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

• Published in: Cell Vol. 182; no. 6; pp. 1419 - 1440.e23
• Main Authors: Schulte-Schrepping, Jonas, Reusch, Nico, Paclik, Daniela, Baßler, Kevin, Schlickeiser, Stephan, Krammer, Tobias, Brumhard, Sophia, Bonaguro, Lorenzo, Wendisch, Daniel, Grasshoff, Martin, Beckstette, Michael, Pecht, Tal, Saglam, Adem, Dietrich, Oliver, Mei, Henrik E., Schulz, Axel R., Conrad, Claudia, Kunkel, Désirée, Vafadarnejad, Ehsan, Xu, Cheng-Jian, Herbert, Miriam, Drews, Anna, Thibeault, Charlotte, Pfeiffer, Moritz, Hippenstiel, Stefan, Hocke, Andreas, Müller-Redetzky, Holger, Heim, Katrin-Moira, Bosquillon de Jarcy, Laure, Stegemann, Miriam, Glösenkamp, Christoph R., Volk, Hans-Dieter, Wyler, Emanuel, Georg, Philipp, Schneider, Maria, Dang-Heine, Chantip, Neuwinger, Nick, Kappert, Kai, Corman, Victor, Raabe, Jan, Kaiser, Kim Melanie, Rieke, Gereon, Meisel, Christian, Ulas, Thomas, Becker, Matthias, Drosten, Christian, Suttorp, Norbert, Kurth, Florian, Schultze, Joachim L., Aschenbrenner, Anna C., Li, Yang, Nattermann, Jacob, Saliba, Antoine-Emmanuel, Sander, Leif Erik, Angelov, Angel, Bals, Robert, Bartholomäus, Alexander, Becker, Anke, Bonifacio, Ezio, Clavel, Thomas, Colome-Tatche, Maria, Diefenbach, Andreas, Dilthey, Alexander, Fischer, Nicole, Förstner, Konrad, Hain, Torsten, Hummel, Michael, Janssen, Stefan, Kallies, René, Kehr, Birte, Keller, Andreas, Kim-Hellmuth, Sarah, Klein, Christoph, Korbel, Jan O., Landthaler, Markus, Ludwig, Kerstin, Marz, Manja, McHardy, Alice, Mertes, Christian, Nöthen, Markus, Nürnberg, Peter, Ohler, Uwe, Ossowski, Stephan, Overmann, Jörg, Peter, Silke, Pfeffer, Klaus, Rajewsky, Nikolaus, Ralser, Markus, Schulte, Eva-Christina, Sczyrba, Alexander, Stoye, Jens, Theis, Fabian, Vogel, Jörg, von Kleist, Max, Walker, Andreas, Walter, Jörn, Wieczorek, Dagmar
• Format: Journal Article Web Resource
• Language: English
• Published: United States Elsevier Inc 17.09.2020; Elsevier BV
• Subjects: Adult; Aged; CD11 Antigens - genetics; CD11 Antigens - metabolism; Cells, Cultured; Coronavirus Infections - blood; Coronavirus Infections - immunology; Coronavirus Infections - pathology; COVID-19; dysfunctional neutrophils; emergency myelopoiesis; Female; HLA-DR Antigens - genetics; HLA-DR Antigens - metabolism; Humans; immune profiling; Male; mass cytometry; Middle Aged; monocytes; Myeloid Cells - cytology; Myeloid Cells - immunology; Myelopoiesis; neutrophils; Pandemics; Pneumonia, Viral - blood; Pneumonia, Viral - immunology; Pneumonia, Viral - pathology; Proteome - genetics; Proteome - metabolism; Proteomics; SARS-CoV-2; scRNA-seq; Single-Cell Analysis; COVID-19; monocytes; SARS-CoV-2; scRNA-seq; emergency myelopoiesis; immune profiling; dysfunctional neutrophils; mass cytometry; neutrophils
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/j.cell.2020.08.001

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. [Display omitted] •SARS-CoV-2 infection induces profound alterations of the myeloid compartment•Mild COVID-19 is marked by inflammatory HLA-DRhiCD11chi CD14+ monocytes•Dysfunctional HLA-DRloCD163hi and HLA-DRloS100Ahi CD14+ monocytes in severe COVID-19•Emergency myelopoiesis with immature and dysfunctional neutrophils in 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.