Potential causal role of mitochondrial biological effects in COVID-19: Evidence from Mendelian randomization study

Potential mitochondrial biomarkers play an important role in probing COVID-19 physiopathology. We aimed to investigate the causal effects of 82 mitochondrial biomarkers on COVID-19 in a population-based public database. Based on the IEU Open genome-wide association studies database and the genome-wide association studies Catalog database, the significant single-nucleotide polymorphisms of mitochondrial and COVID-19 were extracted as instrumental variables. The inverse variance weighting (IVW) method and the Bayesian weighting method in the two-sample Mendelian randomization (MR) method were used for the main causal analysis. Sensitivity tests were performed using the MR-Egger regression test, the MR-PRESSO test for multiple residuals and outliers, the Cochran Q statistic, and the leave-one-out method, and directionality tests were performed using the MR-Steiger method. The protective factors of COVID-19 were determined by IVW method and Bayesian weighting method: Apoptosis-inducing factor 1, mitochondrial (PIVW = 9.6 × 10-5; PBWMR = 4.2 × 10-2) and risk factors: 39S ribosomal protein L33, mitochondrial (PIVW = 2.8 × 10-3; PBWMR = 1.9 × 10-3) and 39S ribosomal protein L52, mitochondrial (PIVW = 2.0 × 10-2; PBWMR = 7.3 × 10-3) and Mitochondrial ubiquitin ligase activator of NF-κB-1 (PIVW = 2.7 × 10-2; PBWMR = 4.8 × 10-2). In the sensitivity test, we did not find heterogeneity, pleiotropic and reverse causality. In this study, we identified 4 potential biomarkers of mitochondrial dysfunction associated with COVID-19, providing new insights into the realization of COVID-19 precision medicine and potential mechanisms.