HCA Data Explorer

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

Updated March 16, 2023

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.

Joachim L SchultzeLife 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.j.schultze@uni-bonn.de
Bruce AronowCincinnati Children's Hospital Medical Center (CCHMC)bruce.aronow@cchmc.org
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 Schultze (Experimental Scientist)23
Anna C Aschenbrenner24
Yang Li11
Jacob Nattermann25
Birgit Sawitzki2
Antoine-Emmanuel Saliba6
Leif Erik Sander12
Bruce Aronow26
1Life and Medical Sciences (LIMES) Institute, University of Bonn, Germany.
2Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.
3Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; BIH Center for Regenerative Therapies, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH) Berlin, Germany.
4Centre 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.
5Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany.
6Helmholtz Institute for RNA-based Infection Research (HIRI), Helmholtz-Center for Infection Research (HZI), Würzburg, Germany.
7Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany.
8German Center for Neurodegenerative Diseases (DZNE), PRECISE Platform for Genomics and Epigenomics at DZNE, and University of Bonn, Bonn, Germany.
9Mass Cytometry Lab, DRFZ Berlin, a Leibniz Institute, Berlin, Germany.
10Flow and Mass Cytometry Core Facility, Charité, Universitätsmedizin Berlin, and Berlin Institute of Health (BIH), Berlin, Germany.
11Centre 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.
12Department of Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Berlin, Germany; German Center for Lung Research (DZL).
13Institute 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.
14Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
15Berlin Institute for Medical Systems Biology, Max-Delbrück-Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany.
16Clinical Study Center (CSC), Charité, Universitätsmedizin Berlin, and Berlin Institute of Health, Berlin, Germany.
17Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany; Institute of Laboratory Medicine, Clinical Chemistry, and Pathobiochemistry, Charité, Universitätsmedizin Berlin, Berlin, Germany.
18Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany.
19Institute of Medical Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany; Department of Immunology, Labor Berlin-Charité Vivantes, Berlin, Germany.
20Genome Analytics, Helmholtz-Center for Infection Research (HZI), Braunschweig, Germany.
21Institute of Virology, Charité Universitätsmedizin Berlin, Berlin, Germany; German Center for Infection Research (DZIF).
22Department 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.
23Life 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.
24Life 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.
25Department of Internal Medicine I, University Hospital Bonn, Bonn, Germany; German Center for Infection Research (DZIF).
26Cincinnati Children's Hospital Medical Center (CCHMC)
Rachel Schwartz

To reference this project, please use the following link:

https://explore.data.humancellatlas.org/projects/cd9d6360-ce38-4321-97df-f13c79e3cb84
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Analysis Portals

UCSC Cell BrowserUCSC Cell Browser

Project Label

SchulteSchrepping2020

Species

Homo sapiens

Sample Type

specimens

Anatomical Entity

blood

Organ Part

Unspecified

Selected Cell Types

peripheral blood mononuclear cell

Disease Status (Specimen)

2 disease statuses

Disease Status (Donor)

5 disease statuses

Development Stage

human adult stage

Library Construction Method

2 library construction methods

Nucleic Acid Source

single cell

Paired End

false

Analysis Protocol

analysis_protocol_1, analysis_protocol_2

File Format

2 file formats

Cell Count Estimate

91.0k

Donor Count

39
h5ad1 file(s)xlsx1 file(s)