tetano
Editor, Senior Moderator
Wellcome Open Res
. 2021 Feb 22;6:38.
doi: 10.12688/wellcomeopenres.16584.1. eCollection 2021.
-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--
Leila Reyes[SUP] #[/SUP][SUP] 1 [/SUP], Manuel A Sanchez-Garcia[SUP] #[/SUP][SUP] 1 [/SUP], Tyler Morrison[SUP] #[/SUP][SUP] 1 [/SUP], Andy J M Howden[SUP] #[/SUP][SUP] 2 [/SUP], Emily R Watts[SUP] 1 [/SUP], Simone Arienti[SUP] 1 [/SUP], Pranvera Sadiku[SUP] 1 [/SUP], Patricia Coelho[SUP] 1 [/SUP], Ananda S Mirchandani[SUP] 1 [/SUP], Ailiang Zhang[SUP] 1 [/SUP], David Hope[SUP] 3 [/SUP], Sarah K Clark[SUP] 3 [/SUP], Jo Singleton[SUP] 3 [/SUP], Shonna Johnston[SUP] 1 [/SUP], Robert Grecian[SUP] 1 [/SUP], Azin Poon[SUP] 1 [/SUP], Sarah McNamara[SUP] 1 [/SUP], Isla Harper[SUP] 1 [/SUP], Max Head Fourman[SUP] 3 [/SUP], Alejandro J Brenes[SUP] 2 4 [/SUP], Shalini Pathak[SUP] 2 [/SUP], Amy Lloyd[SUP] 2 [/SUP], Giovanny Rodriguez Blanco[SUP] 5 [/SUP], Alex von Kriegsheim[SUP] 5 [/SUP], Bart Ghesquiere[SUP] 6 [/SUP], Wesley Vermaelen[SUP] 6 [/SUP], Camila T Cologna[SUP] 6 [/SUP], Kevin Dhaliwal[SUP] 1 [/SUP], Nik Hirani[SUP] 1 7 [/SUP], David H Dockrell[SUP] 1 [/SUP], Moira K B Whyte[SUP] 1 [/SUP], David Griffith[SUP] 3 [/SUP], Doreen A Cantrell[SUP] 2 [/SUP], Sarah R Walmsley[SUP] 1 [/SUP]
Affiliations
Abstract
Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.
Keywords: ARDS; COVID-19; Neutrophil; SARS-CoV-2; Type I IFN; dexamethasone.
. 2021 Feb 22;6:38.
doi: 10.12688/wellcomeopenres.16584.1. eCollection 2021.
-------A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS--
Leila Reyes[SUP] #[/SUP][SUP] 1 [/SUP], Manuel A Sanchez-Garcia[SUP] #[/SUP][SUP] 1 [/SUP], Tyler Morrison[SUP] #[/SUP][SUP] 1 [/SUP], Andy J M Howden[SUP] #[/SUP][SUP] 2 [/SUP], Emily R Watts[SUP] 1 [/SUP], Simone Arienti[SUP] 1 [/SUP], Pranvera Sadiku[SUP] 1 [/SUP], Patricia Coelho[SUP] 1 [/SUP], Ananda S Mirchandani[SUP] 1 [/SUP], Ailiang Zhang[SUP] 1 [/SUP], David Hope[SUP] 3 [/SUP], Sarah K Clark[SUP] 3 [/SUP], Jo Singleton[SUP] 3 [/SUP], Shonna Johnston[SUP] 1 [/SUP], Robert Grecian[SUP] 1 [/SUP], Azin Poon[SUP] 1 [/SUP], Sarah McNamara[SUP] 1 [/SUP], Isla Harper[SUP] 1 [/SUP], Max Head Fourman[SUP] 3 [/SUP], Alejandro J Brenes[SUP] 2 4 [/SUP], Shalini Pathak[SUP] 2 [/SUP], Amy Lloyd[SUP] 2 [/SUP], Giovanny Rodriguez Blanco[SUP] 5 [/SUP], Alex von Kriegsheim[SUP] 5 [/SUP], Bart Ghesquiere[SUP] 6 [/SUP], Wesley Vermaelen[SUP] 6 [/SUP], Camila T Cologna[SUP] 6 [/SUP], Kevin Dhaliwal[SUP] 1 [/SUP], Nik Hirani[SUP] 1 7 [/SUP], David H Dockrell[SUP] 1 [/SUP], Moira K B Whyte[SUP] 1 [/SUP], David Griffith[SUP] 3 [/SUP], Doreen A Cantrell[SUP] 2 [/SUP], Sarah R Walmsley[SUP] 1 [/SUP]
Affiliations
- PMID: 33997298
- PMCID: PMC8112464
- DOI: 10.12688/wellcomeopenres.16584.1
Abstract
Background: Acute respiratory distress syndrome (ARDS) is a severe critical condition with a high mortality that is currently in focus given that it is associated with mortality caused by coronavirus disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS and there is also accumulating evidence of neutrophil mediated lung injury in patients who succumb to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Methods: We undertook a functional proteomic and metabolomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS and non-COVID-19 ARDS to understand the molecular basis of neutrophil dysregulation. Results: Expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in ARDS, irrespective of cause. Release of neutrophil granule proteins, neutrophil activation of the clotting cascade and upregulation of the Mac-1 platelet binding complex with formation of neutrophil platelet aggregates is exaggerated in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I interferon responses is seen in ARDS following infection with SARS-CoV-2, with associated rewiring of neutrophil metabolism, and the upregulation of antigen processing and presentation. Whilst dexamethasone treatment constricts the immature low density neutrophil population, it does not impact upon prothrombotic hyperinflammatory neutrophil signatures. Conclusions: Given the crucial role of neutrophils in ARDS and the evidence of a disordered myeloid response observed in COVID-19 patients, this work maps the molecular basis for neutrophil reprogramming in the distinct clinical entities of COVID-19 and non-COVID-19 ARDS.
Keywords: ARDS; COVID-19; Neutrophil; SARS-CoV-2; Type I IFN; dexamethasone.