SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes
SARS-CoV-2 viremia is associated with distinct proteomic pathways and predicts COVID-19 outcomes
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DOI：
10.1172/jci148635
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发表时间：
2021-07-01
影响因子：
15.9
通讯作者：
Li, Jonathan Z.
中科院分区：
文献类型：
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作者：
Li, Yijia;Schneider, Alexis M.;Li, Jonathan Z.
背景。在小规模队列研究中，SARS-CoV-2血浆病毒血症与COVID-19患者的严重疾病和死亡有关。这种关联背后的机制仍然难以捉摸。方法。我们评估了COVID-19急诊科参与者队列中SARS-CoV-2病毒血症、疾病结局、炎症和蛋白质组学特征之间的关系。使用基于定量逆转录pcr的平台测量SARS-CoV-2病毒载量。蛋白质组学数据通过使用Olink平台的接近扩展分析生成。结果。本研究纳入了300名核酸检测确诊的新冠肺炎患者。发病时血浆SARS-CoV-2病毒血症水平预测不良疾病结局，严重疾病（机械通气和/或28天死亡率）的调整OR为10.6 (95% CI 4.4-25.5, P < 0.001)， 28天死亡率的调整OR为3.9 （95% CI 1.5-10.1, P = 0.006）。蛋白质组学分析揭示了与SARS-CoV-2病毒血症相关的重要蛋白质组学途径，包括SARS-CoV-2进入因子（ACE2、CTSL、FURIN）的上调，肺、胃肠道和内皮/血管组织损伤标志物的升高，以及凝血途径的改变。结论。这些结果强调了与SARS-CoV-2血浆病毒血症相关的血管和组织损伤级联反应，这是其预测COVID-19疾病结局能力的基础。
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.