Neprilysin inhibitor-angiotensin II receptor blocker combination (sacubitril/valsartan): rationale for adoption in SARS-CoV-2 patients.

Abstract

On 11 March 2020, the World Health Organization (WHO) declared the coronavirus disease 2019 (COVID-19) outbreak as a ‘pandemic’. No valid therapy for COVID-19 is actually available. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is empirically treated with antivirals, antimalarics, tocilizumab, etc. Production of a vaccine for COVID-19 has been attempted, although approval needs time. We describe a possible, alternative approach for treating COVID-19. Lymphocyte count has been associated with increased disease severity risk. Patients who died from COVID-19 showed a significantly lower lymphocyte count than survivors, therefore this should be closely monitored. Repletion of lymphocytes could probably have beneficial effects on recovery. A recent hypothesis suggests that the inhibition of the angiotensin 1 receptor (AT1R) may provide benefits to COVID-19 patients. This hypothesis is based on the observation that the SARS-CoV-2 virus uses angiotensin-converting enzyme 2 (ACE2) as a receptor to bind the virus to the bronchial cell membrane. The enzymes ACE and ACE2 belong to the same peptidase family but have two very different physiological functions. ACE cleaves angiotensin I to generate angiotensin II (Ang II), which binds to and activates AT1R, and thus promoting vasoconstriction. ACE2 cleaves Ang II and generates angiotensin 1-7, a powerful vasodilator acting through Mas receptors. AT1R antagonists are widely used in hypertensive patients but they increase the ACE2 cardiac expression in rats and the urinary concentration of ACE2. It has been demonstrated that the binding of virus to ACE2 leads to ACE2 down-regulation,