ACE-2 mediated SARS-CoV-2 entry and comorbidities
Based on recent data, COVID-19 causes mild disease in most infected people. Still, it can progress to a more severe version of respiratory disease accompanied by hyper inflammation, multi-organ failure, and death in patients with immunocompromising and preexisting conditions. This can include conditions such as diabetes, cardiovascular disease, renal, digestive, cancer, COPD and immunodeficiency (Sanyaolu et al., 2020). SARS-CoV-2 is capable of entering human cells by binding to the ACE2 receptor, a carboxypeptidase that usually functions as a counterbalance to the angiotensin-converting enzyme (ACE) of the renin-angiotensin-aldosterone system (RAAS) by converting angiotensin II to angiotensin (1-7) (Figure 2 ). As a result, cells expressing ACE-2 are at a higher risk of establishing infection. SARS-CoV-2 has Open Reading Frames (ORFs) that are responsible for various steps of its disease progression. ORF1ab is responsible for most enzymatic proteins, including S, E, M, and N (Khailany, Safdar & Ozaslan, 2020). The ACE-2 receptor is commonly expressed in the lungs, intestine, kidneys, and heart (Crackower et al., 2002; Donoghue et al., 2000; Hamming, Timens, Bulthuis, Lely, Navis & van Goor, 2004; Tikellis et al., 2003). Recent studies have raised the concern that RAAS blockers such as ACE inhibitors and angiotensin receptor blockers (ARBs) may increase the expression of the ACE-2 receptor, which could potentially increase the susceptibility to SARS-CoV-2 infection in patients taking these medications. Therefore, raising questions about using these vascular medications in COVID-19 patients is crucial, although firm evidence is lacking (Sommerstein, Kochen, Messerli & Grani, 2020; Vaduganathan, Vardeny, Michel, McMurray, Pfeffer & Solomon, 2020). A study also revealed an association between heart disease and COVID-19 in which congestive heart failure was the second most common comorbidity with a 42.9% rate in patients diagnosed with COVID-19, which itself can cause heart injury (Arentz et al., 2020; Lippi et al., 2020). One possibility is that the increased expression of ACE-2 in the heart of COVID-19 patients may aggravate cardiovascular disease compared to healthy people; however, large sample sized studies are warranted to confirm these findings (Paramasivam, Priyadharsini, Raghunandhakumar & Elumalai, 2020). Besides, preexisting conditions in other organs such as the gastrointestinal tract (GIT), kidney, and lungs may influence comorbidities. On the other hand, metabolic dysfunctions in states such as obesity and diabetes are also found to be significant players in comorbidities in COVID-19 (Costa, Rosario, Ribeiro Farias, de Souza, Duarte Gondim & Barroso, 2020; Pugliese, Vitale, Resi & Orsi, 2020; Ritter, Kreis, Louwen & Yuan, 2020).