Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
File(s)
Published version
Author(s)
Type
Journal Article
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.
Date Issued
2021-03-10
Date Acceptance
2021-03-05
Citation
Science Immunology, 2021, 6 (57), pp.1-17
ISSN
2470-9468
Publisher
American Association for the Advancement of Science
Start Page
1
End Page
17
Journal / Book Title
Science Immunology
Volume
6
Issue
57
Copyright Statement
© 2021, American Association for the Advancement of Science https://creativecommons.org/licenses/by/4.0/
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Sponsor
Wellcome Trust
Wellcome Trust
National Institute for Health Research
National Institute for Health Research
Medical Research Council (MRC)
UKRI MRC COVID-19 Rapid Response Call
UK Research and Innovation
UK Research and Innovation
National Institute for Health Research
Medical Research Council (MRC)
National Institute for Health Research
Medical Research Council (MRC)
Imperial College Healthcare NHS Trust- BRC Funding
Identifier
http://immunology.sciencemag.org/content/6/57/eabg9873.abstract
Grant Number
090382/Z/09/Z
090382/Z/09/Z
HPRU-2012-10064
NIHR200927
MC_PC_19078
MC_PC19025
9815274 MC_PC_19025
1257927
NIHR201385
MR/R502121/1
RDF04
MR/T50256X/1
RDC04
Publication Status
Published
Date Publish Online
2021-03-10