SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.

SARS-CoV-2 RNAemia and proteomic trajectories inform prognostication in COVID-19 patients admitted to intensive care.
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DOI:
10.1038/s41467-021-23494-1
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发表时间:
2021-06-07
影响因子:
16.6
通讯作者:
Mayr M
Mayr M
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gutmann C;Takov K;Burnap SA;Singh B;Ali H;Theofilatos K;Reed E;Hasman M;Nabeebaccus A;Fish M;McPhail MJ;O'Gallagher K;Schmidt LE;Cassel C;Rienks M;Yin X;Auzinger G;Napoli S;Mujib SF;Trovato F;Sanderson B;Merrick B;Niazi U;Saqi M;Dimitrakopoulou K;Fernández-Leiro R;Braun S;Kronstein-Wiedemann R;Doores KJ;Edgeworth JD;Shah AM;Bornstein SR;Tonn T;Hayday AC;Giacca M;Shankar-Hari M;Mayr M

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预后特征为2019冠状病毒病(COVID-19)重症监护室(ICU)患者的风险分层提供信息。我们从住院的COVID-19患者(n = 123)、非COVID-19 ICU脓毒症患者(n = 25)和健康对照(n = 30)中获得了血液样本(n = 474)。当中和抗体应答较低时,在COVID-19 ICU患者的血浆或血清(RNAemia)中检测到严重急性呼吸综合征冠状病毒2型(SARS-CoV-2)RNA。RNA血症与较高的28天ICU死亡率相关(经年龄和性别校正的风险比[HR],1.84 [95%CI,1.22-2.77])。RNAemia在性能上与最好的蛋白质预测因子相当。甘露糖结合凝集素2和正五聚蛋白-3(PTX 3)是先天免疫系统补体途径的两种激活剂,与死亡率呈正相关。机器学习将“年龄,RNAemia”和“年龄,PTX 3”确定为与28天ICU死亡率相关的最佳二元特征。在纵向比较中,COVID-19 ICU患者具有与死亡率相关的独特蛋白质组学轨迹,许多肝源性蛋白质的恢复表明存活。最后,补体系统蛋白和半乳糖凝集素-3结合蛋白(LGALS 3BP)被确定为SARS-CoV-2刺突糖蛋白的相互作用伴侣。LGALS 3BP过表达在体外抑制刺突-假颗粒摄取和刺突诱导的细胞-细胞融合。在本文中,作者使用RT-qPCR和质谱分析了重症监护室(ICU)COVID-19患者和对照组的纵向血液样本。他们发现,病毒RNA和五聚环蛋白-3预测28天ICU死亡率,半乳糖凝集素-3结合蛋白是具有抗病毒特性的SARS-CoV-2刺突糖蛋白的相互作用伴侣。
Prognostic characteristics inform risk stratification in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19). We obtained blood samples (n = 474) from hospitalized COVID-19 patients (n = 123), non-COVID-19 ICU sepsis patients (n = 25) and healthy controls (n = 30). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in plasma or serum (RNAemia) of COVID-19 ICU patients when neutralizing antibody response was low. RNAemia is associated with higher 28-day ICU mortality (hazard ratio [HR], 1.84 [95% CI, 1.22–2.77] adjusted for age and sex). RNAemia is comparable in performance to the best protein predictors. Mannose binding lectin 2 and pentraxin-3 (PTX3), two activators of the complement pathway of the innate immune system, are positively associated with mortality. Machine learning identified ‘Age, RNAemia’ and ‘Age, PTX3’ as the best binary signatures associated with 28-day ICU mortality. In longitudinal comparisons, COVID-19 ICU patients have a distinct proteomic trajectory associated with mortality, with recovery of many liver-derived proteins indicating survival. Finally, proteins of the complement system and galectin-3-binding protein (LGALS3BP) are identified as interaction partners of SARS-CoV-2 spike glycoprotein. LGALS3BP overexpression inhibits spike-pseudoparticle uptake and spike-induced cell-cell fusion in vitro. Here the authors use RT-qPCR and mass spectrometry to analyze longitudinal blood samples from intensive care unit (ICU) COVID-19 patients and controls. They find that viral RNA and pentraxin-3 predict 28-day ICU mortality and that galectin-3-binding protein is an interaction partner of SARS-CoV-2 spike glycoprotein with antiviral properties.
DOI: 10.12688/wellcomeopenres.16002.2
发表时间: 2020
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DOI: 10.1074/mcp.ra120.002305
发表时间: 2021
期刊: Molecular & cellular proteomics : MCP
影响因子: --
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发表时间: 2020-12-14
期刊: Critical care (London, England)
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DOI: 10.1038/s41467-019-08810-0
发表时间: 2019-02-25
影响因子: 16.6
作者:
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