Kynurenic acid underlies sex-specific immune responses to COVID-19

Sex-related differences in Coronavirus Disease (COVID-19) severity and mortality exist, with the male sex being a potential risk factor1. It was recently shown that patients with mild to moderate SARS-CoV-2 infection have elevated levels of inflammatory cytokines and chemokines, and sex-differences in these immune responses. In this study, we used an untargeted metabolomics workflow with multivariable logistic regression to identify metabolites that were associated with COVID-19 disease. Serum samples were analyzed from COVID-19 patients (n=22 women and n=17 men), and healthcare worker (HCW) controls that had no evidence of COVID-19 disease (n=10 women and n=10 men). We further investigated the sex differences in the associations between metabolites and immune markers, and found that the relevance of kynurenic acid, KYAT and AhR activation in COVID-19 could be of utmost importance.