Role of ACE 2 and Vitamin D: The Two Players in Global Fight against COVID-19 Pandemic

Abstract The global pandemic of coronavirus disease 2019 (COVID-19) has spread across the borders, gaining attention from both health care professional and researchers to understand the mode of entry and actions induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), its causative agent in the human body. The role of angiotensin-converting enzyme–2 (ACE2) in facilitating the entry of the virus in the host cell by binding to it is similar to SARS-CoV-1, the causative agent for severe acute respiratory syndrome (SARS) which emerged in 2003. Besides the role of ACE2 as a molecular target for the virus, the review displays the potential benefits of ACE2 enzyme and various agents that modify its activity in curbing the effects of the deadly virus, thus unfolding a dual character of ACE2 in the current pandemic. As evident by the differences in the susceptibility toward viral infection in children and geriatric population, it must be noted that the older population has limited ACE2 levels and greater infection risk, whereas the situation is reversed in the case of the pediatric population, demonstrating the defensive character of ACE2 in the latter, despite acting as receptor target for SARS-CoV-2. Also, the upregulation of ACE2 levels by estrogen has indicated greater resistance to infection in females than in the male human population. ACE2 is a carboxypeptidase, which degrades angiotensin II and counteracts its actions to protect against cardiovascular risks associated with the virus. Another contribution of this enzyme is supported by the role of circulating soluble ACE2, which acts as a receptor to bind the virus but does not mediate its actions, therefore blocking its interaction to membrane-bound ACE2 receptors. The review also shares the enhanced risks of developing COVID-19 infection by using ACE inhibitors and ARBs. However, both these agents have been reported to upregulate ACE2 levels; yet, adequate evidence regarding their role is quite inconsistent in human studies. Furthermore, the role of vitamin D has been highlighted in regulating the immune system of the body through renin-angiotensin-aldosterone system (RAAS) inhibition, by downregulating host cell receptor expression to prevent virus attachment. Besides, vitamin D also acts through several other mechanisms like upregulating antimicrobial peptides, fighting against the proinflammatory milieu created by the invading virus, and interfering with the viral replication cycle as well as calcitriol-mediated blockage of CREB protein. Hypovitaminosis D is attributed to elevated risks of acute respiratory distress syndrome (ARDS), lung damage, and cardiovascular disorders, further increasing the severity of COVID-19 infection.