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

Schulte-Schrepping J, Reusch N, Paclik D, Bassler K, Schlickeiser S, Zhang B, Kraemer B, Krammer T, Brumhard S, Bonaguro L, De Domenico E, Wendisch D, Grasshoff M, Kapellos TS, Beckstette M, Pecht T, Saglam A, Dietrich O, Mei HE, Schulz AR, Conrad C, Kunkel D, Vafadarnejad E, Xu CJ, Horne A, Herbert M, Drews A, Thibeault C, Pfeiffer M, Hippenstiel S, Hocke A, Mueller-Redetzky H, Heim KM, Machleidt F, Uhrig A, De Jarcy LB, Juergens L, Stegemann M, Gloesenkamp CR, Volk HD, Goffinet C, Landthaler M, Wyler E, Georg P, Schneider M, Dang-Heine C, Neuwinger N, Kappert K, Tauber R, Corman V, Raabe J, Kaiser KM, Vinh MT, Rieke G, Meisel C, Ulas T, Becker M, Geffers R, Witzenrath M, Drosten C, Suttorp N, Von Kalle C, Kurth F, Haendler K, Schultze JL, Aschenbrenner AC, Li Y, Nattermann J, Sawitzki B, Saliba AE, Sander LE (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Cell Elsevier

Book Volume: 182

Pages Range: 1419-1440.e23

Journal Issue: 6

DOI: 10.1016/j.cell.2020.08.001

Abstract

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.

Involved external institutions

Rheinische Friedrich-Wilhelms-Universität Bonn DE Germany (DE) Charité - Universitätsmedizin Berlin DE Germany (DE) Zentrum für Individualisierte Infektionsmedizin (CiiM) DE Germany (DE) Universitätsklinikum Bonn DE Germany (DE) Helmholtz-Zentrum für Infektionsforschung (HZI) DE Germany (DE) Labor Berlin – Charité Vivantes GmbH DE Germany (DE) Deutsches Rheuma-Forschungszentrum (DRFZ) DE Germany (DE) Berliner Institut für Gesundheitsforschung (BIH) DE Germany (DE) Max-Delbrück-Centrum für Molekulare Medizin / Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch DE Germany (DE)

How to cite

APA:

Schulte-Schrepping, J., Reusch, N., Paclik, D., Bassler, K., Schlickeiser, S., Zhang, B.,... Sander, L.E. (2020). Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell, 182(6), 1419-1440.e23. https://doi.org/10.1016/j.cell.2020.08.001

MLA:

Schulte-Schrepping, Jonas, et al. "Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment." Cell 182.6 (2020): 1419-1440.e23.

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