# Comparison of Selected Characteristics of SARS-CoV-2, SARS-CoV, and HCoV-NL63
### Morphology, Structure, and Replication of SARS-CoV-2
#### 1.3.5 RAAS Complex  
Severe COVID-19 infection may lead to multi-system organ dysfunction and failure. Multiple case studies demonstrated that underlying hypertension and diabetes mellitus are more common in patients with severe COVID-19 infection than in patients with mild infection. Hypertension has been described as a major risk factor for severe COVID-19 disease. Medications modulating the renin-angiotensin system (RAAS) are used to treat hypertension, therefore concerns about the use of these medications in patients withCOVID-19 infection are reasonable [38]. RAAS inhibitors, angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are commonly prescribed anti-hypertensive drugs. The RAAS is an enzymatic cascade that regulates key physiological processes in the human body and plays a critical role in maintaining blood pressure homeostasis, as well as fluid and salt balance. Angiotensin is a peptide hormone that causes vasoconstriction and blood pressure increase. Angiotensin is cleaved at the N-terminus by renin to result in angiotensin I, which will later be modified to become angiotensin II. ACE2 is integral membrane-bound monocarboxylopeptidase protein that serves as a counter regulatory role in cardiovascular homeostasis. ACE2 converts Angiotensin II to Angiotensin (1-7) thereby creating a cytoprotective environment through anti-inflammatory, anti-fibrotic, anti-proliferative, and vasodilatory effects via MAS receptor. The classical RAAS axis, formed by ACE, angiotensin II, and angiotensin receptor type 1 (AT1), activates several cell functions and molecular signalling pathways related to tissue injury and inflammation. SARS-CoV-2 enters lung cells via the ACE2 receptor [38; 39]. Therapy in patients with COVID-19 has raised concerns about the use of RAAS inhibitors, which may affect the occurrence of ACE2 on the cell membrane. It may also impact increased ACE2 expression following therapy in blocking ACE inhibitors [26]. Physicians have questioned whether this may affect the virulence of SARS-CoV-2. The use of angiotensin receptor blockers (ARBs) losartan, candesartan, and valsartan is common worldwide. Patient data are too limited to support or refute these assumptions. However, the effects of RAAS blockers on ACE2 levels suggest that the omission of ACE2 blockers may be detrimental rather than beneficial in patients with lung injury [40]. The ACE2 reduces angiotensin II effects on vasoconstriction, sodium retention, and fibrosis. [41]. Circulating levels of soluble ACE2 are low and ACE2 function in the lung is relatively minimal under normal conditions, however may be increased in some clinical cases. The effect of RAAS inhibitors on ACE2 in humans is unknown due to the fact that ACE inhibitors and ARBs have different reactions on angiotensin II, the primary substrate of ACE2 [34]. The effects of these substances on ACE2 levels and their activity may therefore vary. Despite considerable structural homology between ACE and ACE2, their active enzyme sites are different. As a result, ACE inhibitors do not directly affect ACE2 activity in clinical practice. Experimental animal models have shown mixed findings related to the results of ACE inhibitors on ACE2 levels or tissue activity. Similarly, animal models have produced inconsistent findings related to outcomes of ARBs on ACE2, with some indicating that ARB may increase messenger RNA expression. In post-mortem autopsy, heart tissues from several patients who succumbed to SARS-CoV and heart samples had detectable viral SARS-CoV genome. These patients were also characterized by reduced myocardial ACE2 expression, which further confirmed that ACE2 expression was decrease after virus infection. From the recent information, it has been found that RNA sequencing has revealed an abundance of ACE2 expression in the ileum, heart, kidney, bladder, airways, lung, esophagus, stomach, and liver. Current studies have shown that both ACE inhibitors and ARB affect the mRNA expression of ACE2.