학술논문
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
Document Type
Report
Author
Schulte-Schrepping, Jonas; Reusch, Nico; Paclik, Daniela; Ba[sz]ler, Kevin; Schlickeiser, Stephan; Zhang, Bowen; Kramer, Benjamin; Krammer, Tobias; Brumhard, Sophia; Bonaguro, Lorenzo; De Domenico, Elena; Wendisch, Daniel; Grasshoff, Martin; Kapellos, Theodore S.; Beckstette, Michael; Pecht, Tal; Saglam, Adem; Dietrich, Oliver; Mei, Henrik E.; Schulz, Axel R.; Conrad, Claudia; Kunkel, Desiree; Vafadarnejad, Ehsan; Xu, Cheng-Jian; Horne, Arik; Herbert, Miriam; Drews, Anna; Thibeault, Charlotte; Pfeiffer, Moritz; Hippenstiel, Stefan; Hocke, Andreas; Muller-Redetzky, Holger; Heim, Katrin-Moira; Machleidt, Felix; Uhrig, Alexander; Bosquillon de Jarcy, Laure; Jurgens, Linda; Stegemann, Miriam; Glosenkamp, Christoph R.; Volk, Hans-Dieter; Goffinet, Christine; Landthaler, Markus; Wyler, Emanuel; Georg, Philipp; Schneider, Maria; Dang-Heine, Chantip; Neuwinger, Nick; Kappert, Kai; Tauber, Rudolf; Corman, Victor; Raabe, Jan; Kaiser, Kim Melanie; Vinh, Michael To; Rieke, Gereon; Meisel, Christian; Ulas, Thomas; Becker, Matthias; Geffers, Robert; Witzenrath, Martin; Drosten, Christian; Suttorp, Norbert; von Kalle, Christof; Kurth, Florian; Handler, Kristian; Schultze, Joachim L.; Aschenbrenner, Anna C.; Li, Yang; Nattermann, Jacob; Sawitzki, Birgit; Saliba, Antoine-Emmanuel; Sander, Leif Erik; Angelov, Angel; Bals, Robert; Bartholomaus, Alexander; Becker, Anke; Bezdan, Daniela; Bonifacio, Ezio; Bork, Peer; Clavel, Thomas; Colome-Tatche, Maria; Diefenbach, Andreas; Dilthey, Alexander; Fischer, Nicole; Forstner, Konrad; Frick, Julia-Stefanie; Gagneur, Julien; Goesmann, Alexander; Hain, Torsten; Hummel, Michael; Janssen, Stefan; Kalinowski, Jorn; Kallies, Rene; Kehr, Birte; Keller, Andreas; Kim-Hellmuth, Sarah; Klein, Christoph; Kohlbacher, Oliver; Korbel, Jan O.; Kurth, Ingo; Ludwig, Kerstin; Makarewicz, Oliwia; Marz, Manja; McHardy, Alice; Mertes, Christian; Nothen, Markus; Nurnberg, Peter; Ohler, Uwe; Ossowski, Stephan; Overmann, Jorg; Peter, Silke; Pfeffer, Klaus; Poetsch, Anna R.; Puhler, Alfred; Rajewsky, Nikolaus; Ralser, Markus; Rie[sz], Olaf; Ripke, Stephan; Nunes da Rocha, Ulisses; Rosenstiel, Philip; Schiffer, Philipp; Schulte, Eva-Christina; Sczyrba, Alexander; Stegle, Oliver; Stoye, Jens; Theis, Fabian; Vehreschild, Janne; Vogel, Jorg; von Kleist, Max; Walker, Andreas; Walter, Jorn; Wieczorek, Dagmar; Ziebuhr, John
Source
Cell. Sept 17, 2020, Vol. 182 Issue 6, 1419
Subject
Language
English
ISSN
0092-8674
Abstract
Keywords COVID-19; SARS-CoV-2; monocytes; neutrophils; dysfunctional neutrophils; emergency myelopoiesis; immune profiling; scRNA-seq; mass cytometry Highlights * SARS-CoV-2 infection induces profound alterations of the myeloid compartment * Mild COVID-19 is marked by inflammatory HLA-DR.sup.hiCD11c.sup.hi CD14.sup.+ monocytes * Dysfunctional HLA-DR.sup.loCD163.sup.hi and HLA-DR.sup.loS100A.sup.hi CD14.sup.+ monocytes in severe COVID-19 * Emergency myelopoiesis with immature and dysfunctional neutrophils in severe COVID-19 Summary 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.sup.hiCD11c.sup.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.sup.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.