التفاصيل البيبلوغرافية
| العنوان: |
SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes. |
| المؤلفون: |
Yijia Li1,2, Schneider, Alexis M.3,4, Mehta, Arnav2,3,5,6, Sade-Feldman, Moshe2,3,6, Kays, Kyle R.2, Gentili, Matteo3, Charland, Nicole C.2, Gonye, Anna L. K.2,3,6, Gushterova, Irena2,3,6, Khanna, Hargun K.2, LaSalle, Thomas J.2,3,6, Lavin-Parsons, Kendall M.2, Lilley, Brendan M.2, Lodenstein, Carl L.2, Manakongtreecheep, Kasidet2,3, Margolin, Justin D.2, McKaig, Brenna N.2, Parry, Blair A.2, Rojas-Lopez, Maricarmen7,8, Russo, Brian C.7,8 |
| المصدر: |
Journal of Clinical Investigation. 7/1/2021, Vol. 131 Issue 13, p1-12. 12p. |
| مصطلحات موضوعية: |
*SARS-CoV-2, *COVID-19, *COVID-19 pandemic, *PROTEOMICS, *VIREMIA |
| الشركة/الكيان: |
NATIONAL Institutes of Health (U.S.) , NATIONAL Institute of Allergy & Infectious Diseases (U.S.) , MASSACHUSETTS General Hospital |
| مستخلص: |
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). [ABSTRACT FROM AUTHOR] |
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