[HTML][HTML] COVID-19 infection alters kynurenine and fatty acid metabolism, correlating with IL-6 levels and renal status

T Thomas, D Stefanoni, JA Reisz, T Nemkov… - JCI insight, 2020 - ncbi.nlm.nih.gov
T Thomas, D Stefanoni, JA Reisz, T Nemkov, L Bertolone, RO Francis, KE Hudson
JCI insight, 2020ncbi.nlm.nih.gov
BACKGROUND Reprogramming of host metabolism supports viral pathogenesis by fueling
viral proliferation, by providing, for example, free amino acids and fatty acids as building
blocks. METHODS To investigate metabolic effects of SARS-CoV-2 infection, we evaluated
serum metabolites of patients with COVID-19 (n= 33; diagnosed by nucleic acid testing), as
compared with COVID-19–negative controls (n= 16). RESULTS Targeted and untargeted
metabolomics analyses identified altered tryptophan metabolism into the kynurenine …
Abstract
BACKGROUND
Reprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.
METHODS
To investigate metabolic effects of SARS-CoV-2 infection, we evaluated serum metabolites of patients with COVID-19 (n= 33; diagnosed by nucleic acid testing), as compared with COVID-19–negative controls (n= 16).
RESULTS
Targeted and untargeted metabolomics analyses identified altered tryptophan metabolism into the kynurenine pathway, which regulates inflammation and immunity. Indeed, these changes in tryptophan metabolism correlated with interleukin-6 (IL-6) levels. Widespread dysregulation of nitrogen metabolism was also seen in infected patients, with altered levels of most amino acids, along with increased markers of oxidant stress (eg, methionine sulfoxide, cystine), proteolysis, and renal dysfunction (eg, creatine, creatinine, polyamines). Increased circulating levels of glucose and free fatty acids were also observed, consistent with altered carbon homeostasis. Interestingly, metabolite levels in these pathways correlated with clinical laboratory markers of inflammation (ie, IL-6 and C-reactive protein) and renal function (ie, blood urea nitrogen).
CONCLUSION
In conclusion, this initial observational study identified amino acid and fatty acid metabolism as correlates of COVID-19, providing mechanistic insights, potential markers of clinical severity, and potential therapeutic targets.
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