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

10.1126/sciimmunol.abg9873

Science Immunology

10th March 2021

Contributing to research themes:

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.

Author list:

Affiliations:
1 National Heart and Lung Institute, Imperial College London, U.K.
2 University of Edinburgh Centre for Inflammation Research, Edinburgh, U.K.
3 Dept of Clinical Infection, Microbiology and Immunology, University of Liverpool, U.K.
4 Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, U.K.
5 Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular 15 Medicine, University of Edinburgh, Edinburgh, U.K.
6 Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
7 Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, U.K.
8 Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, U.K.
9 Tropical and infectious disease unit, Liverpool University Hospitals NHS Foundation Trust 20 (member of Liverpool Health Partners), U.K.
10 National Infection Service, Public Health England, London, UK
11 NIHR Health Protection Research Unit in Emerging and Zoonotic Infections, Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool, U.K.
12 Respiratory Medicine, Alder Hey Children’s Hospital, Liverpool, U.K.
13 Roslin Institute, University of Edinburgh, Edinburgh, U.K.
* joint corresponding authors

Authors:

Ryan S Thwaites¹, Ashley Sanchez¹ Sevilla Uruchurtu¹, Matthew K Siggins¹, Felicity Liew¹, Clark D Russell², Shona C Moore³, Cameron Fairfield⁴, Edwin Carter⁵, Simon Abrams³, Charlotte-Eve Short⁶, Thilipan Thaventhiran⁶, Emma Bergstrom⁶, Zoe Gardener⁶, Stephanie Ascough⁶, Christopher Chiu⁶, Annemarie B Docherty^4,7, David Hunt⁸, Yanick J Crow⁵, Tom Solomon³, Graham P Taylor⁶, Lance Turtle^3,9, Ewen M Harrison⁴, Jake Dunning¹⁰, Malcolm G Semple^11,12,*,J Kenneth Baillie^7,13,*, Peter JM Openshaw^1,* on behalf of the ISARIC4C investigators