Severe COVID-19 is marked by a dysregulated myeloid cell compartment

Item Type:	Article
Title:	Severe COVID-19 is marked by a dysregulated myeloid cell compartment
Creators Name:	Schulte-Schrepping, J. and Reusch, N. and Paclik, D. and Baßler, K. and Schlickeiser, S. and Zhang, B. and Krämer, B. and Krammer, T. and Brumhard, S. and Bonaguro, L. and De Domenico, E. and Wendisch, Da. and Grasshoff, M. and Kapellos, T.S. and Beckstette, M. and Pecht, T. and Saglam, A. and Dietrich, O. and Mei, H.E. and Schulz, A.R. and Conrad, C. and Kunkel, D. and Vafadarnejad, E. and Xu, C.J. and Horne, A. and Herbert, M. and Drews, A. and Thibeault, C. and Pfeiffer, M. and Hippenstiel, S. and Hocke, A. and Müller-Redetzky, H. and Heim, K.M. and Machleidt, F. and Uhrig, A. and Bosquillon de Jarcy, L. and Jürgens, L. and Stegemann, M. and Glösenkamp, C.R. and Volk, H.D. and Goffinet, C. and Landthaler, M. and Wyler, E. and Georg, P. and Schneider, M. and Dang-Heine, C. and Neuwinger, N. and Kappert, K. and Tauber, R. and Corman, V. and Raabe, J. and Kaiser, K.M. and Vinh, M.T. and Rieke, G. and Meisel, C. and Ulas, T. and Becker, M. and Geffers, R. and Witzenrath, M. and Drosten, C. and Suttorp, N. and von Kalle, C. and Kurth, F. and Händler, K. and Schultze, J.L. and Aschenbrenner, A.C. and Li, Y. and Nattermann, J. and Sawitzki, B. and Saliba, A.E. and Sander, L.E.
Abstract:	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.
Keywords:	COVID-19, SARS-CoV-2, Monocytes, Neutrophils, Dysfunctional Neutrophils, Emergency Myelopoiesis, Immune Profiling, scRNA-seq, Mass Cytometry
Source:	Cell
ISSN:	0092-8674
Publisher:	Cell Press
Volume:	182
Number:	6
Page Range:	1419-1440
Date:	17 September 2020
Additional Information:	Markus Landthaler, Uwe Ohler, and Nikolaus Rajewsky are members of the Deutsche COVID-19 Omics Initiative (DeCOI).
Official Publication:	https://doi.org/10.1016/j.cell.2020.08.001
External Fulltext:	View full text on PubMed Central
PubMed:	View item in PubMed

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