Science and Research

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

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
Publication details
DOI: 10.1016/j.cell.2020.08.001
Journal: Cell
Pages: 1419-1440 e23 
Number: 6
Work Type: Original
Location: BIH
Disease Area: PALI
Partner / Member: Assoziierter Partner
Access-Number: 32810438
See publication on PubMed

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