Dear Editor,
SARS-CoV-2 (COVID-19) is responsible for the current global pandemic. At
the date, no antivirals directed against the virus or effective vaccines
are available. (1) It is essential to recognise the risk factors and
components that may play a protective role. There is no clear evidence
on the correlation between changes in the Renin-angiotensin system (RAS)
by ACE-is, ARB or DRis and COVID-19 infection.(2) (3) (4) Randomised
controlled trials are needed to verify the involvement of COVID-19 viral
infection and chronic treatment with these drugs. A possible scientific
hypothesis to investigate is the role of the neprilisin inhibitor
Sacubitril in association with valsartan in the more severe stages of
COVID-19 infection. The challenge to defeat the current pandemic poses
several objectives, among them try to give added values to therapeutic
solutions, in this direction the association sacubitril/valsartan has
already demonstrated the therapeutic efficacy in the treatment of
chronic symptomatic heart failure with reduced ejection fraction in
several studies (5), indirectly the therapeutic benefits of
cardiovascular type are also directed to a decrease in the risk of
infection and complications from COVID-19. Furthermore, there is
evidence of a significant increase in NT-proBNP in COVID-19 patients.
(6) Studies show that higher NT-proBNP was an independent risk factor
for death in patients with severe COVID-19, (7) moreover, NT-proBNP is
associated with proinflammatory effects. (8) (9) Sacubitril through its
mechanism of action increases neprylisin-degraded peptides, such as
natriuretic peptides (NP), ANP and BNP, (10) evidence associates these
peptides with anti antiflammatory, antihypertrophic and antifibrotic
effects, recent evidence shows that IL-1𝛽 secretion is strongly
inhibited by the BNP/NPR-1/cGMP axis to all molecular mechanisms closely
controlling its production and release, NF-kB, ERK 1/2, and all elements
of the NALP3/ASC/Caspase-1 inflammasomic cascade, and that NALP3
inflammatory inhibition is directly related to the deregulatory effect
of BNP on the activation of NF-kB/ERK ½,(11) also the decrease of
NT-proBNP by Sacubitril is known. Valsartan in association, by blocking
the AT-1r receptor of ang II, decreases profibrotic and proinflammatory
activity mediated by AT-1r, and indirectly increases the action of ang
II on AT-2r with antifibrotic, antifibrotic effects. Based on the
evidence and in relation to our generated hypothesis, we believe that a
use of sacubitril/valsartan in the most severe stages of COVID-19
infection could have therapeutic efficacy, with anti-inflammatory and
antifibrotic effects mediated by natriuretic peptides. Clinical studies
are required to confirm this hypothesis.