Fig. 3.

Hypothetical scheme for the interaction of the CORONA virus and angiotensin converting enzyme-2 (ACE2). The CORONA virus binding with its spike protein to ACE2, which is processed by the proteinase ADAM17 leading to the internalization of the CORONA virus and ACE2 into the cell where the viral genome is released. The internalization as well as the shedding of ACE2 from the cell surface and its release into the circulation reduces membrane-bound ACE2. Furthermore, ACE2 is reduced by pathological conditions like pulmonary fibrosis, asthma, COPD, pulmonary hypertension, smoking and old age [17]. On the contrary, membrane-bound ACE2-concentrations are higher following treatment with ACE-inhibitors, AT1-blockers and potentially ibuprofen, and ACE2 is more abundantly expressed in childhood and at young age. As ACE2 forms more Ang 1–7 from angiotension-II to stimulate the MAS-receptor mediating anti-proliferative, anti-inflammatory action, hypothetically enhanced ACE2-expression might cause more infection by acting as a receptor for viral cell entry and protect from pulmonary complications. In conditions where is downregulation of ACE2, less infection might occur, but severity of COVID-19-related ARDS can be more severe. This hypothesis fits with the higher likelihood of pulmonary complications in certain disease conditions and in aging. Notably, these data are derived from experimental and observational data, but not from controlled clinical studies and need to be scrutinized in clinical conditions