Our observation that individuals suffering from co-morbidities recognised to be associated with severe COVID-19 may have lower pre-infection ACE2 levels in some tissues may support a theory that pre-existing low ACE2 levels in at risk-individuals are then reduced further upon SARS-CoV-2 infection, contributing to the dysregulation of the RAS characteristic of severe COVID-19 [60]. Here, ACE2 is linked to infection.