Dataset Information

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

ABSTRACT: Coronavirus disease-2019 (COVID-19) has poorer clinical outcomes in males compared to females, and immune responses underlie these sex-related differences in disease trajectory. As immune responses are in part regulated by metabolites, we examined whether the serum metabolome has sex-specificity for immune responses in COVID-19. In males with COVID- 19, kynurenic acid (KA) and a high KA to kynurenine (K) ratio was positively correlated with age, inflammatory cytokines, and chemokines and was negatively correlated with T cell responses, revealing that KA production is linked to immune responses in males. Males that clinically deteriorated had a higher KA:K ratio than those that stabilized. In females with COVID-19, this ratio positively correlated with T cell responses and did not correlate with age or clinical severity. KA is known to inhibit glutamate release, and we observed that serum glutamate is lower in patients that deteriorate from COVID-19 compared to those that stabilize, and correlates with immune responses. Analysis of Genotype-Tissue Expression (GTEx) data revealed that expression of kynurenine aminotransferase, which regulates KA production, correlates most strongly with cytokine levels and aryl hydrocarbon receptor activation in older males. This study reveals that KA has a sex-specific link to immune responses and clinical outcomes, in COVID-19 infection.

SUBMITTER: Cai Y

PROVIDER: S-EPMC7491534 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:IntroductionThe key to understanding the COVID-19 correlates of protection is assessing vaccine-induced immunity in different demographic groups. Young people are at a lower risk of COVID-19 mortality, females are at a lower risk than males, and females often generate stronger immune responses to vaccination.MethodsWe studied immune responses to two doses of BNT162b2 Pfizer COVID-19 vaccine in an adolescent cohort (n = 34, ages 12-16), an age group previously shown to elicit significantly greater immune responses to the same vaccine than young adults. Adolescents were studied with the aim of comparing their response to BNT162b2 to that of adults; and to assess the impacts of other factors such as sex, ongoing SARS-CoV-2 infection in schools, and prior exposure to endemic coronaviruses that circulate at high levels in young people. At the same time, we were able to evaluate immune responses to the co-administered live attenuated influenza vaccine. Blood samples from 34 adolescents taken before and after vaccination with COVID-19 and influenza vaccines were assayed for SARS-CoV-2-specific IgG and neutralising antibodies and cellular immunity specific for SARS-CoV-2 and endemic betacoronaviruses. The IgG targeting influenza lineages contained in the influenza vaccine were also assessed.ResultsRobust neutralising responses were identified in previously infected adolescents after one dose, and two doses were required in infection-naïve adolescents. As previously demonstrated, total IgG responses to SARS-CoV-2 Spike were significantly higher among vaccinated adolescents than among adults (aged 32-52) who received the BNT162b2 vaccine (comparing infection-naïve, 49,696 vs. 33,339; p = 0.03; comparing SARS-CoV-2 previously infected, 743,691 vs. 269,985; p <0.0001) by the MSD v-plex assay. There was no evidence of a stronger vaccine-induced immunity in females compared than in males.DiscussionThese findings may result from the introduction of novel mRNA vaccination platforms, generating patterns of immunity divergent from established trends and providing new insights into what might be protective following COVID-19 vaccination.

Dataset Information

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets