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

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..

Medienart:

Preprint

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

bioRxiv.org - (2023) vom: 22. Okt. Zur Gesamtaufnahme - year:2023

Sprache:

Englisch

Beteiligte Personen:

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

Links:

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Themen:

570
Biology

doi:

10.1101/2021.02.24.21252357

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

XBI020022395