The Angiotensin Converting Enzyme 2 (ACE-2) has been at the center of uncovering the pathogenesis of Covid-19. ACE-2 decreases the production of angiotensin II in the body. Angiotensin II is a vasoconstrictor, and logically angiotensin receptor blockers are a commonly used anti-hypertensive medication.
In addition to being pro-hypertensive, angiotensin II induces many immune responses in the body, and it has also been linked to inflammatory lung injuries. Therefore the decrease of angiotensin II by ACE-2 serves as a protective mechanism.
It is now known that Covid-19 binds to ACE-2 in the lungs, with its spike proteins. This causes the overproduction of angiotensin II, leading to over-activation of immune cells.
Furthermore, it has been found that ACE-2 is expressed by AT2 cells. AT2 cells in the lungs produce surfactant, maintaining the elasticity of the lungs, and producing other cell types that are responsible for gas exchange in the lungs (AT1 cells). So its hypothesized that the depletion of ACE-2 by Covid-19 can lead to fibrosis of the lungs, through the depletion of AT2 and AT1 cells.
Links to at-risk populations
Younger patients who have contracted Covid-19 are seen to have mild or no symptoms at all. Younger patients are seen to have higher levels of ACE-2 and higher regenerative capacity within their lungs, aiding in the clearance of the viral load. Older patients with comorbities such as hypertension and diabetes show a decreased immune response and regenerative capacity in their lungs – therefore leading to lung inflammation following infection with Covid-19.
A link can also be made between air pollution and ACE-2. It has been shown that ACE-2 plays a critical role in tissue remodeling following injury from particulates in the air. Decrease in ACE-2 levels can critically hinder this process. New York, Northern Italy, Wuhan, and Tehran are known areas with high air pollution, also among the heaviest hit with Covid-19.