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基于 H qNMR 的代谢组学区分新冠病毒感染严重程度。

H qNMR-Based Metabolomics Discrimination of Covid-19 Severity.

机构信息

Instituto de Química de São Carlos, Universidade de São Paulo, São Carlos, SP 13566-590, Brazil.

Instituto Nacional de Ciência e Tecnologia de Bioanalítica, INCTBio, Campinas, SP 13083-861, Brazil.

出版信息

J Proteome Res. 2022 Jul 1;21(7):1640-1653. doi: 10.1021/acs.jproteome.1c00977. Epub 2022 Jun 8.

Abstract

The coronavirus disease 2019 (Covid-19), which caused respiratory problems in many patients worldwide, led to more than 5 million deaths by the end of 2021. Experienced symptoms vary from mild to severe illness. Understanding the infection severity to reach a better prognosis could be useful to the clinics, and one study area to fulfill one piece of this biological puzzle is metabolomics. The metabolite profile and/or levels being monitored can help predict phenotype properties. Therefore, this study evaluated plasma metabolomes of 110 individual samples, 57 from control patients and 53 from recent positive cases of Covid-19 (IgM 98% reagent), representing mild to severe symptoms, before any clinical intervention. Polar metabolites from plasma samples were analyzed by quantitative H NMR. Glycerol, 3-aminoisobutyrate, formate, and glucuronate levels showed alterations in Covid-19 patients compared to those in the control group (Tukey's HSD -value cutoff = 0.05), affecting the lactate, phenylalanine, tyrosine, and tryptophan biosynthesis and d-glutamine, d-glutamate, and glycerolipid metabolisms. These metabolic alterations show that SARS-CoV-2 infection led to disturbance in the energetic system, supporting the viral replication and corroborating with the severe clinical conditions of patients. Six polar metabolites (glycerol, acetate, 3-aminoisobutyrate, formate, glucuronate, and lactate) were revealed by PLS-DA and predicted by ROC curves and ANOVA to be potential prognostic metabolite panels for Covid-19 and considered clinically relevant for predicting infection severity due to their straight roles in the lipid and energy metabolism. Thus, metabolomics from samples of Covid-19 patients is a powerful tool for a better understanding of the disease mechanism of action and metabolic consequences of the infection in the human body and may corroborate allowing clinicians to intervene quickly according to the needs of Covid-19 patients.

摘要

2019 年冠状病毒病(COVID-19)在全球范围内导致许多患者出现呼吸道问题,到 2021 年底已导致超过 500 万人死亡。患者的症状从轻度到重度不等。了解感染的严重程度以达到更好的预后对临床医生可能有用,而代谢组学是一个可以帮助解决这一生物学难题的研究领域。监测代谢物的特征和/或水平有助于预测表型特征。因此,本研究评估了 110 个个体样本的血浆代谢组学,其中 57 个来自对照患者,53 个来自 COVID-19(IgM 试剂 98%)的近期阳性病例,代表了从轻到重的症状,在任何临床干预之前。通过定量 H NMR 分析血浆样品中的极性代谢物。与对照组相比,COVID-19 患者的甘油、3-氨基异丁酸、甲酸盐和葡萄糖醛酸盐水平发生了变化(Tukey HSD 值截止值=0.05),影响了乳酸、苯丙氨酸、酪氨酸和色氨酸的生物合成以及 d-谷氨酸、d-谷氨酸盐和甘油脂代谢。这些代谢变化表明,SARS-CoV-2 感染导致能量系统紊乱,支持病毒复制,并与患者的严重临床状况相符。通过 PLS-DA 揭示了 6 种极性代谢物(甘油、醋酸盐、3-氨基异丁酸、甲酸盐、葡萄糖醛酸盐和乳酸),通过 ROC 曲线和 ANOVA 预测其为 COVID-19 的潜在预后代谢物组,并考虑到它们在脂质和能量代谢中的直接作用,具有临床相关性,可用于预测感染严重程度。因此,COVID-19 患者样本的代谢组学是更好地了解疾病作用机制和感染对人体代谢影响的有力工具,并可能有助于临床医生根据 COVID-19 患者的需要迅速进行干预。

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