Insights from immunomics and metabolomics on the associations between prostatic diseases and coronavirus disease 2019

The causal associations and potential mechanisms between prostatic diseases, the predominant male urological disorders, and the course of COVID-19 remain unclear.

A 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.

Genetically 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%.

Our 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.