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

Authors
Jonas Schulte-Schrepping,Nico Reusch
Daniela Paclik,Kevin Baßler,Stephan Schlickeiser,Bowen Zhang,Benjamin Krämer,Tobias Krammer,Sophia Brumhard,Lorenzo Bonaguro,Elena Domenico,Daniel Wendisch,Martin Grasshoff,Theodore Kapellos,Michael Beckstette,Tal Pecht,Adem Saglam,Oliver Dietrich,Henrik Mei,Axel Schulz,Claudia Conrad,Désirée Kunkel,Ehsan Vafadarnejad,Cheng‐Jian Xu,Arik Horne,Miriam Herbert,Anna Drews,Charlotte Thibeault,Moritz Pfeiffer,Stefan Hippenstiel,Andreas Hocke,Holger Müller-Redetzky,Kathrin Heim,Felix Machleidt,Alexander Uhrig,Laure Jarcy,Linda Jürgens,Miriam Stegemann,Christoph Glösenkamp,Hans‐Dieter Volk,Christine Goffinet,Markus Landthaler,Emanuel Wyler,Philipp Georg,Maria Schneider,Chantip Dang‐Heine,Nick Neuwinger,Kai Kappert,R Tauber,Victor Corman,Jan Raabe,Kim Kaiser,M Vinh,Gereon Rieke,Christian Meisel,Thomas Ulas,Matthias Becker,Robert Geffers,Martin Witzenrath,Christian Drosten,Norbert Suttorp,Christof Kalle,Florian Kurth,Kristian Händler,Joachim Schultze,Anna Aschenbrenner,Yang Li,Jacob Nattermann,Birgit Sawitzki,Antoine‐Emmanuel Saliba,Leif Sander,Angel Angelov,Robert Bals,Alexander Bartholomäus,Anke Becker,Daniela Bezdan,Ezio Bonifacio,Peer Bork,Thomas Clavel,Maria Colomé-Tatché,Andreas Diefenbach,Alexander Dilthey,Nicole Fischer,Konrad Förstner,Julia-Stefanie Frick,Julien Gagneur,Alexander Goesmann,Torsten Hain,Michael Hummel,Stefan Janssen,Jörn Kalinowski,René Kallies,Birte Kehr,Andreas Keller,Sarah Kim-Hellmuth,Christoph Klein,Oliver Kohlbacher,Jan Korbel,Ingo Kurth,Kerstin Ludwig,Oliwia Makarewicz,Manja Marz,Alice McHardy,Christian Mertes,Markus Nöthen,Peter Nürnberg,Uwe Ohler,Stephan Ossowski,Jörg Overmann,Silke Peter,Klaus Pfeffer,Anna Poetsch,Alfred Pühler,Nikolaus Rajewsky,Markus Ralser,Olaf Rieß,Stephan Ripke,Ulisses Rocha,Philip Rosenstiel,Philipp Schiffer,Eva Schulte,Alexander Sczyrba,Oliver Stegle,Jens Stoye,Fabian Theis,Jörg Vehreschild,Jörg Vogel,Max Kleist,Jörn Walter,Dagmar Wieczorek,John Ziebuhr
+129 authors
,Charlotte Keller
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Aug 5, 2020
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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.

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