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).