| Literature DB >> 34196300 |
Yijia Li1,2, Alexis M Schneider3,4, Arnav Mehta2,3,5,6, Moshe Sade-Feldman2,3,6, Kyle R Kays2, Matteo Gentili3, Nicole C Charland2, Anna Lk Gonye2,3,6, Irena Gushterova2,3,6, Hargun K Khanna2, Thomas J LaSalle2,3,6, Kendall M Lavin-Parsons2, Brendan M Lilley2, Carl L Lodenstein2, Kasidet Manakongtreecheep2,3, Justin D Margolin2, Brenna N McKaig2, Blair A Parry2, Maricarmen Rojas-Lopez7,8, Brian C Russo7,8, Nihaarika Sharma2,3, Jessica Tantivit2,3,9, Molly F Thomas2,3,9, James Regan1, James P Flynn1, Alexandra-Chloé Villani2,3,9, Nir Hacohen2,3,6, Marcia B Goldberg2,3,7,8, Michael R Filbin2,3, Jonathan Z Li1.
Abstract
BACKGROUNDSARS-CoV-2 plasma viremia has been associated with severe disease and death in COVID-19 in small-scale cohort studies. The mechanisms behind this association remain elusive.METHODSWe evaluated the relationship between SARS-CoV-2 viremia, disease outcome, and inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using a quantitative reverse transcription PCR-based platform. Proteomic data were generated with Proximity Extension Assay using the Olink platform.RESULTSThis study included 300 participants with nucleic acid test-confirmed COVID-19. Plasma SARS-CoV-2 viremia levels at the time of presentation predicted adverse disease outcomes, with an adjusted OR of 10.6 (95% CI 4.4-25.5, P < 0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and 3.9 (95% CI 1.5-10.1, P = 0.006) for 28-day mortality. Proteomic analyses revealed prominent proteomic pathways associated with SARS-CoV-2 viremia, including upregulation of SARS-CoV-2 entry factors (ACE2, CTSL, FURIN), heightened markers of tissue damage to the lungs, gastrointestinal tract, and endothelium/vasculature, and alterations in coagulation pathways.CONCLUSIONThese results highlight the cascade of vascular and tissue damage associated with SARS-CoV-2 plasma viremia that underlies its ability to predict COVID-19 disease outcomes.FUNDINGMark and Lisa Schwartz; the National Institutes of Health (U19AI082630); the American Lung Association; the Executive Committee on Research at Massachusetts General Hospital; the Chan Zuckerberg Initiative; Arthur, Sandra, and Sarah Irving for the David P. Ryan, MD, Endowed Chair in Cancer Research; an EMBO Long-Term Fellowship (ALTF 486-2018); a Cancer Research Institute/Bristol Myers Squibb Fellowship (CRI2993); the Harvard Catalyst/Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH awards UL1TR001102 and UL1TR002541-01); and by the Harvard University Center for AIDS Research (National Institute of Allergy and Infectious Diseases, 5P30AI060354).Entities:
Keywords: COVID-19; Fibrosis; Infectious disease; Proteomics; Pulmonary surfactants
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Year: 2021 PMID： 34196300 PMCID： PMC8245177 DOI： 10.1172/JCI148635
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808