Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.

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Thwaites, Ryan S, Sanchez Sevilla Uruchurtu, Ashley, Siggins, Matthew K, Liew, Felicity, Russell, Clark D, Moore, Shona C ORCID: 0000-0001-8610-2806, Fairfield, Cameron, Carter, Edwin, Abrams, Simon, Short, Charlotte-Eve et al (show 17 more authors) , Thaventhiran, Thilipan, Bergstrom, Emma, Gardener, Zoe, Ascough, Stephanie, Chiu, Christopher, Docherty, Annemarie B, Hunt, David, Crow, Yanick J, Solomon, Tom ORCID: 0000-0001-7266-6547, Taylor, Graham P, Turtle, Lance ORCID: 0000-0002-0778-1693, Harrison, Ewen M, Dunning, Jake, Semple, Malcolm G ORCID: 0000-0001-9700-0418, Baillie, J Kenneth, Openshaw, Peter Jm and ISARIC4C investigators, (2021) Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Science Immunology, 6 (57). eabg9873-.

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Abstract

While it is now widely accepted that host inflammatory responses contribute to lung injury, the pathways that drive severity and distinguish coronavirus disease 2019 (COVID-19) from other viral lung diseases remain poorly characterized. We analyzed plasma samples from 471 hospitalized patients recruited through the prospective multicenter ISARIC4C study and 39 outpatients with mild disease, enabling extensive characterization of responses across a full spectrum of COVID-19 severity. Progressive elevation of levels of numerous inflammatory cytokines and chemokines (including IL-6, CXCL10, and GM-CSF) were associated with severity and accompanied by elevated markers of endothelial injury and thrombosis. Principal component and network analyses demonstrated central roles for IL-6 and GM-CSF in COVID-19 pathogenesis. Comparing these profiles to archived samples from patients with fatal influenza, IL-6 was equally elevated in both conditions whereas GM-CSF was prominent only in COVID-19. These findings further identify the key inflammatory, thrombotic, and vascular factors that characterize and distinguish severe and fatal COVID-19.

Item Type:	Article
Uncontrolled Keywords:	ISARIC4C investigators
Divisions:	Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Infection, Veterinary and Ecological Sciences
Depositing User:	Symplectic Admin
Date Deposited:	09 Apr 2021 08:00
Last Modified:	18 Jan 2023 22:56
DOI:	10.1126/sciimmunol.abg9873
Open Access URL:	http://doi.org/10.1126/sciimmunol.abg9873
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3117588