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Abstract
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.
Original language | English |
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Article number | 38 |
Number of pages | 41 |
Journal | Wellcome Open Research |
Volume | 6 |
Early online date | 22 Feb 2021 |
DOIs | |
Publication status | Published - 20 May 2021 |
Keywords
- Neutrophil
- SARS-CoV-2
- COVID-19
- ARDS
- Type I IFN
- dexamethasone
- Dexamethasone
ASJC Scopus subject areas
- General Biochemistry,Genetics and Molecular Biology
- Medicine (miscellaneous)
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Dive into the research topics of 'A type I IFN, prothrombotic hyperinflammatory neutrophil signature is distinct for COVID-19 ARDS: [version 2; peer review: 2 approved, 2 approved with reservations]'. Together they form a unique fingerprint.Projects
- 1 Finished
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Rapid Research in Covid -19 Programme
Barrable, A. (Investigator), Belch, J. (Investigator), Boehnke, J. (Investigator), Booth, D. (Investigator), Brown, A. (Investigator), Cantrell, D. (Investigator), Chalmers, J. (Investigator), Coleman, S. (Investigator), Connell, D. (Investigator), Cuschieri, A. (Investigator), Dicker, A. (Investigator), Doney, A. (Investigator), Eftimie, R. (Investigator), Fang, M. (Investigator), Farre, A. (Investigator), Gamble, C. (Investigator), Howden, A. (Investigator), Krstajic, N. (Investigator), Lamond, A. (Investigator), Moraga Gonzalez, I. (Investigator), Palmer, C. (Investigator), Parcell, B. (Investigator), Pearson, E. (Investigator), Shoemark, A. (Investigator) & Sixsmith, J. (Investigator)
1/06/20 → 30/09/21
Project: Research