Differential methylation as a mediator of COVID-19 susceptibility

The COVID-19 outbreak shows a huge variation in prevalence and mortality on geographical level but also within populations. The ACE2 gene, identified as the SARS-CoV2 receptor, has been shown to facilitate the viral invasion and people with higher ACE2 expression generally are more severely affected. As there is a lot of variability in ACE2 expression between individuals we hypothesized that differential DNA methylation profiles could be (one of) the confounding factors explaining this variability. Here we show that epigenetic profiling of host tissue, especially in the ACE2 promoter region and its homologue ACE1, may be important risk factors for COVID-19. Our results propose that variable methylation can explain (part of) the differential susceptibility, symptom severity and death rate for COVID-19. Our findings are a promising starting point to further evaluate the potential of ACE1/2 methylation and other candidates as a predictor for clinical outcome upon SARS-CoV2 infection.