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[Preprint]. 2021 Feb 26:2021.02.24.21252357. [Version 1] doi: 10.1101/2021.02.24.21252357

SARS-CoV-2 Viremia is Associated with Distinct Proteomic Pathways and Predicts COVID-19 Outcomes

Yijia Li, Alexis M Schneider, Arnav Mehta, Moshe Sade-Feldman, Kyle R Kays, Matteo Gentili, Nicole C Charland, Anna LK Gonye, Irena Gushterova, Hargun K Khanna, Thomas J LaSalle, Kendall M Lavin-Parsons, Brendan M Lilly, Carl L Lodenstein, Kasidet Manakongtreecheep, Justin D Margolin, Brenna N McKaig, Blair A Parry, Maricarmen Rojas-Lopez, Brian C Russo, Nihaarika Sharma, Jessica Tantivit, Molly F Thomas, James Regan, James P Flynn, Alexandra-Chloé Villani, Nir Hacohen, Marcia B Goldberg, Michael R Filbin, Jonathan Z Li
PMCID: PMC7924277  PMID: 33655257

Abstract

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.

Full Text Availability

The license terms selected by the author(s) for this preprint version do not permit archiving in PMC. The full text is available from the preprint server.


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