Figure 1 : Sacubitril/Valsartan mechanism of action and biological effects
The beneficial effects of NEPi are attributable to decreased degradation of natriuretic peptides. Natriuretic peptides cause vasodilation by stimulating the guanylate cyclase receptor to produce cGMP. In addition, sacubitril administration is known to decrease NT-proBNP, which in severe cases COVID-19 is increased. In patients with COVID-19, with and without symptoms attributable to pneumonia, there is evidence of a significant increase in NT-proBNP, regardless of left ventricular dysfunction. Indeed, studies show that NT-proBNP levels are also the results of acute renal lesions and pro-inflammatory molecules such as interleukin-1 and C-reactive protein,(72) In addition, natriuretic peptides act to suppress the renin-angiotensin and sympathetic systems and decrease endothelin secretion. In addition, as mentioned above, natriuretic peptides also exert anti-inflammatory, antifibrotic and antihypertrophic effects. In particular, some evidence shows direct mediated anti-inflammatory effects. In particular, some studies associate the BNP peptide with an important inhibitory effect on the activation of inflammatory NALP3, which is related to the reduction of BNP-induced NF-kB and ERK1/2 activation. In addition, for this class of drugs acting on RAS, there is potential indirect protection against SARS-CoV-2. In fact, patients with cardiovascular disease are at high risk of pneumonia, studies show that the use of drugs that block RAS decreases this risk. (73)(74) On the basis of the evidence described and in relation to the hypotheses suggested by us, the use of the sacubityl/valsartan association in patients with COVID-19, especially in severe cases, could be of therapeutic benefit, with cardioprotective, anti-inflammatory and antifibrotic effects capable of fighting lung damage, through an increase in the natriuretic peptide system and a decrease in the effects of AT-1 receptor-mediated Ang-II. Well-structured clinical studies are required to confirm these hypotheses.