However, the low expression of ACE-2 on the cell surface could also be interpreted as a viral defense mechanism. In the past, the down regulation of ACE-2 had been correlated with faster cell-cell spread of human coronaviruses [51] and with more severe clinical manifestations [52,53]. Guzzi et al., in a recent study, hypothesized that even for COVID-19 the down regulation of ACE-2 could be a mechanism induced by SARS-CoV-2 to obtain a faster intercellular diffusion [54]. Studies carried out to understand the effect of angiotensin receptor blocker (ARB) drugs in patients with COVID-19, have suggested mechanisms through which the upregulation of ACE-2 may be protective during SARS-CoV-2 infection [55]. ARBs, in fact, greatly increase the cellular expression of ACE-2 [56]. However, since SARS-CoV-2-ACE-2 interaction represents the first step of a chain of events, if the upregulation of ACE-2 is not followed by the increase of certain cell proteases essential for internalization and viral activation, it would only result in the sequestration of SARS-CoV-2 on the cell membrane limiting viral infection [35]. Furthermore, the metalloproteinase ADAM17 can act upon the membrane-bound ACE-2, leading to the release of a soluble form of ACE-2. If the increased expression of ACE-2 correlates with an increase in soluble ACE-2, this might act as a decoy receptor for SARS-CoV-2 by limiting viral entry into target cells [35].