Mary Wilson
Well-known member
Science Immunology 10 Mar 2021:
Vol. 6, Issue 57, eabg9873
DOI: 10.1126/sciimmunol.abg9873
Ryan S Thwaites[SUP]1[/SUP], Ashley Sanchez Sevilla Uruchurtu[SUP]1[/SUP], Matthew K Siggins[SUP]1[/SUP], Felicity Liew[SUP]1[/SUP], Clark D Russell[SUP]2[/SUP], Shona C Moore[SUP]3[/SUP], Cameron Fairfield[SUP]4[/SUP], Edwin Carter[SUP]5[/SUP], Simon Abrams[SUP]3[/SUP], Charlotte-Eve Short[SUP]6[/SUP],
Thilipan Thaventhiran[SUP]6[/SUP], Emma Bergstrom[SUP]6[/SUP], Zoe Gardener[SUP]6[/SUP], Stephanie Ascough[SUP]6[/SUP], Christopher Chiu[SUP]6[/SUP],
Annemarie B Docherty[SUP]4[/SUP],[SUP]7[/SUP], David Hunt[SUP]8[/SUP], Yanick J Crow[SUP]5[/SUP], Tom Solomon[SUP]3[/SUP], Graham P Taylor[SUP]6[/SUP], Lance Turtle[SUP]3[/SUP],[SUP]9[/SUP], Ewen M Harrison[SUP]4[/SUP], Jake Dunning[SUP]10[/SUP], Malcolm G Semple[SUP]11[/SUP],[SUP]12[/SUP],[SUP]*[/SUP], J Kenneth Baillie[SUP]7[/SUP],[SUP]13[/SUP],[SUP]*[/SUP], Peter JM Openshaw[SUP]1[/SUP],[SUP]*[/SUP]
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.
https://immunology.sciencemag.org/content/6/57/eabg9873
Vol. 6, Issue 57, eabg9873
DOI: 10.1126/sciimmunol.abg9873
Ryan S Thwaites[SUP]1[/SUP], Ashley Sanchez Sevilla Uruchurtu[SUP]1[/SUP], Matthew K Siggins[SUP]1[/SUP], Felicity Liew[SUP]1[/SUP], Clark D Russell[SUP]2[/SUP], Shona C Moore[SUP]3[/SUP], Cameron Fairfield[SUP]4[/SUP], Edwin Carter[SUP]5[/SUP], Simon Abrams[SUP]3[/SUP], Charlotte-Eve Short[SUP]6[/SUP],
Thilipan Thaventhiran[SUP]6[/SUP], Emma Bergstrom[SUP]6[/SUP], Zoe Gardener[SUP]6[/SUP], Stephanie Ascough[SUP]6[/SUP], Christopher Chiu[SUP]6[/SUP],
Annemarie B Docherty[SUP]4[/SUP],[SUP]7[/SUP], David Hunt[SUP]8[/SUP], Yanick J Crow[SUP]5[/SUP], Tom Solomon[SUP]3[/SUP], Graham P Taylor[SUP]6[/SUP], Lance Turtle[SUP]3[/SUP],[SUP]9[/SUP], Ewen M Harrison[SUP]4[/SUP], Jake Dunning[SUP]10[/SUP], Malcolm G Semple[SUP]11[/SUP],[SUP]12[/SUP],[SUP]*[/SUP], J Kenneth Baillie[SUP]7[/SUP],[SUP]13[/SUP],[SUP]*[/SUP], Peter JM Openshaw[SUP]1[/SUP],[SUP]*[/SUP]
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.
https://immunology.sciencemag.org/content/6/57/eabg9873