SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes
Name
148635.1-20210621121059-covered-4fa089109ce452e764bbb8648b44a723.pdf
Description
Published version
Size
3.42 MB
Format
Adobe PDF
Checksum (MD5)
36f250fa09c2256ef0e50d7107448504
Date Issued
July 1, 2021
Journal
Journal of Clinical Investigation
Publisher
American Society for Clinical Investigation
Version
Final published version
Abstract
BACKGROUND. SARS-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.
METHODS. We 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.
RESULTS. This 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.
CONCLUSION. 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.
FUNDING. Mark 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).
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DOI of Published Version
https://doi.org/10.1172/jci148635
