tetano
Editor, Senior Moderator
Cell
. 2020 Aug 5;S0092-8674(20)30992-2.
doi: 10.1016/j.cell.2020.08.001. Online ahead of print.
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
Jonas Schulte-Schrepping[SUP] 1 [/SUP], Nico Reusch[SUP] 1 [/SUP], Daniela Paclik[SUP] 2 [/SUP], Kevin Ba?ler[SUP] 1 [/SUP], Stephan Schlickeiser[SUP] 3 [/SUP], Bowen Zhang[SUP] 4 [/SUP], Benjamin Kr?mer[SUP] 5 [/SUP], Tobias Krammer[SUP] 6 [/SUP], Sophia Brumhard[SUP] 7 [/SUP], Lorenzo Bonaguro[SUP] 1 [/SUP], Elena De Domenico[SUP] 8 [/SUP], Daniel Wendisch[SUP] 7 [/SUP], Martin Grasshoff[SUP] 4 [/SUP], Theodore S Kapellos[SUP] 1 [/SUP], Michael Beckstette[SUP] 4 [/SUP], Tal Pecht[SUP] 1 [/SUP], Adem Saglam[SUP] 8 [/SUP], Oliver Dietrich[SUP] 6 [/SUP], Henrik E Mei[SUP] 9 [/SUP], Axel R Schulz[SUP] 9 [/SUP], Claudia Conrad[SUP] 7 [/SUP], D?sir?e Kunkel[SUP] 10 [/SUP], Ehsan Vafadarnejad[SUP] 6 [/SUP], Cheng-Jian Xu[SUP] 11 [/SUP], Arik Horne[SUP] 1 [/SUP], Miriam Herbert[SUP] 1 [/SUP], Anna Drews[SUP] 8 [/SUP], Charlotte Thibeault[SUP] 7 [/SUP], Moritz Pfeiffer[SUP] 7 [/SUP], Stefan Hippenstiel[SUP] 12 [/SUP], Andreas Hocke[SUP] 12 [/SUP], Holger M?ller-Redetzky[SUP] 7 [/SUP], Katrin-Moira Heim[SUP] 7 [/SUP], Felix Machleidt[SUP] 7 [/SUP], Alexander Uhrig[SUP] 7 [/SUP], Laure Bosquillon de Jarcy[SUP] 7 [/SUP], Linda J?rgens[SUP] 7 [/SUP], Miriam Stegemann[SUP] 7 [/SUP], Christoph R Gl?senkamp[SUP] 7 [/SUP], Hans-Dieter Volk[SUP] 13 [/SUP], Christine Goffinet[SUP] 14 [/SUP], Markus Landthaler[SUP] 15 [/SUP], Emanuel Wyler[SUP] 15 [/SUP], Philipp Georg[SUP] 7 [/SUP], Maria Schneider[SUP] 2 [/SUP], Chantip Dang-Heine[SUP] 16 [/SUP], Nick Neuwinger[SUP] 17 [/SUP], Kai Kappert[SUP] 17 [/SUP], Rudolf Tauber[SUP] 17 [/SUP], Victor Corman[SUP] 18 [/SUP], Jan Raabe[SUP] 5 [/SUP], Kim Melanie Kaiser[SUP] 5 [/SUP], Michael To Vinh[SUP] 5 [/SUP], Gereon Rieke[SUP] 5 [/SUP], Christian Meisel[SUP] 19 [/SUP], Thomas Ulas[SUP] 8 [/SUP], Matthias Becker[SUP] 8 [/SUP], Robert Geffers[SUP] 20 [/SUP], Martin Witzenrath[SUP] 12 [/SUP], Christian Drosten[SUP] 21 [/SUP], Norbert Suttorp[SUP] 12 [/SUP], Christof von Kalle[SUP] 16 [/SUP], Florian Kurth[SUP] 22 [/SUP], Kristian H?ndler[SUP] 8 [/SUP], Joachim L Schultze[SUP] 23 [/SUP], Anna C Aschenbrenner[SUP] 24 [/SUP], Yang Li[SUP] 11 [/SUP], Jacob Nattermann[SUP] 25 [/SUP], Birgit Sawitzki[SUP] 2 [/SUP], Antoine-Emmanuel Saliba[SUP] 6 [/SUP], Leif Erik Sander[SUP] 12 [/SUP], Deutsche COVID-19 OMICS Initiative (DeCOI)
Collaborators, Affiliations
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-DR[SUP]hi[/SUP]CD11c[SUP]hi[/SUP] 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[SUP]lo[/SUP] 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.
Keywords: COVID-19; SARS-CoV-2; dysfunctional neutrophils; emergency myelopoiesis; immune profiling; mass cytometry; monocytes; neutrophils; scRNA-seq.
. 2020 Aug 5;S0092-8674(20)30992-2.
doi: 10.1016/j.cell.2020.08.001. Online ahead of print.
Severe COVID-19 Is Marked by a Dysregulated Myeloid Cell Compartment
Jonas Schulte-Schrepping[SUP] 1 [/SUP], Nico Reusch[SUP] 1 [/SUP], Daniela Paclik[SUP] 2 [/SUP], Kevin Ba?ler[SUP] 1 [/SUP], Stephan Schlickeiser[SUP] 3 [/SUP], Bowen Zhang[SUP] 4 [/SUP], Benjamin Kr?mer[SUP] 5 [/SUP], Tobias Krammer[SUP] 6 [/SUP], Sophia Brumhard[SUP] 7 [/SUP], Lorenzo Bonaguro[SUP] 1 [/SUP], Elena De Domenico[SUP] 8 [/SUP], Daniel Wendisch[SUP] 7 [/SUP], Martin Grasshoff[SUP] 4 [/SUP], Theodore S Kapellos[SUP] 1 [/SUP], Michael Beckstette[SUP] 4 [/SUP], Tal Pecht[SUP] 1 [/SUP], Adem Saglam[SUP] 8 [/SUP], Oliver Dietrich[SUP] 6 [/SUP], Henrik E Mei[SUP] 9 [/SUP], Axel R Schulz[SUP] 9 [/SUP], Claudia Conrad[SUP] 7 [/SUP], D?sir?e Kunkel[SUP] 10 [/SUP], Ehsan Vafadarnejad[SUP] 6 [/SUP], Cheng-Jian Xu[SUP] 11 [/SUP], Arik Horne[SUP] 1 [/SUP], Miriam Herbert[SUP] 1 [/SUP], Anna Drews[SUP] 8 [/SUP], Charlotte Thibeault[SUP] 7 [/SUP], Moritz Pfeiffer[SUP] 7 [/SUP], Stefan Hippenstiel[SUP] 12 [/SUP], Andreas Hocke[SUP] 12 [/SUP], Holger M?ller-Redetzky[SUP] 7 [/SUP], Katrin-Moira Heim[SUP] 7 [/SUP], Felix Machleidt[SUP] 7 [/SUP], Alexander Uhrig[SUP] 7 [/SUP], Laure Bosquillon de Jarcy[SUP] 7 [/SUP], Linda J?rgens[SUP] 7 [/SUP], Miriam Stegemann[SUP] 7 [/SUP], Christoph R Gl?senkamp[SUP] 7 [/SUP], Hans-Dieter Volk[SUP] 13 [/SUP], Christine Goffinet[SUP] 14 [/SUP], Markus Landthaler[SUP] 15 [/SUP], Emanuel Wyler[SUP] 15 [/SUP], Philipp Georg[SUP] 7 [/SUP], Maria Schneider[SUP] 2 [/SUP], Chantip Dang-Heine[SUP] 16 [/SUP], Nick Neuwinger[SUP] 17 [/SUP], Kai Kappert[SUP] 17 [/SUP], Rudolf Tauber[SUP] 17 [/SUP], Victor Corman[SUP] 18 [/SUP], Jan Raabe[SUP] 5 [/SUP], Kim Melanie Kaiser[SUP] 5 [/SUP], Michael To Vinh[SUP] 5 [/SUP], Gereon Rieke[SUP] 5 [/SUP], Christian Meisel[SUP] 19 [/SUP], Thomas Ulas[SUP] 8 [/SUP], Matthias Becker[SUP] 8 [/SUP], Robert Geffers[SUP] 20 [/SUP], Martin Witzenrath[SUP] 12 [/SUP], Christian Drosten[SUP] 21 [/SUP], Norbert Suttorp[SUP] 12 [/SUP], Christof von Kalle[SUP] 16 [/SUP], Florian Kurth[SUP] 22 [/SUP], Kristian H?ndler[SUP] 8 [/SUP], Joachim L Schultze[SUP] 23 [/SUP], Anna C Aschenbrenner[SUP] 24 [/SUP], Yang Li[SUP] 11 [/SUP], Jacob Nattermann[SUP] 25 [/SUP], Birgit Sawitzki[SUP] 2 [/SUP], Antoine-Emmanuel Saliba[SUP] 6 [/SUP], Leif Erik Sander[SUP] 12 [/SUP], Deutsche COVID-19 OMICS Initiative (DeCOI)
Collaborators, Affiliations
- PMID: 32810438
- DOI: 10.1016/j.cell.2020.08.001
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-DR[SUP]hi[/SUP]CD11c[SUP]hi[/SUP] 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[SUP]lo[/SUP] 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.
Keywords: COVID-19; SARS-CoV-2; dysfunctional neutrophils; emergency myelopoiesis; immune profiling; mass cytometry; monocytes; neutrophils; scRNA-seq.