Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in CO...

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Autores principales:	Tao Li, Nianzhi Ning, Bo Li, Deyan Luo, Enqiang Qin, Wenjing Yu, Jianxin Wang, Guang Yang, Nan Nan, Zhili He, Ning Yang, Saisai Gong, Jiajia Li, Aixia Liu, Yakun Sun, Zhan Li, Tianye Jia, Jie Gao, Wang Zhang, Yanyu Huang, Jun Hou, Ying Xue, Deyu Li, Zhen Wei, Liangyan Zhang, Boan Li, Hui Wang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	COVID-19 metabolomics inflammation ornithine cycle SARS-CoV-2 Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/6547fa02fff64ab09d3076f2d220f9e3
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spelling	oai:doaj.org-article:6547fa02fff64ab09d3076f2d220f9e32021-12-03T06:32:15ZLongitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients1664-302X10.3389/fmicb.2021.723818https://doaj.org/article/6547fa02fff64ab09d3076f2d220f9e32021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fmicb.2021.723818/fullhttps://doaj.org/toc/1664-302XCOVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.Tao LiNianzhi NingBo LiDeyan LuoEnqiang QinWenjing YuJianxin WangGuang YangNan NanZhili HeNing YangSaisai GongJiajia LiAixia LiuYakun SunZhan LiTianye JiaJie GaoWang ZhangYanyu HuangJun HouYing XueDeyu LiZhen WeiLiangyan ZhangBoan LiHui WangFrontiers Media S.A.articleCOVID-19metabolomicsinflammationornithine cycleSARS-CoV-2MicrobiologyQR1-502ENFrontiers in Microbiology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	COVID-19 metabolomics inflammation ornithine cycle SARS-CoV-2 Microbiology QR1-502
spellingShingle	COVID-19 metabolomics inflammation ornithine cycle SARS-CoV-2 Microbiology QR1-502 Tao Li Nianzhi Ning Bo Li Deyan Luo Enqiang Qin Wenjing Yu Jianxin Wang Guang Yang Nan Nan Zhili He Ning Yang Saisai Gong Jiajia Li Aixia Liu Yakun Sun Zhan Li Tianye Jia Jie Gao Wang Zhang Yanyu Huang Jun Hou Ying Xue Deyu Li Zhen Wei Liangyan Zhang Boan Li Hui Wang Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
description	COVID-19 is a severe disease in humans, as highlighted by the current global pandemic. Several studies about the metabolome of COVID-19 patients have revealed metabolic disorders and some potential diagnostic markers during disease progression. However, the longitudinal changes of metabolomics in COVID-19 patients, especially their association with disease progression, are still unclear. Here, we systematically analyzed the dynamic changes of the serum metabolome of COVID-19 patients, demonstrating that most of the metabolites did not recover by 1–3 days before discharge. A prominent signature in COVID-19 patients comprised metabolites of amino acids, peptides, and analogs, involving nine essential amino acids, 10 dipeptides, and four N-acetylated amino acids. The levels of 12 metabolites in amino acid metabolism, especially three metabolites of the ornithine cycle, were significantly higher in severe patients than in mild ones, mainly on days 1–3 or 4–6 since onset. Integrating blood metabolomic, biochemical, and cytokine data, we uncovered a highly correlated network, including 6 cytokines, 13 biochemical parameters, and 49 metabolites. Significantly, five ornithine cycle-related metabolites (ornithine, N-acetylornithine, 3-amino-2-piperidone, aspartic acid, and asparagine) highly correlated with “cytokine storms” and coagulation index. We discovered that the ornithine cycle dysregulation significantly correlated with inflammation and coagulation in severe patients, which may be a potential mechanism of COVID-19 pathogenicity. Our study provided a valuable resource for detailed exploration of metabolic factors in COVID-19 patients, guiding metabolic recovery, understanding the pathogenic mechanisms, and creating drugs against SARS-CoV-2 infection.
format	article
author	Tao Li Nianzhi Ning Bo Li Deyan Luo Enqiang Qin Wenjing Yu Jianxin Wang Guang Yang Nan Nan Zhili He Ning Yang Saisai Gong Jiajia Li Aixia Liu Yakun Sun Zhan Li Tianye Jia Jie Gao Wang Zhang Yanyu Huang Jun Hou Ying Xue Deyu Li Zhen Wei Liangyan Zhang Boan Li Hui Wang
author_facet	Tao Li Nianzhi Ning Bo Li Deyan Luo Enqiang Qin Wenjing Yu Jianxin Wang Guang Yang Nan Nan Zhili He Ning Yang Saisai Gong Jiajia Li Aixia Liu Yakun Sun Zhan Li Tianye Jia Jie Gao Wang Zhang Yanyu Huang Jun Hou Ying Xue Deyu Li Zhen Wei Liangyan Zhang Boan Li Hui Wang
author_sort	Tao Li
title	Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
title_short	Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
title_full	Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
title_fullStr	Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
title_full_unstemmed	Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients
title_sort	longitudinal metabolomics reveals ornithine cycle dysregulation correlates with inflammation and coagulation in covid-19 severe patients
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/6547fa02fff64ab09d3076f2d220f9e3
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Longitudinal Metabolomics Reveals Ornithine Cycle Dysregulation Correlates With Inflammation and Coagulation in COVID-19 Severe Patients

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