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

Cell. 2020 Sep 17;182(6):1419-1440.e23. doi: 10.1016/j.cell.2020.08.001. | PubMed

Jonas Schulte-Schrepping¹, Nico Reusch¹, Daniela Paclik², Kevin Baßler¹, Stephan Schlickeiser³, Bowen Zhang⁴, Benjamin Krämer⁵, Tobias Krammer⁶, Sophia Brumhard⁷, Lorenzo Bonaguro¹, Elena De Domenico⁸, Daniel Wendisch⁷, Martin Grasshoff⁴, Theodore S Kapellos¹, Michael Beckstette⁴, Tal Pecht¹, Adem Saglam⁸, Oliver Dietrich⁶, Henrik E Mei⁹, Axel R Schulz⁹, Claudia Conrad⁷, Désirée Kunkel¹⁰, Ehsan Vafadarnejad⁶, Cheng-Jian Xu¹¹, Arik Horne¹, Miriam Herbert¹, Anna Drews⁸, Charlotte Thibeault⁷, Moritz Pfeiffer⁷, Stefan Hippenstiel¹², Andreas Hocke¹², Holger Müller-Redetzky⁷, Katrin-Moira Heim⁷, Felix Machleidt⁷, Alexander Uhrig⁷, Laure Bosquillon de Jarcy⁷, Linda Jürgens⁷, Miriam Stegemann⁷, Christoph R Glösenkamp⁷, Hans-Dieter Volk¹³, Christine Goffinet¹⁴, Markus Landthaler¹⁵, Emanuel Wyler¹⁵, Philipp Georg⁷, Maria Schneider², Chantip Dang-Heine¹⁶, Nick Neuwinger¹⁷, Kai Kappert¹⁷, Rudolf Tauber¹⁷, Victor Corman¹⁸, Jan Raabe⁵, Kim Melanie Kaiser⁵, Michael To Vinh⁵, Gereon Rieke⁵, Christian Meisel¹⁹, Thomas Ulas⁸, Matthias Becker⁸, Robert Geffers²⁰, Martin Witzenrath¹², Christian Drosten²¹, Norbert Suttorp¹², Christof von Kalle¹⁶, Florian Kurth²², Kristian Händler⁸, Joachim L Schultze²³, Anna C Aschenbrenner²⁴, Yang Li¹¹, Jacob Nattermann²⁵, Birgit Sawitzki², Antoine-Emmanuel Saliba⁶, Leif Erik Sander¹², Deutsche COVID-19 OMICS Initiative (DeCOI)

1. Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
2. Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
3. Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH) Berlin, Germany.
4. Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany.
5. Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
6. Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.
7. Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
8. German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
9. Mass Cytometry Lab, DRFZ Berlin, a Leibniz Institute, Berlin, Germany.
10. Flow and Mass Cytometry Core Facility, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
11. Centre for Individualised Infection Medicine (CiiM) and TWINCORE, joint ventures between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH), Hannover, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
12. Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL).
13. Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH) Berlin, Germany; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany.
14. Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
15. Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
16. Clinical Study Center (CSC), Charité, Universitätsmedizin Berlin, and Berlin Institute of Health, Berlin, Germany.
17. Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité, Universitätsmedizin Berlin, Berlin, Germany.
18. Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany.
19. Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany.
20. Genome Analytics, Helmholtz-Center for Infection Research (HZI), Braunschweig, Germany.
21. Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Infection Research (DZIF).
22. Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; Department of Tropical Medicine, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany; I. Department of Medicine, University Medical Center, Hamburg-Eppendorf, Hamburg, Germany.
23. Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany; German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany. Electronic address: j.schultze@uni-bonn.de.
24. Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany; Department of Internal Medicine and Radboud Center for Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
25. Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF).

Abstract

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.

Presented By Jonas Schulte-Schrepping | ORCID iD