Peripheral kynurenines as biomarkers and targets for prevention and treatment of psychiatric conditions associated with SARS-CoV-2 infection

Abstract

Present review focuses on the possible role of tryptophan (Trp) – kynurenine (Kyn) pathway in the mechanism(s) of COVID-19 associated psychiatric complications. SARS-CoV-2 infection, that causes COVID-19, triggers overproduction of interferon-gamma (IFNG), a pro-inflammatory cytokine. IFNG activates indoleamine 2,3-dioxygenase-1 (IDO), enzyme that catalyzes Trp conversion into Kyn, and enzymes of down-stream Kyn pathway that catalyze Kyn conversion into 3-hydroxykynurenine, kynurenic and anthranilic acids in brain and peripheral organs. We reviewed data on SARS-CoV-2 - IFNG – induced changes of peripheral Trp – Kyn pathway, considering their translational potential for personalized psychiatric care. Elevated blood levels of Trp – Kyn pathway metabolites were correlated with the severity of symptoms and predicted the negative outcomes in COVID-19 patients. Association of Trp – Kyn pathway up-regulation with psychiatric complication in non-COVID-19 patients suggests that activation of these pathways contribute to the mechanism(s) of COVID-19 associated psychiatric conditions as well. Increased risk of psychiatric complications in carriers of T (high producer) allele of polymorphic IFNG gene and elevation of serum levels of Kyn and its metabolites in interferon-alpha treated hepatitis C virus patients provides further support for such a suggestion. Assessment of blood levels of Kyn and its metabolites, and polymorphism of Trp – Kyn pathway genes might be developed into personalized biological markers predicting gender/aging dependent individual’s risk of psychiatric complications in COVID-19 patients. Up-regulation of IFNG and IDO is necessary for anti-viral protection. Therefore, inhibition of down-stream Kyn pathway should be considered as a new target for prevention/treatment of COVID-19 and COVID-19-associated psychiatric complications.