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Identification of serum metabolites enhancing inflammatory responses in COVID-19.
Zhang, Chen-Song; Zhang, Bingchang; Li, Mengqi; Wei, Xiaoyan; Gong, Kai; Li, Zhiyong; Yao, Xiangyang; Wu, Jianfeng; Zhang, Cixiong; Zhu, Mingxia; Zhang, Lei; Sun, Xiufeng; Zhan, Yi-Hong; Jiang, Zhengye; Zhao, Wenpeng; Zhong, Wei; Zhuang, Xinguo; Zhou, Dawang; Piao, Hai-Long; Lin, Sheng-Cai; Wang, Zhanxiang.
  • Zhang CS; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Zhang B; Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Li M; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Wei X; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Gong K; Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Li Z; Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Yao X; Department of pulmonary diseases, The First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Wu J; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Zhang C; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Zhu M; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Zhang L; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Sun X; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Zhan YH; Department of Neurosurgery, Xiamen Key Laboratory of Brain Center, the First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Jiang Z; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Zhao W; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Zhong W; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Zhuang X; Department of Laboratory Medicine, The First Affiliated Hospital of Xiamen University, Xiamen, 361102, China.
  • Zhou D; School of Medicine, Xiamen University, Xiamen, 361102, China.
  • Piao HL; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China.
  • Lin SC; Scientific Research Center for Translational Medicine, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
  • Wang Z; State Key Laboratory for Cellular Stress Biology, School of Life Sciences, Xiamen University, Xiamen, 361102, China. linsc@xmu.edu.cn.
Sci China Life Sci ; 65(10): 1971-1984, 2022 10.
Article in English | MEDLINE | ID: covidwho-1826874
ABSTRACT
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is characterized by a strong production of inflammatory cytokines such as TNF and IL-6, which underlie the severity of the disease. However, the molecular mechanisms responsible for such a strong immune response remains unclear. Here, utilizing targeted tandem mass spectrometry to analyze serum metabolome and lipidome in COVID-19 patients at different temporal stages, we identified that 611 metabolites (of 1,039) were significantly altered in COVID-19 patients. Among them, two metabolites, agmatine and putrescine, were prominently elevated in the serum of patients; and 2-quinolinecarboxylate was changed in a biphasic manner, elevated during early COVID-19 infection but levelled off. When tested in mouse embryonic fibroblasts (MEFs) and macrophages, these 3 metabolites were found to activate the NF-κB pathway that plays a pivotal role in governing cytokine production. Importantly, these metabolites were each able to cause strong increase of TNF and IL-6 levels when administered to wildtype mice, but not in the mice lacking NF-κB. Intriguingly, these metabolites have little effects on the activation of interferon regulatory factors (IRFs) for the production of type I interferons (IFNs) for antiviral defenses. These data suggest that circulating metabolites resulting from COVID-19 infection may act as effectors to elicit the peculiar systemic inflammatory responses, exhibiting severely strong proinflammatory cytokine production with limited induction of the interferons. Our study may provide a rationale for development of drugs to alleviate inflammation in COVID-19 patients.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / Agmatine / COVID-19 Type of study: Prognostic study Limits: Animals Language: English Journal: Sci China Life Sci Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S11427-021-2099-7

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Interferon Type I / Agmatine / COVID-19 Type of study: Prognostic study Limits: Animals Language: English Journal: Sci China Life Sci Journal subject: Biology / Science Year: 2022 Document Type: Article Affiliation country: S11427-021-2099-7