Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses
Systemic Perturbations in Amine and Kynurenine Metabolism Associated with Acute SARS-CoV-2 Infection and Inflammatory Cytokine Responses
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DOI：
10.1021/acs.jproteome.1c00052
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发表时间：
2021-03-16
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：
Lawler, Nathan G.;Gray, Nicola;Nicholson, Jeremy K.
我们对SARS-CoV-2（+）（n = 10）或SARS-CoV-2（-）（n = 49）参与者的血浆进行了定量代谢表型分析，同时进行了细胞因子/趋化因子分析。SARS-CoV-2阳性与独特的代谢表型相关，并表现出对感染的复杂全身反应，包括氨基酸和犬尿氨酸代谢途径的严重干扰。9种代谢物在血浆中升高，并与感染密切相关（喹啉酸、谷氨酸、烟酸、天冬氨酸、新蝶呤、犬尿氨酸、苯丙氨酸、3-羟基犬尿氨酸和牛磺酸; p < 0.05），而4种代谢物在感染中较低（色氨酸、组氨酸、吲哚-3-乙酸和瓜氨酸; p < 0.05）。该特征支持感染后的全身代谢表型转化，表明可能的神经毒性和神经破坏（3-羟基犬尿氨酸和喹啉酸升高）和肝功能障碍（Fischer比率降低和牛磺酸升高）。最后，我们报告了在疾病中观察到的关键代谢物变化与促炎细胞因子和趋化因子浓度之间的相关性，这些细胞因子和趋化因子显示出对SARS-CoV-2感染的强烈免疫代谢紊乱。
We performed quantitative metabolic phenotyping of blood plasma in parallel with cytokine/chemokine analysis from participants who were either SARS-CoV-2 (+) (n = 10) or SARS-CoV-2 (-) (n = 49). SARS-CoV-2 positivity was associated with a unique metabolic phenotype and demonstrated a complex systemic response to infection, including severe perturbations in amino acid and kynurenine metabolic pathways. Nine metabolites were elevated in plasma and strongly associated with infection (quinolinic acid, glutamic acid, nicotinic acid, aspartic acid, neopterin, kynurenine, phenylalanine, 3-hydroxykynurenine, and taurine; p < 0.05), while four metabolites were lower in infection (tryptophan, histidine, indole-3-acetic acid, and citrulline; p < 0.05). This signature supports a systemic metabolic phenoconversion following infection, indicating possible neurotoxicity and neurological disruption (elevations of 3-hydroxykynurenine and quinolinic acid) and liver dysfunction (reduction in Fischer's ratio and elevation of taurine). Finally, we report correlations between the key metabolite changes observed in the disease with concentrations of proinflammatory cytokines and chemokines showing strong immunometabolic disorder in response to SARS-CoV-2 infection.