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 cou...

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Detalles Bibliográficos
Autores principales: Schulte-Schrepping, Jonas, Reusch, Nico, Paclik, Daniela, Baßler, Kevin, Schlickeiser, Stephan, Zhang, Bowen, Krämer, 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, Désirée, Vafadarnejad, Ehsan, Xu, Cheng-Jian, Horne, Arik, Herbert, Miriam, Drews, Anna, Thibeault, Charlotte, Pfeiffer, Moritz, Hippenstiel, Stefan, Hocke, Andreas, Müller-Redetzky, Holger, Heim, Katrin-Moira, Machleidt, Felix, Uhrig, Alexander, Bosquillon de Jarcy, Laure, Jürgens, Linda, Stegemann, Miriam, Glösenkamp, 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, Händler, Kristian, Schultze, Joachim L., Aschenbrenner, Anna C., Li, Yang, Nattermann, Jacob, Sawitzki, Birgit, Saliba, Antoine-Emmanuel, Sander, Leif Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2020
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405822/
https://www.ncbi.nlm.nih.gov/pubmed/32810438
http://dx.doi.org/10.1016/j.cell.2020.08.001
Descripción
Sumario: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.

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