ACE2 is not only prevalent in the pathogenesis of COVID-19, but is part of RAS signaling. Though data is scarce on the topic, it is known now that ACE2 is both targeted by SARS-CoV-2 in its entrances to cells and a critical player in anti-inflammation during RAS signaling—converting angiotensin II to angiotensin 1-7.
The age-associated decrease of ACE2 expression, which investigators have observed in the lungs of rats, is in line with “a constellation of major proinflammatory changes perpetrated by an age-associated increase in RAS signaling throughout the body,” the team wrote.Similarly, in the COVID-19 pandemic, it is plausible that greater expression of ACE2 leads to higher predisposition to incur the disease,” they wrote.
Hence, compared with young individuals, older persons with (cardiovascular disease) who already have reduced ACE2 levels will be expected to be more predisposed to exaggerated inflammation with further reduction in ACE2 expression in the context of COVID-19, manifesting with greater disease severity,” they explained.Such proinflammatory profiles are featured in patients with hypertension and diabetes—a pair of diseases highly common in older patients.
The increase of ACE2 in such patients with ACE inhibitors and angiotensin receptor blockers (ARBs) presents a paradox to investigators: how can ACE2 reduction in older, cardiovascular-risk patients put them at greater risk of COVID-19 severe symptoms when ACE2 is the gateway for the disease into cells?
I don't think the reduction of ACE2 expression has any effect, if an epithelial cell is expressing a single ACE2 then it is vulnerable and if a single virus comes into contact it will bind to it and begin fusing with the cell membrane. The scale of the reduction is a critical metric, if lung cells are known to have a very high level of ACE2 expression then even a reduction of 50%, which I would intuit is orders of magnitude greater than the actual reduction, it is still a target-rich environment with many sites of potential infection on each cell. Even if it was an absurd reduction, say half of previous cells express zero ACE2 proteins, you would still have half of the cells vulnerable to infection which is more than enough to collapse the system if compromised.
Furthermore, from my understanding, the major issue is the inflammation and serum secretions essentially drowning the alveolar sacs, preventing their ability to perform the vital gas exchange functionality. If the level of vulnerability is virtually unaffected by the reduction of expression, then the efficiency of the immune system becomes the crucial mediator as a prolonged infection results in greater inflammation and therefore more detrimental interference in the ability to absorb oxygen.
Hi dr, the treatment with ACE inhibitors can reduced this hazards in patients.
https://www.researchgate.net/publication/340261837_Treatment_with_ACE-inhibitors_is_associated_with_less_severe_SARS-Covid-19_infection_in_a_multi-site_UK_acute_Hospital_Trust
Totally agree with Vincent Paul Schmitz
Also I read a paper suggesting that targeting ACE2 could lead to some serious disturbance in Renin - Angiotensin system. Besides, transcriptome of cell lines infected with SARS CoV-2 doesn't seem to be affected much by ACE2 transduction.
What must be said is the the SARS-CoV-2 can infect cells through multiple receptors. ACE2 is just one of those receptors. Furthermore, in a single individual, multiple factors contribute to severity of infection, not just the expression of ACE2.
Though decreased ACE2 expression in cells has been consistently shown in the elderly people, certain level of decrease due to senescence may not have substantial effects on physiological functions (subject to research). The main important thing about the decrease in ACE2 expression and infection severity is that ACE2 itself is protective under normal conditions. Increased ACE2 expression has been demonstrated to attenuate inflammation and vascular endothelial impairment. Consequently, decreased expression of ACE2 will predispose to inflammatory state. This will mean that elderly people already have elevated levels of proinflammatory mediators than younger people. If we consider the fact that certain level of ACE2 decrease may not substantially affect the rate of SARS-CoV-2 invasion (the virus also uses other receptors to gain access into the host cells), then, elderly people will be more prone to SARS-CoV-2 infection. Notably, senescence-induced structural and physiological changes, including decreased ACE2 expression, seem to play a critical role.
Menizibeya Osain Welcome - Both SARS-CoV and MERS-CoV have demonstrated antibody-dependent enhancement (ADE) if the antigenic determinant is confined to the receptor-binding domain (RBD) of a single subdomain of the spike protein homo-trimer. Proteolytic cleavage of the two unbound spike protein subdomains undergo a conformational change, preferentially binding to and initiating the viral capsid fusion to the cell membrane of CD32A+ immuno-associated; instead of ACE2.
In this preprint I wrote some considerations about COVID-19 and childhood asthma trying to explain the differences between adults and children. ACE2 decrease may not be the only cause that exposes elder people at greater risk. Also a pre-existing condition of inflammation that occurs with age can play an important role, particularly by increasing of IL-6.
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Preprint Potential detrimental role of soluble ACE2 in severe COVID-1...