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.


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.

Cite as

Thwaites, R., Uruchurtu, A., Siggins, M., Liew, F., Russell, C., Moore, S., Fairfield, C., Carter, E., Abrams, S., Short, C., Thaventhiran, T., Bergstrom, E., Gardener, Z., Ascough, S., Chiu, C., Docherty, A., Hunt, D., Crow, J., Solomon, T., Taylor , G., Turtle, L., Harrison, E., Dunning, J., Semple, M., Baillie, J., Openshaw, P. & 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), article no: eabg9873. https://doi.org/10.1126/sciimmunol.abg9873

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Last updated: 23 May 2024
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