Subsequently, an exacerbated decrease in the membrane-bound active ACE2 form, both for ADAM17 and TMPRSS2 over-activation, and for the infection itself, may exacerbate the RAS imbalance (ACE/ACE2) in patients with specific comorbidities, such as cardiovascular disease, hypertension, diabetes and chronic lung disease. Here, TMPRSS2 is linked to infection.