Theis, Fabian
N1 - Publisher Copyright:
© 2020 Elsevier Inc.
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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.
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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.
KW - COVID-19
KW - SARS-CoV-2
KW - dysfunctional neutrophils
KW - emergency myelopoiesis
KW - immune profiling
KW - mass cytometry
KW - monocytes
KW - neutrophils
KW - scRNA-seq
UR - http://www.scopus.com/inward/record.url?scp=85089541366&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2020.08.001
DO - 10.1016/j.cell.2020.08.001
M3 - Article
C2 - 32810438
AN - SCOPUS:85089541366
SN - 0092-8674
VL - 182
SP - 1419-1440.e23
JO - Cell
JF - Cell
IS - 6
ER -