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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 on ....

United Kingdom , United States , City Of , La Jolla , Oxford Immunotech , Jeremyj Farrar , Quanterix Billerica , Nahoko Shindo , Milliporesigma Burlington , Ethics Review Committee , Imperial Biomedical Research Centre , Scotlanda Research Ethics Committee Ref , Oxfordc Research Ethics Committee , Material Access Committee , Zoonotic Infections At University Of Liverpool , Health Protection Research Unit , World Health Organization , Tissue Bank Ethics Committee Approval , Health Protection Research Senior Investigator , Liverpool Experimental Cancer Medicine Centre , Infections At Imperial College London , United Kingdom Coronavirus Immunology Consortium , National Institute For Health Research United Kingdom , Fulham Research Ethics Committee , Department For International Development , Melinda Gates Foundation ,