COVID-19 sex difference: X-linked genetic variants affecting disease trajectories and survival.

A striking finding is that more men than women become seriously ill and die of COVID-19. Mouse studies suggest a genetic explanation for this. An obvious hypothesis is that genetic variants on the X chromosome predispose to severe COVID-19 as men have only one X chromosome. Thus, the gene for the ACE2 receptor that Corona virus uses to enter the body's cells is X-linked. The same is true of the genes for two other proteins, AGTR2 and XPNPEP2, that bind to ACE2. Half of the seriously ill COVID-19 patients also have high blood pressure, which is often treated with an ACE inhibitor. In the project, we will with targeted DNA sequencing find the genetic variants in and around these three genes in partly seriously ill Danes with COVID-19, and partly healthy people. We will investigate whether seriously ill women carry one / two high-risk genetic variants, possibly. in combination with skewed X inactivation. With artificial intelligence, the variants found and the clinical data from patients with COVID-19 as well as relevant control groups will be combined with already existing data on disease courses and medication in Danish and Nordic medical registers, and with DNA / genome projects and databases. Knowledge of high-risk genetic variants can determine which individuals have special needs for referral to hospital and prevention via vaccination and targeted treatment when this comes. The project has immediate relevance for the next wave of COVID-19 expected when society normalizes, as well as for new coronavirus outbreaks