**16. Soluble human (ACE2)**

For successful COVID-19 treatment, it has been proposed that blocking the interaction between the viral spike protein and ACE2, which is the host receptor for SARS-CoV-2 infection, might be a viable treatment [105].

This finding has opened debate about whether ACE inhibitors and/or angiotensin receptor blockers could be used to treat COVID-19 or, conversely, aggravate the disease [106]. ACE inhibitors can cause a decrease in angiotensin I levels, triggering a possible negative feedback loop, which in turn activates more ACE2 receptors to interact with available angiotensin I substrates. On the contrary, angiotensin receptor blockers may theoretically provide clinical benefit by blocking the ACE2 receptor. There are inconsistent *in vitro* results to verify if these drugs are harmful or protective in patients with COVID-19. There is insufficient data to conclude that patients on long-term ACE inhibitors, or ARB medication are at a higher risk of poor COVID-19 outcomes [107].

A recent *in vitro* investigation found that humanized recombinant soluble ACE2 (hrsACE2) may inhibit SARS-CoV-2 replication, resulting in significantly lower virus load in vero cell lines in a dose-dependent manner [108]. These findings are encouraging because they offer up a new avenue for using hrsACE2 to prevent SARS-CoV-2 infection at an early stage by inhibiting the virus's entrance into target cells, potentially saving patients from lung damage.
