Suppressive myeloid cells are a hallmark of severe COVID-19 Article Swipe

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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 Schulz , Claudia Conrad , Désirée Kunkel , Ehsan Vafadarnejad , Cheng‐Jian Xu , Arik Horne , Miriam Herbert , Anna Drews , Charlotte Thibeault , Moritz Pfeiffer , Stefan Hippenstiel , Andreas C. Hocke , Holger Müller-Redetzky , Kathrin Heim , Felix Machleidt , Alexander Uhrig , Laure Bousquillon de Jarcy , Linda Jürgens , Miriam Stegemann , Christoph R. Glösenkamp , Hans‐Dieter Volk , Christine Goffinet , Jan Raabe , Kim M Kaiser , M To Vinh , Gereon Rieke , Christian Meisel , Thomas Ulas , Matthias Becker , Robert Geffers , Martin Witzenrath , Christian Drosten , Norbert Suttorp , Christof von Kalle , Florian Kurth , Kristian Händler , Joachim L. Schultze , Anna C. Aschenbrenner , Yang Li , Jacob Nattermann , Birgit Sawitzki , Antoine‐Emmanuel Saliba , Leif Erik Sander ·

YOU? · · 2020 · Open Access · · DOI: https://doi.org/10.1101/2020.06.03.20119818

‘Severe Acute Respiratory Syndrome - Coronavirus-2’ (SARS-CoV-2) infection causes Coronavirus Disease 2019 (COVID-19), a mild to moderate respiratory tract infection in the majority of patients. A subset of patients, however, progresses to severe disease and respiratory failure with acute respiratory distress syndrome (ARDS). Severe COVID-19 has been associated with increased neutrophil counts and dysregulated immune responses. The mechanisms of protective immunity in mild forms and the pathogenesis of dysregulated inflammation in severe courses of COVID-19 remain largely unclear. Here, we combined two single-cell RNA-sequencing technologies and single-cell proteomics in whole blood and peripheral blood mononuclear cells (PBMC) to determine changes in immune cell composition and activation in two independent dual-center patient cohorts (n=46+n=54 COVID-19 samples), each with mild and severe cases of COVID-19. We observed a specific increase of HLA-DR hi CD11c hi inflammatory monocytes that displayed a strong interferon (IFN)-stimulated gene signature in patients with mild COVID-19, which was absent in severe disease. Instead, we found evidence of emergency myelopoiesis, marked by the occurrence of immunosuppressive pre-neutrophils and immature neutrophils and populations of dysfunctional and suppressive mature neutrophils, as well as suppressive HLA-DR to monocytes in severe COVID-19. Our study provides detailed insights into systemic immune response to SARS-CoV-2 infection and it reveals profound alterations in the peripheral myeloid cell compartment associated with severe courses of COVID-19.

Related Topics

Immunology

Acute Respiratory Distress Syndrome

Concepts

Immunology ARDS Immune system Peripheral blood mononuclear cell Medicine Myeloid Inflammation Pathogenesis Biology Lung Internal medicine Biochemistry In vitro

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2020.06.03.20119818
PDF: https://www.medrxiv.org/content/medrxiv/early/2020/06/05/2020.06.03.20119818.full.pdf
OA Status: green
Cited By: 35
References: 107
Related Works: 10
OpenAlex ID: https://openalex.org/W3033606359

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OpenAlex ID: https://openalex.org/W3033606359

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DOI: https://doi.org/10.1101/2020.06.03.20119818

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Title: Suppressive myeloid cells are a hallmark of severe COVID-19

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Type: preprint

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Language: en

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Publication year: 2020

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Publication date: 2020-06-05

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Authors: 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 Schulz, Claudia Conrad, Désirée Kunkel, Ehsan Vafadarnejad, Cheng‐Jian Xu, Arik Horne, Miriam Herbert, Anna Drews, Charlotte Thibeault, Moritz Pfeiffer, Stefan Hippenstiel, Andreas C. Hocke, Holger Müller-Redetzky, Kathrin Heim, Felix Machleidt, Alexander Uhrig, Laure Bousquillon de Jarcy, Linda Jürgens, Miriam Stegemann, Christoph R. Glösenkamp, Hans‐Dieter Volk, Christine Goffinet, Jan Raabe, Kim M Kaiser, M To Vinh, Gereon Rieke, Christian Meisel, Thomas Ulas, Matthias Becker, Robert Geffers, Martin Witzenrath, Christian Drosten, Norbert Suttorp, Christof von Kalle, Florian Kurth, Kristian Händler, Joachim L. Schultze, Anna C. Aschenbrenner, Yang Li, Jacob Nattermann, Birgit Sawitzki, Antoine‐Emmanuel Saliba, Leif Erik Sander

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Landing page: https://doi.org/10.1101/2020.06.03.20119818

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PDF URL: https://www.medrxiv.org/content/medrxiv/early/2020/06/05/2020.06.03.20119818.full.pdf

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OA URL: https://www.medrxiv.org/content/medrxiv/early/2020/06/05/2020.06.03.20119818.full.pdf

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Concepts: Immunology, ARDS, Immune system, Peripheral blood mononuclear cell, Medicine, Myeloid, Inflammation, Pathogenesis, Biology, Lung, Internal medicine, Biochemistry, In vitro

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Cited by: 35

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