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).