Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection
Integrative Modeling of Quantitative Plasma Lipoprotein, Metabolic, and Amino Acid Data Reveals a Multiorgan Pathological Signature of SARS-CoV-2 Infection
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DOI：
10.1021/acs.jproteome.0c00519
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发表时间：
2020-11-06
影响因子：
4.4
通讯作者：
Nicholson, Jeremy K.
中科院分区：
文献类型：
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作者：
Kimhofer, Torben;Lodge, Samantha;Nicholson, Jeremy K.
采用核磁共振（NMR）和液相色谱-质谱（LC-MS）多平台代谢表型分析方法，研究了严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染对人血浆代谢的影响。对SARS-CoV-2病毒检测呈阳性的症状性冠状病毒19 （COVID-19）患者（n = 17）和年龄和性别匹配的对照组（n = 25）的样本进行了脂蛋白亚组分、α -1-酸性糖蛋白、葡萄糖和生物原胺的定量测量。使用正交隐结构投影（OPLS）方法对数据进行分析，并用于构建异常强（AUROC = 1）的混合核磁共振-质谱模型，该模型能够详细区分各组之间的代谢及其生化关系。关键的鉴别代谢物包括炎症标志物，包括α -1-酸性糖蛋白升高和犬尿氨酸/色氨酸比值升高。还有与糖尿病和冠状动脉疾病一致的脂蛋白、葡萄糖和氨基酸异常（低总和HDL载脂蛋白A1，低HDL甘油三酯，高LDL和VLDL甘油三酯），以及多种高度显著的肝功能障碍氨基酸标志物（包括谷氨酰胺/谷氨酸和Fischer比值升高），这些标志物表现为独特的SARS-CoV-2感染模式的一部分。使用来自其他SARS-CoV-2阳性患者和对照组的独立样本验证了多变量训练测试集模型。该预测模型对SARS-CoV-2阳性的敏感性为100%。受干扰通路的广度表明SARS-CoV-2阳性的系统性特征，包括肝功能障碍、血脂异常、糖尿病和冠心病风险，这与最近的报道一致，即COVID-19是一种影响多器官和系统的全身性疾病。
The metabolic effects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on human blood plasma were characterized using multiplatform metabolic phenotyping with nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS). Quantitative measurements of lipoprotein subfractions, alpha-1-acid glycoprotein, glucose, and biogenic amines were made on samples from symptomatic coronavirus disease 19 (COVID-19) patients who had tested positive for the SARS-CoV-2 virus (n = 17) and from age- and gender-matched controls (n = 25). Data were analyzed using an orthogonal-projections to latent structures (OPLS) method and used to construct an exceptionally strong (AUROC = 1) hybrid NMR-MS model that enabled detailed metabolic discrimination between the groups and their biochemical relationships. Key discriminant metabolites included markers of inflammation including elevated alpha-1-acid glycoprotein and an increased kynurenine/tryptophan ratio. There was also an abnormal lipoprotein, glucose, and amino acid signature consistent with diabetes and coronary artery disease (low total and HDL Apolipoprotein A1, low HDL triglycerides, high LDL and VLDL triglycerides), plus multiple highly significant amino acid markers of liver dysfunction (including the elevated glutamine/glutamate and Fischer's ratios) that present themselves as part of a distinct SARS-CoV-2 infection pattern. A multivariate training-test set model was validated using independent samples from additional SARS-CoV-2 positive patients and controls. The predictive model showed a sensitivity of 100% for SARS-CoV-2 positivity. The breadth of the disturbed pathways indicates a systemic signature of SARS-CoV-2 positivity that includes elements of liver dysfunction, dyslipidemia, diabetes, and coronary heart disease risk that are consistent with recent reports that COVID-19 is a systemic disease affecting multiple organs and systems.