Inflammatory profiles across the spectrum of disease reveal a distinct role for GM-CSF in severe COVID-19
Ryan S. Thwaites, Ashley Sanchez Sevilla Uruchurtu, Matthew K. Siggins, Felicity Liew, Clark D Russell, Shona C Moore, Cameron J. Fairfield, Edwin Carter, Simon T. Abrams, Charlotte‐Eve Short, Thilipan Thaventhiran, Emma Bergstrom, Zoe Gardener, Stephanie Ascough, Christopher Chiu, Annemarie B Docherty, David Hunt, Yanick J. Crow, Tom Solomon, Graham P. Taylor, Lance Turtle, Ewen M Harrison, Jake Dunning, Malcolm G. Semple, J Kenneth Baillie, Peter JM Openshaw, on behalf of the ISARIC4C investigators, J. Kenneth Baillie, Malcolm G. Semple, Peter JM Openshaw, Beatrice Alex, Benjamin Bach, William Barclay, Debby Bogaert, Meera Chand, G Cooke, Annemarie B Docherty, Jake Dunning, Ana da Silva Filipe, Tom Fletcher, Christopher Green, Rishi K Gupta, Ewen M Harrison, Julian A. Hiscox, Antonia Ho, Peter Horby, Samreen Ijaz, Saye Khoo, Paul Klenerman, Andrew Law, Wei Shen Lim, Alexander J. Mentzer, Laura Merson, Alison Meynert, Mahdad Noursadeghi, Shona C Moore, Massimo Palmarini, Carlo Palmieri, William A. Paxton, Georgios Pollakis, Nicholas Price, Andrew Rambaut, David Robertson, Clark D Russell, Vanessa Sancho‐Shimizu, J T Scott, Thushan I. de Silva, Louise Sigfrid, Tom Solomon, Shiranee Sriskandan, David I. Stuart, Charlotte Summers, Richard S. Tedder, Emma C. Thomson, Roger Thompson AA, Ryan S. Thwaites, Lance Turtle, Maria Zambon, Hayley Hardwick, Chloe Donohue, Ruth Lyons, Fiona Griffiths, Wilna Oosthuyzen, Lisa Norman, Riinu Pius, Tom Drake, Cameron J. Fairfield, Stephen R Knight, Kenneth A McLean, Derek Murphy, Catherine A. Shaw, Jo Dalton, Michelle Girvan, Egle Saviciute, Stephanie Roberts, Janet Harrison, Laura Marsh, Marie Connor, Sophie Halpin, Clare Jackson
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.