SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes

被引：96

作者：

Li, Yijia ^{[1
,2
]}

Schneider, Alexis M. ^{[3
,4
]}

Mehta, Arnav ^{[2
,3
,5
,6
]}

Sade-Feldman, Moshe ^{[2
,3
,6
]}

Kays, Kyle R. ^{[2
]}

Gentili, Matteo ^{[3
]}

Charland, Nicole C. ^{[2
]}

Gonye, Anna L. K. ^{[2
,3
,6
]}

Gushterova, Irena ^{[2
,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, Kasidet ^{[2
,3
]}

Margolin, Justin D. ^{[2
]}

McKaig, Brenna N. ^{[2
]}

Parry, Blair A. ^{[2
]}

Rojas-Lopez, Maricarmen ^{[7
,8
]}

Russo, Brian C. ^{[7
,8
]}

Sharma, Nihaarika ^{[2
,3
]}

Tantivit, Jessica ^{[2
,3
,9
]}

Thomas, Molly F. ^{[2
,3
,9
]}

Regan, James ^{[1
]}

Flynn, James P. ^{[1
]}

Villani, Alexandra-Chloe ^{[2
,3
,9
]}

Hacohen, Nir ^{[2
,3
,6
]}

Goldberg, Marcia B. ^{[2
,3
,7
,8
]}

Filbin, Michael R. ^{[2
,3
]}

Li, Jonathan Z. ^{[1
]}

机构：

[1] Harvard Med Sch, Brigham & Womens Hosp, 65 Landsdowne St,Room 421, Boston, MA 02139 USA

[2] Harvard Med Sch, Massachusetts Gen Hosp, Boston, MA 02139 USA

[3] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[4] MIT, Dept Biol Engn, 77 Massachusetts Ave, Cambridge, MA 02139 USA

[5] Harvard Med Sch, Dana Farber Canc Inst, Boston, MA 02115 USA

[6] Massachusetts Gen Hosp, Dept Med, Ctr Canc Res, Boston, MA 02114 USA

[7] Massachusetts Gen Hosp, Dept Med, Ctr Bacterial Pathogenesis, Div Infect Dis, Boston, MA 02114 USA

[8] Harvard Med Sch, Dept Microbiol, Boston, MA 02115 USA

[9] Massachusetts Gen Hosp, Dept Med, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

来源：

JOURNAL OF CLINICAL INVESTIGATION | 2021年 / 131卷 / 13期

基金：

美国国家卫生研究院;

关键词：

VIRAL-RNA DETECTION; SPIKE PROTEIN; CORONAVIRUS; DISEASE; BLOOD;

D O I：

10.1172/JCI148635

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

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.

引用

页数：13

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