Introduction
The recent Coronavirus Disease (COVID-19) pandemic that had emerged
during the last week of December 2019 in Wuhan, China and spread quickly
among 210 countries with more than 2.5 million affected with a mortality
of approximately 3·7% (WHO et al.,2020). COVID-19 is classified in
three segments according to the clinical features; mild, moderate and
severe. The data from around the world suggests that patients with
specific co-morbidities like hypertension, diabetes, COPD,
cardiovascular disease or kidney problems are mostly affected and have
poor clinical outcomes. It can be stated that the patients with multiple
complications are worst affected (Guan et al., 2020).
There is a renewed interest in the Renin-angiotensin system (RAS) amidst
the ongoing pandemic of SARS-CoV2 infections or the Coronavirus
Disease-19 (COVID-19). The novel coronavirus (SARS-CoV2) enters the
human body through interaction of the viral Spike protein with the host
ACE2 receptor, which is associated with down regulation of ACE2. On the
contrary, present data have shown that hypertensive patients treated
with (ACE inhibitors) ACEI/ARB (Angiotensin II receptor blockers) have
elevated expression of ACE2 (Focosi et al., 2020; Ferreario et al.,
2005; Furuhashi et al., 2015). Thus questions arise on whether the use
of ACEI or ARBs in the hypertensive patients or patients with other
comorbidities has any impact in treating COVID-19? or should the
COVID-19 infected individuals continue taking these drugs, because
discontinuation of these drugs may be associated with worsening of the
hypertensive co-morbidity.
RAS has primarily regulatory role in cardiovascular physiology and
pathology (Kuba et al., 2006). Angiotensinogen, the renin substrate, is
hydrolyzed by renin to form decapeptide angiotensin I (ANG I, Figure 1).
Angiotensin-converting enzyme (ACE) is responsible for converting ANG I
to octapeptide angiotensin II (ANG II), which binds to angiotensin II
receptor 1 (AT1R) and causes multiple biological functions such as
vasoconstriction and vascular remodeling. Inhibition of ACE through ACE
blockers results in partial inhibition of the formation of ANG II. ACE2,
a homologue of ACE, hydrolyzes a single amino acid residue from ANG I to
form angiotensin-(1–9) (WHO et al., 2020) and also can convert ANG II
to vasodilator heptapeptide angiotensin-(1–7) through elimination of
single residue phenylalanine. ACE2 and ACE jointly regulates vasodilator
and vasoconstrictor functions to maintain the homeostasis of blood
pressure. Both ACE and ACE2 are mainly found in lung, kidney, heart,
pancreas and blood vessel tissue. Studies have shown that ACE2 protects
from lung injury and reduce the risk of pneumonia (Imai et al., 2005;
Henry et al., 2018).ACE inhibitors (ACEI, such as captopril, lisinopril,
enalapril etc) or AT1R blockers (ARB, such as valsartan, losartan,
telmisartan, olmesartan etc.) exhibits beneficial effect for the
treatment of hypertension.