Genetically determined serum testosterone level and Covid-19 illness level: A mendelian randomization study

Background It is hypothesized that different levels of hormones especially serum testosterone level could explain the sex differences between men and women on the susceptibility and case fatality rate of COVID-19. However, traditional observational studies that support this hypothesis could not effectively establish the causal effects. Objective Utilizing recently published genome-wide associations studies (GWAS) on serum Testosterone level and on COVID-19 related phenotypes, we sought to assess the causality through Mendelian Randomization (MR) analyses. We further applied a suite of statistical genomics methods to further explore the biological mechanisms. Results We found that testosterone level is significantly associated with Covid-19 critical illness. All six MR methods yielded significant associations. There is no significant association between Testosterone and COVID-19 respiratory failure or COVID-19 susceptibility. Conclusion Based on the GWAS currently available, we provide support for a causal role of Testosterone on COVID-19 critical illness.Nevertheless, we recognize that the COVID-19 susceptibility GWAS effort is still ongoing and there is no such strong locus as CCR5 for HIV discovered for COVID-19.