tetano
Editor, Senior Moderator
J Thromb Haemost
. 2020 Nov 20.
doi: 10.1111/jth.15179. Online ahead of print.
Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia
Leo Nicolai[SUP] 1 2 3 [/SUP], Alexander Leunig[SUP] 1 2 [/SUP], Sophia Brambs[SUP] 1 [/SUP], Rainer Kaiser[SUP] 1 2 3 [/SUP], Markus Joppich[SUP] 4 [/SUP], Marie Hoffknecht[SUP] 1 [/SUP], Christoph Gold[SUP] 1 [/SUP], Anouk Engel[SUP] 1 [/SUP], Vivien Polewka[SUP] 1 [/SUP], Maximilian Muenchhoff[SUP] 3 5 6 [/SUP], Johannes C Hellmuth[SUP] 3 7 8 [/SUP], Adrian Ruhle[SUP] 3 5 [/SUP], Stephan Ledderose[SUP] 9 [/SUP], Tobias Weinberger[SUP] 1 2 3 [/SUP], Heiko Schulz[SUP] 9 [/SUP], Clemens Scherer[SUP] 1 2 3 [/SUP], Martina Rudelius[SUP] 9 [/SUP], Michael Zoller[SUP] 10 [/SUP], Oliver T Keppler[SUP] 3 5 6 [/SUP], Bernhard Zwi?ler[SUP] 10 [/SUP], Michael von Bergwelt-Baildon[SUP] 3 7 8 [/SUP], Stefan K??b[SUP] 1 2 3 [/SUP], Ralf Zimmer[SUP] 4 [/SUP], Roman D B?low[SUP] 11 [/SUP], Saskia von Stillfried[SUP] 11 [/SUP], Peter Boor[SUP] 11 12 [/SUP], Steffen Massberg[SUP] 1 2 3 [/SUP], Kami Pekayvaz[SUP] 1 2 3 [/SUP], Konstantin Stark[SUP] 1 2 3 [/SUP]
Affiliations
Abstract
Objective: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of Coronavirus Disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation.
Approach and results: By comparing histopathological specimens of SARS-CoV-2 with influenza affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID-19, but less prominent in influenza pneumonia. Activated neutrophils were typically found in physical association with monocytes. To explore this further, we combined clinical data of COVID-19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA-seq data. We show that a HLADR[SUP]low[/SUP] CD9[SUP]low[/SUP] monocyte population expands in severe COVID-19, which releases neutrophil chemokines in the lung, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID-19.
Conclusions: In summary, our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; immunopathology; immunothrombosis; monocytes; neutrophils.
. 2020 Nov 20.
doi: 10.1111/jth.15179. Online ahead of print.
Vascular neutrophilic inflammation and immunothrombosis distinguish severe COVID-19 from influenza pneumonia
Leo Nicolai[SUP] 1 2 3 [/SUP], Alexander Leunig[SUP] 1 2 [/SUP], Sophia Brambs[SUP] 1 [/SUP], Rainer Kaiser[SUP] 1 2 3 [/SUP], Markus Joppich[SUP] 4 [/SUP], Marie Hoffknecht[SUP] 1 [/SUP], Christoph Gold[SUP] 1 [/SUP], Anouk Engel[SUP] 1 [/SUP], Vivien Polewka[SUP] 1 [/SUP], Maximilian Muenchhoff[SUP] 3 5 6 [/SUP], Johannes C Hellmuth[SUP] 3 7 8 [/SUP], Adrian Ruhle[SUP] 3 5 [/SUP], Stephan Ledderose[SUP] 9 [/SUP], Tobias Weinberger[SUP] 1 2 3 [/SUP], Heiko Schulz[SUP] 9 [/SUP], Clemens Scherer[SUP] 1 2 3 [/SUP], Martina Rudelius[SUP] 9 [/SUP], Michael Zoller[SUP] 10 [/SUP], Oliver T Keppler[SUP] 3 5 6 [/SUP], Bernhard Zwi?ler[SUP] 10 [/SUP], Michael von Bergwelt-Baildon[SUP] 3 7 8 [/SUP], Stefan K??b[SUP] 1 2 3 [/SUP], Ralf Zimmer[SUP] 4 [/SUP], Roman D B?low[SUP] 11 [/SUP], Saskia von Stillfried[SUP] 11 [/SUP], Peter Boor[SUP] 11 12 [/SUP], Steffen Massberg[SUP] 1 2 3 [/SUP], Kami Pekayvaz[SUP] 1 2 3 [/SUP], Konstantin Stark[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 33217134
- DOI: 10.1111/jth.15179
Abstract
Objective: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to severe pneumonia, but also thrombotic complications and non-pulmonary organ failure. Recent studies suggest intravascular neutrophil activation and subsequent immune cell triggered immunothrombosis as a central pathomechanism linking the heterogenous clinical picture of Coronavirus Disease 2019 (COVID-19). We sought to study whether immunothrombosis is a pathognomonic factor in COVID-19 or a general feature of (viral) pneumonia, as well as to better understand its upstream regulation.
Approach and results: By comparing histopathological specimens of SARS-CoV-2 with influenza affected lungs, we show that vascular neutrophil recruitment, NETosis, and subsequent immunothrombosis are typical features of severe COVID-19, but less prominent in influenza pneumonia. Activated neutrophils were typically found in physical association with monocytes. To explore this further, we combined clinical data of COVID-19 cases with comprehensive immune cell phenotyping and bronchoalveolar lavage fluid scRNA-seq data. We show that a HLADR[SUP]low[/SUP] CD9[SUP]low[/SUP] monocyte population expands in severe COVID-19, which releases neutrophil chemokines in the lung, and might in turn explain neutrophil expansion and pulmonary recruitment in the late stages of severe COVID-19.
Conclusions: In summary, our data underline an innate immune cell axis causing vascular inflammation and immunothrombosis in severe SARS-CoV-2 infection.
Keywords: COVID-19; SARS-CoV-2; immunopathology; immunothrombosis; monocytes; neutrophils.