Figure-1: Active agents on the RAS system
These drugs have an extraordinary therapeutic efficacy, but can also
cause side effects such as hyperkalaemia, hypotension, cough,
angioedema. An increase in ACE-2 concentrations has already been
documented both in murine models and in human patients treated with
ACE-i and ARB. This is because by inhibiting the ACE pathway,
angiotensin I is directed into the conversion pathway to angiotensin
I-7, requiring a higher expression of ACE-2 to compensate for the
greater amount to be converted. The same mechanism is if you use ARB by
blocking the Ang II receptor, in fact the system counter-regulates
increasing ACE and ACE-2, in addition both ACE-i and ARB cause an
increase in the concentration of renin and all the upstream mediators of
the enzyme cascade, and this compensatory mechanism may be favorable or
unfavorable depending on which stage of the SARS-Cov-2 infection the
patient is. With the use of ACE-i or ARB and therefore an increase in
the level of expression of the viral receptor mentioned above, an
increase in infectious power and colonization could plausibly be
obtained. In phase I of the infection, therefore, the virus is
penetrating the cell and is replicating, perhaps in this phase it could
be useful to administer a direct renin inhibitor which, acting upstream,
lowers the concentrations of ACE and especially ACE-2, decreasing the
concentration of receptor protein for the virus. On the contrary, in
phase two or three of the disease, where there is an hyperactive
inflammatory state and where it seems that ACE-2 may have a protective
role in particular on the respiratory tract, it may be appropriate to
increase ACE-2 with ACE-i or blocking the inflammatory effects of Ang II
using ARBs, which also increase the expression of ACE-2 itself. In
recent observational studies the most frequent comorbidities reported in
patients with SARS-Cov-2 are often treated with (ACE-i); however, the
correlation between SARS-Cov-2 and treatment with ACE-i has not been
evaluated and demonstrated in any of the studies. Based on PubMed
research of 28 February 2020, there is no evidence suggested that direct
renin inhibitors cause an increase in ACE2, this drug could therefore be
used to manage the hypertension of patients which are in phase I of the
infection, or in a preventive (non-virus positive patient) way to reduce
the risk of contracting SARS-Cov-2. (14
–15-16-17-18-19-20-21-22-23-24-25-26)
Table 1: Active agents on the RAS system that modulate
the concentration of ACE-2 and hypothetical their use in the various
stages of SARS-Cov-2 infection.