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

Jonas Schulte-Schrepping; Nico Reusch; Daniela Paclik; Kevin Baßler; Stephan Schlickeiser; Bowen Zhang; Benjamin Krämer; Tobias Krammer; Sophia Brumhard; Lorenzo Bonaguro; Elena De Domenico; Daniel Wendisch; Martin Grasshoff; Theodore S. Kapellos; Michael Beckstette; Tal Pecht; Adem Saglam; Oliver Dietrich; Henrik E. Mei; Axel R. 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; Katrin Moira Heim; Felix Machleidt; Alexander Uhrig; Laure Bosquillon de Jarcy; Linda Jürgens; Miriam Stegemann; Christoph R. Glösenkamp; Hans Dieter Volk; Christine Goffinet; Markus Landthaler; Emanuel Wyler; Philipp Georg; Maria Schneider; Chantip Dang-Heine; Nick Neuwinger; Kai Kappert; Rudolf Tauber; Victor Corman

doi:10.1016/j.cell.2020.08.001

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

Jonas Schulte-Schrepping, Nico Reusch, Daniela Paclik, Kevin Baßler, Stephan Schlickeiser, Bowen Zhang, Benjamin Krämer, Tobias Krammer, Sophia Brumhard, Lorenzo Bonaguro, Elena De Domenico, Daniel Wendisch, Martin Grasshoff, Theodore S. Kapellos, Michael Beckstette, Tal Pecht, Adem Saglam, Oliver Dietrich, Henrik E. Mei, Axel R. SchulzClaudia 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, Katrin Moira Heim, Felix Machleidt, Alexander Uhrig, Laure Bosquillon de Jarcy, Linda Jürgens, Miriam Stegemann, Christoph R. Glösenkamp, Hans Dieter Volk, Christine Goffinet, Markus Landthaler, Emanuel Wyler, Philipp Georg, Maria Schneider, Chantip Dang-Heine, Nick Neuwinger, Kai Kappert, Rudolf Tauber, Victor Corman

Research output: Contribution to journal › Article › peer-review

1081 Citations (Scopus)

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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.

Original language	English
Pages (from-to)	1419-1440.e23
Journal	Cell
Volume	182
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2020.08.001
Publication status	Published - 17 Sept 2020
Externally published	Yes

Keywords

COVID-19
dysfunctional neutrophils
emergency myelopoiesis
immune profiling
mass cytometry
monocytes
neutrophils
SARS-CoV-2
scRNA-seq

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10.1016/j.cell.2020.08.001

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Schulte-Schrepping, J., Reusch, N., Paclik, D., Baßler, K., Schlickeiser, S., Zhang, B., Krämer, B., Krammer, T., Brumhard, S., Bonaguro, L., De Domenico, E., Wendisch, D., Grasshoff, M., Kapellos, T. S., Beckstette, M., Pecht, T., Saglam, A., Dietrich, O., Mei, H. E., ... Corman, V. (2020). Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment. Cell, 182(6), 1419-1440.e23. https://doi.org/10.1016/j.cell.2020.08.001

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title = "Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment",

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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.",

keywords = "COVID-19, dysfunctional neutrophils, emergency myelopoiesis, immune profiling, mass cytometry, monocytes, neutrophils, SARS-CoV-2, scRNA-seq",

author = "Jonas Schulte-Schrepping and Nico Reusch and Daniela Paclik and Kevin Ba{\ss}ler and Stephan Schlickeiser and Bowen Zhang and Benjamin Kr{\"a}mer and Tobias Krammer and Sophia Brumhard and Lorenzo Bonaguro and \{De Domenico\}, Elena and Daniel Wendisch and Martin Grasshoff and Kapellos, \{Theodore S.\} and Michael Beckstette and Tal Pecht and Adem Saglam and Oliver Dietrich and Mei, \{Henrik E.\} and Schulz, \{Axel R.\} and Claudia Conrad and D{\'e}sir{\'e}e Kunkel and Ehsan Vafadarnejad and Xu, \{Cheng Jian\} and Arik Horne and Miriam Herbert and Anna Drews and Charlotte Thibeault and Moritz Pfeiffer and Stefan Hippenstiel and Andreas Hocke and Holger M{\"u}ller-Redetzky and Heim, \{Katrin Moira\} and Felix Machleidt and Alexander Uhrig and \{Bosquillon de Jarcy\}, Laure and Linda J{\"u}rgens and Miriam Stegemann and Gl{\"o}senkamp, \{Christoph R.\} and Volk, \{Hans Dieter\} and Christine Goffinet and Markus Landthaler and Emanuel Wyler and Philipp Georg and Maria Schneider and Chantip Dang-Heine and Nick Neuwinger and Kai Kappert and Rudolf Tauber and Victor Corman",

year = "2020",

month = sep,

day = "17",

doi = "10.1016/j.cell.2020.08.001",

language = "English",

volume = "182",

pages = "1419--1440.e23",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "6",

}

Schulte-Schrepping, J, Reusch, N, Paclik, D, Baßler, K, Schlickeiser, S, Zhang, B, Krämer, B, Krammer, T, Brumhard, S, Bonaguro, L, De Domenico, E, Wendisch, D, Grasshoff, M, Kapellos, TS, Beckstette, M, Pecht, T, Saglam, A, Dietrich, O, Mei, HE, Schulz, AR, Conrad, C, Kunkel, D, Vafadarnejad, E, Xu, CJ, Horne, A, Herbert, M, Drews, A, Thibeault, C, Pfeiffer, M, Hippenstiel, S, Hocke, A, Müller-Redetzky, H, Heim, KM, Machleidt, F, Uhrig, A, Bosquillon de Jarcy, L, Jürgens, L, Stegemann, M, Glösenkamp, CR, Volk, HD, Goffinet, C, Landthaler, M, Wyler, E, Georg, P, Schneider, M, Dang-Heine, C, Neuwinger, N, Kappert, K, Tauber, R & Corman, V 2020, 'Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment', Cell, vol. 182, no. 6, pp. 1419-1440.e23. https://doi.org/10.1016/j.cell.2020.08.001

TY - JOUR

T1 - Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment

AU - Schulte-Schrepping, Jonas

AU - Reusch, Nico

AU - Paclik, Daniela

AU - Baßler, Kevin

AU - Schlickeiser, Stephan

AU - Zhang, Bowen

AU - Krämer, Benjamin

AU - Krammer, Tobias

AU - Brumhard, Sophia

AU - Bonaguro, Lorenzo

AU - De Domenico, Elena

AU - Wendisch, Daniel

AU - Grasshoff, Martin

AU - Kapellos, Theodore S.

AU - Beckstette, Michael

AU - Pecht, Tal

AU - Saglam, Adem

AU - Dietrich, Oliver

AU - Mei, Henrik E.

AU - Schulz, Axel R.

AU - Conrad, Claudia

AU - Kunkel, Désirée

AU - Vafadarnejad, Ehsan

AU - Xu, Cheng Jian

AU - Horne, Arik

AU - Herbert, Miriam

AU - Drews, Anna

AU - Thibeault, Charlotte

AU - Pfeiffer, Moritz

AU - Hippenstiel, Stefan

AU - Hocke, Andreas

AU - Müller-Redetzky, Holger

AU - Heim, Katrin Moira

AU - Machleidt, Felix

AU - Uhrig, Alexander

AU - Bosquillon de Jarcy, Laure

AU - Jürgens, Linda

AU - Stegemann, Miriam

AU - Glösenkamp, Christoph R.

AU - Volk, Hans Dieter

AU - Goffinet, Christine

AU - Landthaler, Markus

AU - Wyler, Emanuel

AU - Georg, Philipp

AU - Schneider, Maria

AU - Dang-Heine, Chantip

AU - Neuwinger, Nick

AU - Kappert, Kai

AU - Tauber, Rudolf

AU - Corman, Victor

PY - 2020/9/17

Y1 - 2020/9/17

N2 - 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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.

AB - 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. Analysis of patients with mild and severe COVID-19 reveals the presence of dysfunctional neutrophils in the latter that is linked to emergency myelopoiesis.

KW - COVID-19

KW - dysfunctional neutrophils

KW - emergency myelopoiesis

KW - immune profiling

KW - mass cytometry

KW - monocytes

KW - neutrophils

KW - SARS-CoV-2

KW - scRNA-seq

U2 - 10.1016/j.cell.2020.08.001

DO - 10.1016/j.cell.2020.08.001

M3 - Article

SN - 0092-8674

VL - 182

SP - 1419-1440.e23

JO - Cell

JF - Cell

IS - 6

ER -

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

Abstract

Keywords

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