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 populations¹. TheACE2gene, identified as the SARS-CoV2 receptor, has been shown to facilitate the viral invasion and people with higherACE2expression generally are more severely affected^{2, 3}. As there is a lot of variability inACE2expression 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 theACE2promoter region and its homologueACE1, 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 ofACE1/2methylation and other candidates as a predictor for clinical outcome upon SARS-CoV2 infection.