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.
- 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, 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.
- Muller-Redetzky, H.
- Heim, K. M.
- Machleidt, F.
- Uhrig, A.
- Bosquillon de Jarcy, L.
- Jurgens, L.
- Stegemann, M.
- Glosenkamp, 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.
- Handler, K.
- Schultze, J. L.
- Aschenbrenner, A. C.
- Li, Y.
- Nattermann, J.
- Sawitzki, B.
- Saliba, A. E.
- Sander, L. E.
- Deutsche, Covid-Omics Initiative
Keywords
- *covid-19
- *SARS-CoV-2
- *dysfunctional neutrophils
- *emergency myelopoiesis
- *immune profiling
- *mass cytometry
- *monocytes
- *neutrophils
- *scRNA-seq