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

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 cou...

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Autores principales: Schulte-Schrepping, Jonas, Reusch, Nico, Paclik, Daniela, Baßler, Kevin, Schlickeiser, Stephan, Zhang, Bowen, Krämer, Benjamin, Krammer, Tobias, Brumhard, Sophia, Bonaguro, Lorenzo, De Domenico, Elena, Wendisch, Daniel, Grasshoff, Martin, Kapellos, Theodore S., Beckstette, Michael, Pecht, Tal, Saglam, Adem, Dietrich, Oliver, Mei, Henrik E., Schulz, Axel R., Conrad, Claudia, Kunkel, Désirée, Vafadarnejad, Ehsan, Xu, Cheng-Jian, Horne, Arik, Herbert, Miriam, Drews, Anna, Thibeault, Charlotte, Pfeiffer, Moritz, Hippenstiel, Stefan, Hocke, Andreas, Müller-Redetzky, Holger, Heim, Katrin-Moira, Machleidt, Felix, Uhrig, Alexander, Bosquillon de Jarcy, Laure, Jürgens, Linda, Stegemann, Miriam, Glösenkamp, Christoph R., Volk, Hans-Dieter, Goffinet, Christine, Landthaler, Markus, Wyler, Emanuel, Georg, Philipp, Schneider, Maria, Dang-Heine, Chantip, Neuwinger, Nick, Kappert, Kai, Tauber, Rudolf, Corman, Victor, Raabe, Jan, Kaiser, Kim Melanie, Vinh, Michael To, Rieke, Gereon, Meisel, Christian, Ulas, Thomas, Becker, Matthias, Geffers, Robert, Witzenrath, Martin, Drosten, Christian, Suttorp, Norbert, von Kalle, Christof, Kurth, Florian, Händler, Kristian, Schultze, Joachim L., Aschenbrenner, Anna C., Li, Yang, Nattermann, Jacob, Sawitzki, Birgit, Saliba, Antoine-Emmanuel, Sander, Leif Erik
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405822/
https://www.ncbi.nlm.nih.gov/pubmed/32810438
http://dx.doi.org/10.1016/j.cell.2020.08.001
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author Schulte-Schrepping, Jonas
Reusch, Nico
Paclik, Daniela
Baßler, Kevin
Schlickeiser, Stephan
Zhang, Bowen
Krämer, Benjamin
Krammer, Tobias
Brumhard, Sophia
Bonaguro, Lorenzo
De Domenico, Elena
Wendisch, Daniel
Grasshoff, Martin
Kapellos, Theodore S.
Beckstette, Michael
Pecht, Tal
Saglam, Adem
Dietrich, Oliver
Mei, Henrik E.
Schulz, Axel R.
Conrad, Claudia
Kunkel, Désirée
Vafadarnejad, Ehsan
Xu, Cheng-Jian
Horne, Arik
Herbert, Miriam
Drews, Anna
Thibeault, Charlotte
Pfeiffer, Moritz
Hippenstiel, Stefan
Hocke, Andreas
Müller-Redetzky, Holger
Heim, Katrin-Moira
Machleidt, Felix
Uhrig, Alexander
Bosquillon de Jarcy, Laure
Jürgens, Linda
Stegemann, Miriam
Glösenkamp, Christoph R.
Volk, Hans-Dieter
Goffinet, Christine
Landthaler, Markus
Wyler, Emanuel
Georg, Philipp
Schneider, Maria
Dang-Heine, Chantip
Neuwinger, Nick
Kappert, Kai
Tauber, Rudolf
Corman, Victor
Raabe, Jan
Kaiser, Kim Melanie
Vinh, Michael To
Rieke, Gereon
Meisel, Christian
Ulas, Thomas
Becker, Matthias
Geffers, Robert
Witzenrath, Martin
Drosten, Christian
Suttorp, Norbert
von Kalle, Christof
Kurth, Florian
Händler, Kristian
Schultze, Joachim L.
Aschenbrenner, Anna C.
Li, Yang
Nattermann, Jacob
Sawitzki, Birgit
Saliba, Antoine-Emmanuel
Sander, Leif Erik
author_facet Schulte-Schrepping, Jonas
Reusch, Nico
Paclik, Daniela
Baßler, Kevin
Schlickeiser, Stephan
Zhang, Bowen
Krämer, Benjamin
Krammer, Tobias
Brumhard, Sophia
Bonaguro, Lorenzo
De Domenico, Elena
Wendisch, Daniel
Grasshoff, Martin
Kapellos, Theodore S.
Beckstette, Michael
Pecht, Tal
Saglam, Adem
Dietrich, Oliver
Mei, Henrik E.
Schulz, Axel R.
Conrad, Claudia
Kunkel, Désirée
Vafadarnejad, Ehsan
Xu, Cheng-Jian
Horne, Arik
Herbert, Miriam
Drews, Anna
Thibeault, Charlotte
Pfeiffer, Moritz
Hippenstiel, Stefan
Hocke, Andreas
Müller-Redetzky, Holger
Heim, Katrin-Moira
Machleidt, Felix
Uhrig, Alexander
Bosquillon de Jarcy, Laure
Jürgens, Linda
Stegemann, Miriam
Glösenkamp, Christoph R.
Volk, Hans-Dieter
Goffinet, Christine
Landthaler, Markus
Wyler, Emanuel
Georg, Philipp
Schneider, Maria
Dang-Heine, Chantip
Neuwinger, Nick
Kappert, Kai
Tauber, Rudolf
Corman, Victor
Raabe, Jan
Kaiser, Kim Melanie
Vinh, Michael To
Rieke, Gereon
Meisel, Christian
Ulas, Thomas
Becker, Matthias
Geffers, Robert
Witzenrath, Martin
Drosten, Christian
Suttorp, Norbert
von Kalle, Christof
Kurth, Florian
Händler, Kristian
Schultze, Joachim L.
Aschenbrenner, Anna C.
Li, Yang
Nattermann, Jacob
Sawitzki, Birgit
Saliba, Antoine-Emmanuel
Sander, Leif Erik
author_sort Schulte-Schrepping, Jonas
collection PubMed
description 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-DR(hi)CD11c(hi) 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-DR(lo) 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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spelling pubmed-74058222020-08-05 Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment Schulte-Schrepping, Jonas Reusch, Nico Paclik, Daniela Baßler, Kevin Schlickeiser, Stephan Zhang, Bowen Krämer, Benjamin Krammer, Tobias Brumhard, Sophia Bonaguro, Lorenzo De Domenico, Elena Wendisch, Daniel Grasshoff, Martin Kapellos, Theodore S. Beckstette, Michael Pecht, Tal Saglam, Adem Dietrich, Oliver Mei, Henrik E. Schulz, Axel R. Conrad, Claudia Kunkel, Désirée Vafadarnejad, Ehsan Xu, Cheng-Jian Horne, Arik Herbert, Miriam Drews, Anna Thibeault, Charlotte Pfeiffer, Moritz Hippenstiel, Stefan Hocke, Andreas Müller-Redetzky, Holger Heim, Katrin-Moira Machleidt, Felix Uhrig, Alexander Bosquillon de Jarcy, Laure Jürgens, Linda Stegemann, Miriam Glösenkamp, Christoph R. Volk, Hans-Dieter Goffinet, Christine Landthaler, Markus Wyler, Emanuel Georg, Philipp Schneider, Maria Dang-Heine, Chantip Neuwinger, Nick Kappert, Kai Tauber, Rudolf Corman, Victor Raabe, Jan Kaiser, Kim Melanie Vinh, Michael To Rieke, Gereon Meisel, Christian Ulas, Thomas Becker, Matthias Geffers, Robert Witzenrath, Martin Drosten, Christian Suttorp, Norbert von Kalle, Christof Kurth, Florian Händler, Kristian Schultze, Joachim L. Aschenbrenner, Anna C. Li, Yang Nattermann, Jacob Sawitzki, Birgit Saliba, Antoine-Emmanuel Sander, Leif Erik Cell Article 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-DR(hi)CD11c(hi) 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-DR(lo) 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. Elsevier Inc. 2020-09-17 2020-08-05 /pmc/articles/PMC7405822/ /pubmed/32810438 http://dx.doi.org/10.1016/j.cell.2020.08.001 Text en © 2020 Elsevier Inc. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Article
Schulte-Schrepping, Jonas
Reusch, Nico
Paclik, Daniela
Baßler, Kevin
Schlickeiser, Stephan
Zhang, Bowen
Krämer, Benjamin
Krammer, Tobias
Brumhard, Sophia
Bonaguro, Lorenzo
De Domenico, Elena
Wendisch, Daniel
Grasshoff, Martin
Kapellos, Theodore S.
Beckstette, Michael
Pecht, Tal
Saglam, Adem
Dietrich, Oliver
Mei, Henrik E.
Schulz, Axel R.
Conrad, Claudia
Kunkel, Désirée
Vafadarnejad, Ehsan
Xu, Cheng-Jian
Horne, Arik
Herbert, Miriam
Drews, Anna
Thibeault, Charlotte
Pfeiffer, Moritz
Hippenstiel, Stefan
Hocke, Andreas
Müller-Redetzky, Holger
Heim, Katrin-Moira
Machleidt, Felix
Uhrig, Alexander
Bosquillon de Jarcy, Laure
Jürgens, Linda
Stegemann, Miriam
Glösenkamp, Christoph R.
Volk, Hans-Dieter
Goffinet, Christine
Landthaler, Markus
Wyler, Emanuel
Georg, Philipp
Schneider, Maria
Dang-Heine, Chantip
Neuwinger, Nick
Kappert, Kai
Tauber, Rudolf
Corman, Victor
Raabe, Jan
Kaiser, Kim Melanie
Vinh, Michael To
Rieke, Gereon
Meisel, Christian
Ulas, Thomas
Becker, Matthias
Geffers, Robert
Witzenrath, Martin
Drosten, Christian
Suttorp, Norbert
von Kalle, Christof
Kurth, Florian
Händler, Kristian
Schultze, Joachim L.
Aschenbrenner, Anna C.
Li, Yang
Nattermann, Jacob
Sawitzki, Birgit
Saliba, Antoine-Emmanuel
Sander, Leif Erik
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title_full Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title_fullStr Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title_full_unstemmed Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title_short Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
title_sort severe covid-19 is marked by a dysregulated myeloid cell compartment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405822/
https://www.ncbi.nlm.nih.gov/pubmed/32810438
http://dx.doi.org/10.1016/j.cell.2020.08.001
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