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Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19.
Sci Immunol. 2021 03 10; 6(57)SI

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.

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Authors+Show Affiliations

Thwaites RS
National Heart and Lung Institute, Imperial College London, U.K.
Sanchez Sevilla Uruchurtu A
National Heart and Lung Institute, Imperial College London, U.K.
Siggins MK
National Heart and Lung Institute, Imperial College London, U.K.
Liew F
National Heart and Lung Institute, Imperial College London, U.K.
Russell CD
University of Edinburgh Centre for Inflammation Research, Edinburgh, U.K.
Moore SC
Dept of Clinical Infection, Microbiology and Immunology, University of Liverpool, U.K.
Fairfield C
Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, U.K.
Carter E
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, U.K.
Abrams S
Dept of Clinical Infection, Microbiology and Immunology, University of Liverpool, U.K.
Short CE
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Thaventhiran T
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Bergstrom E
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Gardener Z
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Ascough S
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Chiu C
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Docherty AB
Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, U.K. Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, U.K.
Hunt D
Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, U.K.
Crow YJ
Centre for Genomic and Experimental Medicine, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, U.K.
Solomon T
Dept of Clinical Infection, Microbiology and Immunology, University of Liverpool, U.K.
Taylor GP
Department of Infectious Disease, Faculty of Medicine, Imperial College London, U.K.
Turtle L
Dept of Clinical Infection, Microbiology and Immunology, University of Liverpool, U.K. Tropical and infectious disease unit, Liverpool University Hospitals NHS Foundation Trust (member of Liverpool Health Partners), U.K.
Harrison EM
Centre for Medical Informatics, Usher Institute, University of Edinburgh, Edinburgh, U.K.
Dunning J
National Infection Service, Public Health England, London, UK.
Semple MG
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. M.G.Semple@liverpool.ac.uk j.k.baillie@ed.ac.uk p.openshaw@imperial.ac.uk. Respiratory Medicine, Alder Hey Children's Hospital, Liverpool, U.K.
Baillie JK
Intensive Care Unit, Royal Infirmary Edinburgh, Edinburgh, U.K. M.G.Semple@liverpool.ac.uk j.k.baillie@ed.ac.uk p.openshaw@imperial.ac.uk. Roslin Institute, University of Edinburgh, Edinburgh, U.K.
Openshaw PJ
National Heart and Lung Institute, Imperial College London, U.K. M.G.Semple@liverpool.ac.uk j.k.baillie@ed.ac.uk p.openshaw@imperial.ac.uk.
ISARIC4C investigators
No affiliation info available

MeSH

AdultAgedCOVID-19CytokinesFemaleHumansInflammationInfluenza A Virus, H1N1 SubtypeInfluenza, HumanMaleMiddle AgedSARS-CoV-2Severity of Illness Index

Pub Type(s)

Journal Article
Multicenter Study
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

33692097

Citation

Thwaites, Ryan S., et al. "Inflammatory Profiles Across the Spectrum of Disease Reveal a Distinct Role for GM-CSF in Severe COVID-19." Science Immunology, vol. 6, no. 57, 2021.
Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, et al. Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Sci Immunol. 2021;6(57).
Thwaites, R. S., Sanchez Sevilla Uruchurtu, A., Siggins, M. K., Liew, F., Russell, C. D., Moore, S. C., Fairfield, C., Carter, E., Abrams, S., Short, C. E., Thaventhiran, T., Bergstrom, E., Gardener, Z., Ascough, S., Chiu, C., Docherty, A. B., Hunt, D., Crow, Y. J., Solomon, T., ... Openshaw, P. J. (2021). Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. Science Immunology, 6(57). https://doi.org/10.1126/sciimmunol.abg9873
Thwaites RS, et al. Inflammatory Profiles Across the Spectrum of Disease Reveal a Distinct Role for GM-CSF in Severe COVID-19. Sci Immunol. 2021 03 10;6(57) PubMed PMID: 33692097.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19. AU - Thwaites,Ryan S, AU - Sanchez Sevilla Uruchurtu,Ashley, AU - Siggins,Matthew K, AU - Liew,Felicity, AU - Russell,Clark D, AU - Moore,Shona C, AU - Fairfield,Cameron, AU - Carter,Edwin, AU - Abrams,Simon, AU - Short,Charlotte-Eve, AU - Thaventhiran,Thilipan, AU - Bergstrom,Emma, AU - Gardener,Zoe, AU - Ascough,Stephanie, AU - Chiu,Christopher, AU - Docherty,Annemarie B, AU - Hunt,David, AU - Crow,Yanick J, AU - Solomon,Tom, AU - Taylor,Graham P, AU - Turtle,Lance, AU - Harrison,Ewen M, AU - Dunning,Jake, AU - Semple,Malcolm G, AU - Baillie,J Kenneth, AU - Openshaw,Peter Jm, AU - ,, PY - 2021/02/08/received PY - 2021/03/05/accepted PY - 2021/3/11/entrez PY - 2021/3/12/pubmed PY - 2021/3/19/medline JF - Science immunology JO - Sci Immunol VL - 6 IS - 57 N2 - 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. SN - 2470-9468 UR - https://www.unboundmedicine.com/medline/citation/33692097/Inflammatory_profiles_across_the_spectrum_of_disease_reveal_a_distinct_role_for_GM_CSF_in_severe_COVID_19_ DB - PRIME DP - Unbound Medicine ER -