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

• DOI: 10.1172/jci.insight.140327
• Publication Date: 2020-06-19T16:00:58Z
• Authors: Tiffany Thomas; Davide Stefanoni; Julie A. Reisz; Travis Nemkov; Lorenzo Bertolone; Richard O. Francis; Krystalyn E. Hudson; James C. Zimring; Kirk C. Hansen; Eldad A. Hod; Steven L. Spitalnik; Angelo D’Alessandro
• Keywords: Adult; Blood Glucose; Male; 0303 health sciences; Interleukin-6; Fatty Acids; COVID-19; Fatty Acids, Nonesterified; Creatine; 3. Good health; Betacoronavirus; 03 medical and health sciences; Case-Control Studies; Creatinine; Metabolome; Cystine; Humans; Metabolomics; Female; Amino Acids; Coronavirus Infections; Kynurenine; Aged

BACKGROUNDReprogramming of host metabolism supports viral pathogenesis by fueling viral proliferation, by providing, for example, free amino acids and fatty acids as building blocks.METHODSTo 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).RESULTSTargeted 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 (e.g., methionine sulfoxide, cystine), proteolysis, and renal dysfunction (e.g., 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 (i.e., IL-6 and C-reactive protein) and renal function (i.e., blood urea nitrogen).CONCLUSIONIn 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.FUNDINGBoettcher Foundation Webb-Waring Biomedical Research Award; National Institute of General and Medical Sciences, NIH; and National Heart, Lung, and Blood Institute, NIH.