TY - JOUR AU - Cai, Yuping AU - Kim, Daniel J. AU - Takahashi, Takehiro AU - Broadhurst, David I. AU - Yan, Hong AU - Ma, Shuangge AU - Rattray, Nicholas J. W. AU - Casanovas-Massana, Arnau AU - Israelow, Benjamin AU - Klein, Jon AU - Lucas, Carolina AU - Mao, Tianyang AU - Moore, Adam J. AU - Muenker, M. Catherine AU - Oh, Ji Eun AU - Silva, Julio AU - Wong, Patrick AU - Yale IMPACT Research Team AU - Ko, Albert I. AU - Khan, Sajid A. AU - Iwasaki, Akiko AU - Johnson, Caroline H. PY - 2021 DA - July TI - Kynurenic acid may underlie sex-specific immune responses to COVID-19 JO - Science Signaling VL - 14 IS - 690 DO - https://doi.org/10.1126/scisignal.abf8483 AB - Coronavirus disease 2019 (COVID-19) has poorer clinical outcomes in males than in females, and immune responses underlie these sex-related differences. Because immune responses are, in part, regulated by metabolites, we examined the serum metabolomes of COVID-19 patients. In male patients, kynurenic acid (KA) and a high KA–to–kynurenine (K) ratio (KA:K) positively correlated with age and with inflammatory cytokines and chemokines and negatively correlated with T cell responses. Males that clinically deteriorated had a higher KA:K than those that stabilized. KA inhibits glutamate release, and glutamate abundance was lower in patients that clinically deteriorated and correlated with immune responses. Analysis of data from the Genotype-Tissue Expression (GTEx) project revealed that the expression of the gene encoding the enzyme that produces KA, kynurenine aminotransferase, correlated with cytokine abundance and activation of immune responses in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes in COVID-19, suggesting a positive feedback between metabolites and immune responses in males. PB - American Association for the Advancement of Science UR - https://strathprints.strath.ac.uk/77085/ KW - Coronavirus (COVID-19) ER