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

Science Immunology
Published
10 Mar 2021
Authors
Thwaites RS, Sanchez Sevilla Uruchurtu A, Siggins MK, Liew F, Russell CD, Moore SC, Fairfield C, Carter E, Abrams S, Short CE, 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, on behalf of ISARIC4C investigators.
DOI

10.1126/sciimmunol.abg9873

 

Abstract

Although 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 interleukin-6 (IL-6), CXCL10, and granulocyte-macrophage colony-stimulating factor (GM-CSF)] was 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 with 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.