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Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment #MMPMID32810438
Schulte-Schrepping J; Reusch N; Paclik D; Bassler K; Schlickeiser S; Zhang B; Kramer 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; Muller-Redetzky H; Heim KM; Machleidt F; Uhrig A; Bosquillon de Jarcy L; Jurgens L; Stegemann M; Glosenkamp 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; Handler K; Schultze JL; Aschenbrenner AC; Li Y; Nattermann J; Sawitzki B; Saliba AE; Sander LE
Cell 2020[Sep]; 182 (6): 1419-1440.e23 PMID32810438show ga
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-DR(hi)CD11c(hi) 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-DR(lo) 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.
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Cell 2020 ; 182 (6): 1419-1440.e23
