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.