Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
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 recru...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Other Authors: | |
| Format: | Journal article |
| Language: | English |
| Published: |
American Association for the Advancement of Science
2021
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| _version_ | 1797105056210747392 |
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| author | Thwaites, RS Sanchez Sevilla Uruchurtu, A Siggins, MK Liew, F Russell, CD Moore, SC Fairfield, C Carter, E Abrams, S Short, C-E Thaventhiran, T Bergstrom, E Gardener, Z Ascough, S Chiu, C Docherty, AB Hunt, D Crow, YJ Solomon, T Taylor, GP Turtle, L Harrison, EM Dunning, J Semple, MG Baillie, JK Openshaw, PJ |
| author2 | ISARIC4C investigators |
| author_facet | ISARIC4C investigators Thwaites, RS Sanchez Sevilla Uruchurtu, A Siggins, MK Liew, F Russell, CD Moore, SC Fairfield, C Carter, E Abrams, S Short, C-E Thaventhiran, T Bergstrom, E Gardener, Z Ascough, S Chiu, C Docherty, AB Hunt, D Crow, YJ Solomon, T Taylor, GP Turtle, L Harrison, EM Dunning, J Semple, MG Baillie, JK Openshaw, PJ |
| author_sort | Thwaites, RS |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T06:42:06Z |
| format | Journal article |
| id | oxford-uuid:f9a6593f-751a-49b2-bd78-89cba7bb2757 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T06:42:06Z |
| publishDate | 2021 |
| publisher | American Association for the Advancement of Science |
| record_format | dspace |
| spelling | oxford-uuid:f9a6593f-751a-49b2-bd78-89cba7bb27572022-03-27T12:59:41ZInflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:f9a6593f-751a-49b2-bd78-89cba7bb2757EnglishSymplectic ElementsAmerican Association for the Advancement of Science2021Thwaites, RSSanchez Sevilla Uruchurtu, ASiggins, MKLiew, FRussell, CDMoore, SCFairfield, CCarter, EAbrams, SShort, C-EThaventhiran, TBergstrom, EGardener, ZAscough, SChiu, CDocherty, ABHunt, DCrow, YJSolomon, TTaylor, GPTurtle, LHarrison, EMDunning, JSemple, MGBaillie, JKOpenshaw, PJISARIC4C investigatorsWhile 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. |
| spellingShingle | Thwaites, RS Sanchez Sevilla Uruchurtu, A Siggins, MK Liew, F Russell, CD Moore, SC Fairfield, C Carter, E Abrams, S Short, C-E Thaventhiran, T Bergstrom, E Gardener, Z Ascough, S Chiu, C Docherty, AB Hunt, D Crow, YJ Solomon, T Taylor, GP Turtle, L Harrison, EM Dunning, J Semple, MG Baillie, JK Openshaw, PJ Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title | Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title_full | Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title_fullStr | Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title_full_unstemmed | Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title_short | Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19 |
| title_sort | inflammatory profiles across the spectrum of disease reveal a distinct role for gm csf in severe covid 19 |
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