J. Schulte-Schrepping, N. Reusch, D. Paclik, K. Baßler, S. Schlickeiser, Bowen Zhang, B. Krämer, T. Krammer, S. Brumhard, L. Bonaguro, E. De Domenico, D. Wendisch, M. Grasshoff, T. S. Kapellos, M. Beckstette, T. Pecht, A. Saglam, O. Dietrich, H. Mei, A. Schulz, C. Conrad, D. Kunkel, E. Vafadarnejad, C. Xu, A. Horne, M. Herbert, A. Drews, C. Thibeault, M. Pfeiffer, S. Hippenstiel, A. Hocke, H. Müller-Redetzky, K. Heim, F. Machleidt, A. Uhrig, L. Bosquillon de Jarcy, L. Jürgens, M. Stegemann, C. R. Glösenkamp, H. Volk, C. Goffinet, M. Landthaler, E. Wyler, P. Georg, M. Schneider, C. Dang-Heine, N. Neuwinger, K. Kappert, R. Tauber, V. Corman, J. Raabe, K. Kaiser, M. T. Vinh, G. Rieke, C. Meisel, T. Ulas, M. Becker, R. Geffers, M. Witzenrath, C. Drosten, N. Suttorp, C. von Kalle, F. Kurth, K. Händler, J. Schultze, A. Aschenbrenner, Y. Li, J. Nattermann, B. Sawitzki, A. Saliba, L. Sander, Angel Robert Alexander Anke Daniela Ezio Peer Thomas Mar Angelov Bals Bartholomäus Becker Bezdan Bonifacio , A. Angelov, R. Bals, Alexander Bartholomäus, A. Becker, D. Bezdan, E. Bonifacio, P. Bork, T. Clavel, M. Colomé-Tatché, A. Diefenbach, A. Dilthey, N. Fischer, K. Förstner, J. Frick, J. Gagneur, A. Goesmann, T. Hain, M. Hummel, Stefan Janssen, J. Kalinowski, R. Kallies, Birte Kehr, A. Keller, S. Kim-Hellmuth, C. Klein, O. Kohlbacher, J. Korbel, I. Kurth, M. Landthaler, Y. Li, K. Ludwig, O. Makarewicz, M. Marz, A. McHardy, Christian Mertes, M. Nöthen, P. Nürnberg, U. Ohler, S. Ossowski, J. Overmann, S. Peter, K. Pfeffer, A. Poetsch, A. Pühler, N. Rajewsky, M. Ralser, O. Riess, S. Ripke, U. Nunes da Rocha, P. Rosenstiel, A. Saliba, L. Sander, B. Sawitzki, Philipp H. Schiffer, E. Schulte, J. Schultze, A. Sczyrba, O. Stegle, J. Stoye, F. Theis, J. Vehreschild, J. Vogel, M. von Kleist, A. Walker, J. Walter, D. Wieczorek, J. Ziebuhr
Cell, 2020
Summary 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.
Cited by 305 publications.
Field of study: Biology