Identification of serum metabolites enhancing inflammatory responses in COVID-19.
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.
Keywords
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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