INTRODUCTION
Observational studies [1-3] on patients with novel coronavirus
disease 2019 (COVID-19) tend to favour an association of hypertension
with COVID-19, in which hypertension has been the most frequently
identified comorbidity. Besides, the presence of hypertension tends to
portend a more severe course of COVID-19 [1-3]. Some researchers
were quick to link such association on the use of renin-angiotensin
system (RAS) inhibitors, including angiotensin-converting enzyme
inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), among
hypertensive patients [4]. The issue has since rapidly escalated to
hot debate among the medical community.
The SARS-CoV-2, the causative agent for COVID-19, binds to the ACE2
receptor on host cells to gain entry [5]. In several animal models
and human studies, the expression of ACE2 is increased with the
administration of RAS inhibitors, which suggests a possible increased
susceptibility to SARS-CoV-2 with the use of RAS inhibitors [6-8].
On the other side of the debate, both ACE and angiotensin II, which are
inhibited by RAS inhibitors, seem to function as promoting factors in
lung injury, and thus the suggestion of RAS inhibitors as a potential
therapy for COVID-19. It has been demonstrated that the coronavirus
spike protein binds to ACE2, leading to ACE2 down-regulation, which in
turn results in excessive production of angiotensin II, which causes
vasoconstriction of lung vessels, increased pulmonary vascular
permeability and inflammation, Nonetheless, the lung-protective
mechanism is yet to be firmly established in human trials [9].
Major cardiovascular societies have discredited the association of RAS
inhibitors and the susceptibility to COVID-19 and encouraged to continue
the use of RAS inhibitors in hypertension or other established
indications [10]. Several observational studies have reported on
clinical outcomes among patients with COVID-19 receiving RAS inhibitors
[11-20]. In this regard, we review and analysed the data from these
studies to examine the link of RAS inhibitors with mortality and disease
severity in COVID-19.