Association of kynurenine metabolites with cognitive and psychological symptoms in post COVID-19 condition: A...

Cognitive dysfunction and psychological symptoms, including depression and anxiety, are commonly observed in chronic post COVID condition (PCC). Alterations in the kynurenine pathway have been proposed as a potential underlying mechanism; however, their role in neurocognitive and psychological long-term PCC symptoms remains unclear. This study investigates differences in general cognitive function, verbal memory, psychological distress, and peripheral kynurenine metabolites between individuals with PCC and recovered controls and explores group-specific associations.

This study is a subsample of the EPILOC case-control study, assessing PCC (n = 127) and recovered controls (n = 91) ∼75 weeks post-infection. Psychological and neuropsychological measures were consolidated into three components via principal component analysis. Blood samples were analyzed for kynurenine, kynurenic acid, and quinolinic acid. Propensity score matching controlled for confounders. Linear regression models assessed group differences and associations.

PCC exhibited worse general cognitive function and higher severity of psychological distress compared to recovered controls (p_FDR < .001). Across both groups, higher kynurenine levels were associated with better cognitive function (p_FDR = 0.036). The kynurenic acid/kynurenine ratio was negatively associated with general cognitive function in recovered controls (p_bonferroni < .001) but positively in PCC (p_bonferroni < .001). For psychological distress, only the quinolinic acid/kynurenine ratio showed a significant interaction effect: higher values were associated with lower distress in PCC (p_bonferroni < .001), whereas no association was observed in recovered controls. No associations were found for verbal memory.

These findings indicate potentially distinct associations between kynurenine metabolism and cognitive versus psychological outcomes in PCC; however, replication in larger, independent cohorts is required.