Insights from Immunomics and Metabolomics on the Associations between Prostatic Diseases and COVID-19

Abstract

BackgroundThe causal associations and potential mechanisms between prostatic diseases, the predominant male urological disorders, and the course of COVID-19 remain unclear. MethodsA two-sample Mendelian randomization (MR) analysis was performed to evaluate causal associations between prostate cancer, benign prostatic hyperplasia, and prostatitis and different COVID-19 outcomes (SARS-CoV-2 infection, hospitalized COVID-19, and severe COVID-19). Reverse MR, linkage disequilibrium score regression, and Bayesian colocalization analyses were subsequently performed to strengthen the identified causal relationships. Furthermore, immunome- and metabolome-wide MR analysis was conducted to prioritize COVID-19-associated immune characteristics and metabolites. Two-step MR analysis was performed to evaluate the mediating effects of the immunome and metabolome on the associations between prostatic diseases and COVID-19. ResultsGenetically predicted prostatic diseases were not causally associated with severe COVID-19, while prostatitis was suggested to be an independent risk factor for SARS-CoV-2 infection (odds ratio (OR) =1.11, 95% confidence interval (CI) 1.01 to 1.23; P = 0.03). Multiple sensitivity tests verified the reliability of the established causal relationships. Dozens of blood immune and metabolic features were identified to reveal the immune and metabolic profiles of different COVID-19 courses. Moreover, PDL-1 on monocyte was found to mediate the interaction between prostatitis and SARS-CoV-2 infection, with a mediation proportion of 9.2%. ConclusionOur study identified the causal relationships of prostatic diseases with COVID-19 and suggested pathways explaining these associations through alterations in the blood immunome and metabolome.