Author: Li, Y.; Schneider, A. M.; Mehta, A.; Sade-Feldman, M.; Kays, K. R.; Gentili, M.; Charland, N. C.; Gonye, A. L.; Gushterova, I.; Khanna, H. K.; LaSalle, T. J.; Lavin-Parsons, K. M.; Lilley, B. M.; Lodenstein, C. L.; Manakongtreecheep, K.; Margolin, J. D.; McKaig, B. N.; Parry, B. A.; Rojas-Lopez, M.; Russo, B. C.; Sharma, N.; Tantivit, J.; Thomas, M. F.; Regan, J.; Flynn, J. P.; Villani, A.-C.; Hacohen, N.; Goldberg, M. B.; Filbin, M. R.; Li, J. Z.
Title: SARS-CoV-2 Viremia is Associated with Distinct Proteomic Pathways and Predicts COVID-19 Outcomes Cord-id: ad7nrdax Document date: 2021_2_26
ID: ad7nrdax
Snippet: Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive. Methods: We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based pla
Document: Background: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) plasma viremia has been associated with severe disease and death in coronavirus disease 2019 (COVID-19) in small-scale cohort studies. The mechanisms behind this association remain elusive. Methods: We evaluated the relationship between SARS-CoV-2 viremia, disease outcome, inflammatory and proteomic profiles in a cohort of COVID-19 emergency department participants. SARS-CoV-2 viral load was measured using qRT-PCR based platform. Proteomic data were generated with Proximity Extension Assay (PEA) using the Olink platform. Results: Three hundred participants with nucleic acid test-confirmed COVID-19 were included in this study. Levels of plasma SARS-CoV-2 viremia at the time of presentation predicted adverse disease outcomes, with an adjusted odds ratio (aOR) of 10.6 (95% confidence interval [CI] 4.4, 25.5, P<0.001) for severe disease (mechanical ventilation and/or 28-day mortality) and aOR of 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, endothelium/vasculature and alterations in coagulation pathways. Conclusions: These 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.
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