Severe COVID-19 is marked by a dysregulated myeloid cell compartment

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

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.