The ACE-2 in COVID-19: Foe or Friend?

Abstract

COVID-19 is a rapidly spreading outbreak globally. Emerging evidence demonstrates that older individuals and people with underlying metabolic conditions of diabetes mellitus, hypertension, and hyperlipidemia are at higher risk of morbidity and mortality. The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT1R axis and ACE-2-Ang-(1–7)-Mas axis. In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT1R axis with a downregulation of ACE-2-Ang-(1–7)-Mas axis. The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. On the other hand, the ACE-2-Ang-(1–7)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. In effect, the balance between these two axes may determine the prognosis. The already strained ACE-2-Ang-(1–7)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19.

The Perfect Storm: COVID-19 Health Disparities in US Blacks

“…ACE2 is essential for metabolic control of respiratory, vascular, myocardial, kidney, and pancreatic functioning among others [ 44 – 46 ]. In metabolic disorders for example, it is known that there is an upregulation of ACE2 that interacts with the angiotensin II type 1 receptor (AT1R) which in doing so has pathologic pro-inflammatory and pro-fibrotic effects [ 47 , 48 ]. Robust replication of the entered SARS-CoV-2 through ACE2 receptors triggers release of large numbers of cytokines, especially IL-6, causing acute fatal “cytokine storms”; that is, efficient entry followed by replication of the virus is essential for SARS-CoV-2 pathobiology.…”

Cannabis compounds have anti-inflammatory activity in lung epithelial cells but pro-inflammatory activity in macrophages while increasing phagocytosis in vitro

“…In cells of patients with severe symptoms of COVID-19, ACE2 was substantially upregulated 199 fold; this upregulation was suggested to be one of the factors leading to disruption of the renin-angiotensin system 22 . The ability of F CBD to reduce ACE2 expression is important concerning treatment of COVID-19 patients, yet should be considered with care as the advantages and disadvantages of ACE2 expression reduction are disputed 20 .…”

Is There a Role for Environmental and Metabolic Factors Predisposing to Severe COVID-19?

“…In all these countries, there are similar elderly populations with no major demographic differences. The same is true for the rate and distribution of comorbidities that had been defined as risk factors for severe COVID-19 disease such as diabetes, hypertension or heart disease [8][9][10][11]. There is currently no clear evidence for major differences in genetic predisposition between the populations of these Western countries.…”