Renin aldosterone-angiotensin system (RAAS), ACE 2 and COVID-19
RAAS plays a pivotal role in the liver, heart, lungs, kidney and reported to be dysregulated in hypertension, diabetes, chronic kidney diseases and other cardiovascular diseases (Petrie, Guzik & Touyz, 2018). RAAS alteration increases the production of Angiotensin II (Ang II), which induces vasoconstriction, inflammation, oxidative stress, hypertrophy and to counteract this there is a compensatory increase in the expression of 2 (Nehme, Zouein, Zayeri & Zibara, 2019; Singh, Gupta & Misra, 2020). As explained, SARS-CoV-2 enters the host cell through lung epithelial 2 receptor at low cytosolic pH which causes ARDS, lung infection and hypoxia in turn induces a massive release of cytokines, increases oxidative stress, alters myocardial oxygen demand-supply leading to myocardial injury (Cure & Cumhur Cure, 2020). Further, due to extensive lung injury by SARS-CoV-2, it may release into the blood circulation and invaded the other cells, tissue or organs where 2 is abundantly present (Heart, Kidney, Liver, Pancreas, Brain and fetus) which might provide a possible route for the entry of the SARS-CoV-2 and may induce septic shock and multi-organ failure with cytokine storms (Bornstein et al., 2020; Wang et al., 2020b).
A widely used drugs like angiotensin-converting enzyme inhibitors, angiotensin 1 receptor blockers, non-steroidal anti-inflammatory drugs and thiazolidinediones up-regulate the 2 expression thereby it may facilitate the virus transmission in kidney, heart, aorta, pancreas and liver, which might be responsible for increased co-morbidity and mortality (Leung et al., 2020; Singh, Gupta & Misra, 2020). Hence, the usage of these drugs needs to be carefully monitored among COVID-19 patients suffering from high blood pressure, other cardiovascular diseases, nephropathy and inflammatory disorders. Further, smoking may be another reason for increased mortality in the COVID-19 patients; smokers are more prone to viral respiratory tract infections as chronic exposure of cigarette smoke causes destruction of immune cells, activation of airway macrophages, increases inflammation and oxidative stress in the lungs (Feldman & Anderson, 2013). In addition, evidence reveals that smoking upregulates the ACE 2 expression in airway epithelium, alveolar macrophages and type 2 pneumocytes where the primary viral replication occurs and making patients prone to COVID-19 disease. Similarly, ACE 2 is found to be upregulated in chronic obstructive pulmonary disorder (COPD) patients, which further can amplify the SARS-CoV-2 infection and responsible for increased co-morbidity (Brake, Barnsley, Lu, McAlinden, Eapen & Sohal, 2020; Cai, Bossé, Xiao, Kheradmand & Amos, 2020). Hence, the ACE 2 upregulation by drugs, chronic smoking and COPD patients might be at higher risk of COVID-19 and may increase the mortality. Conversely, SARS-CoV-2 downregulates the lung 2 to produce a toxic level of Ang II that accumulates in the lungs which induces inflammation, fibrosis, increases oxidative stress, hypoxia and ultimately respiratory failure (Hanff, Harhay, Brown, Cohen & Mohareb, 2020).