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

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Item Type:	Article
Title:	Severe COVID-19 is marked by a dysregulated myeloid cell compartment
Creators Name:	Schulte-Schrepping, J., Reusch, N., Paclik, D., Baßler, K., Schlickeiser, S., Zhang, B., Krämer, B., Krammer, T., Brumhard, S., Bonaguro, L., De Domenico, E., Wendisch, Da., Grasshoff, M., Kapellos, T.S., Beckstette, M., Pecht, T., Saglam, A., Dietrich, O., Mei, H.E., Schulz, A.R., Conrad, C., Kunkel, D., Vafadarnejad, E., Xu, C.J., Horne, A., Herbert, M., Drews, A., Thibeault, C., Pfeiffer, M., Hippenstiel, S., Hocke, A., Müller-Redetzky, H., Heim, K.M., Machleidt, F., Uhrig, A., Bosquillon de Jarcy, L., Jürgens, L., Stegemann, M., Glösenkamp, C.R., Volk, H.D., Goffinet, C., Landthaler, M., Wyler, E., Georg, P., Schneider, M., Dang-Heine, C., Neuwinger, N., Kappert, K., Tauber, R., Corman, V., Raabe, J., Kaiser, K.M., Vinh, M.T., Rieke, G., Meisel, C., Ulas, T., Becker, M., Geffers, R., Witzenrath, M., Drosten, C., Suttorp, N., von Kalle, C., Kurth, F., Händler, K., Schultze, J.L., Aschenbrenner, A.C., Li, Y., Nattermann, J., Sawitzki, B., 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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