Risk factors for COVID-19 are most comorbidities associated with older age, and hypertension is a risk factor for any infectious disease, not just COVID-19.

Phylogenetic analysis of SARS-CoV-2 showed that this virus belongs to line B of the genus betacoronavirus and binds to a similar receptor domain as SARS-CoV. The spike protein (S protein) found in the corona tip of the SARS-CoV2 virus recognizes human ACE-2 with even higher affinity than the original SARS-CoV. ACE-2 has two types of receptors - soluble and membrane-bound receptors.

The key entry gateway for SARS-CoV-2 is the membrane-bound ACE-2 receptor.

First, the S-protein binds to this receptor, followed by the S-protein activation by the serine transmembrane protease TMPRSS2 (a non-specific inhibitor of this protease camostat mesylate is tested against COVID-19 - https://clinicaltrials.gov/ct2/show/NCT04321096). Thus, the S-protein is cleaved by the TMPRSS2 protease into two subunits (S1 and S2), allowing fusion of the viral and cell membranes and the virus's internalization. Unlike SARS-CoV, SARS-Cov2 alters the protein in the ACE-2 receptor binding domain, leading to a much higher binding affinity for ACE-2 than the natural binding partner itself, ACE-2 (by 64 %), and this is also the reason for the significantly higher virulence of sars -cov2 compared to the original sars-cov.

ACE-2 is expressed in human lung tissue, primarily in type II alveolar epithelial cells, which can serve as a viral reservoir. However, ACE-2 is also expressed outside lung tissue, for example, in the heart, kidneys, blood vessels, intestine, which explains the multiorgan failure observed in severe patients with covid-19.

The binding of the virus to ACE-2 leads to depletion of this membrane-bound ACE2 receptor, leading to an increase in AT-II levels (ACE2 cleaves it). An experimental model found that elevated AT-II levels can potentiate lung damage via the ATR1 receptor. One Chinese study found that circulating AT-II levels were markedly elevated in patients with covid and correlated with viral load and lung damage.

Angiotensin 1.7 has a protective effect against lung disease via the MAS1 receptor. Interestingly, angiotensin 1.7, which is formed by the cleavage of AT-II by the enzyme ACE2, was once tested as an antifibrotic in lung diseases of non-oviduous origin. Especially in the absence of the ACE2 enzyme, it can be logically assumed that angiotensin 1.7 will also be missing in the lungs. Not surprisingly, in severe patients with covid-19, acute respiratory syndrome is often due to interstitial fibrotic bilateral pneumonia.

ACEi and sartans increase the expression of ACE-2 receptors, so at first glance, it would seem logical that these drugs could be a significant risk factor. However, it should be noted that it is thought that down-regulation of ACE-2 receptors could be a mechanism in the pathophysiology of ARDS (acute respiratory disease syndrome) and that the virus has been found to reduce the density of ACE-2 receptors in the lung by regulation. Discontinuation of ACEi in a patient who has this drug solely for hypertension has been shown (somewhat unsurprisingly) less at risk than in those who have it due to heart failure or in the secondary prevention of myocardial infarction. Discontinuation of the drug is extremely dangerous here. This is less clear in patients with chronic renal failure.

Take a look at the youtube link below. From about 1.00 minutes later, the participation of RAAS in the pathophysiology of COVID-19 is plotted on the board.