The novel coronavirus disease 2019 (COVID-19) has rapidly spread around the world since it was first reported in December 2019 within Wuhan, China as a pneumonia of unknown etiology . Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), termed by the World Health Organization (WHO), represents the third large-scale epidemic related to coronaviruses . Although the disease was first reported within China, a retrospective study has subsequently found evidence that SARS-CoV-2 was spreading within France four days before it was reported in Wuhan, China and one month before the first official case in the country . Since its initial discovery, SARS-CoV-2 has spread worldwide, infecting over 6.0 million people and led to the death of more than 350,000 people . The severity of the disease widely ranges from an asymptomatic disease-state to patients exhibiting acute respiratory distress syndrome (ARDS), necessitating critical medical intervention to attempt to prevent patient death . It was subsequently discovered that Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the SARS-CoV-2 spike (S-) protein, allowing the virus to enter cells . ACE2 is a potent negative regulator of the renin angiotensin system (RAS), which is critical for maintaining the homeostasis of RAS.
The ACE2 gene is composed of 805 amino acids and is a type I integral membrane glycoprotein. ACE2 degrades angiotensin (Ang)-II, a potent vasoconstrictor (that is also pro-inflammatory and promotes fibrosis), and converts it into Ang (1-7) . Ang (1-7) is a vasodilator, that also inhibits proliferation and apoptosis . Beside the systemic effect on blood pressure regulation, ACE2 has local regulatory effects in the pathological changes of several organs, including the heart, kidney, and lungs . ACE2 is highly expressed in lung alveolar cells, providing the main entry site for the virus into human host . In addition to expression of ACE2 in lung alveolar cells, it is also expressed in various tissues, including: the vascular system (endothelial cells, migratory angiogenic cells and vascular smooth muscle cells), heart (cardiofibroblasts, cardiomyocytes, endothelial cells, pericytes, and epicardial adipose cells) and kidneys (glomerular endothelial cells, podocytes and proximal tubule epithelial cells), liver (cholangiocytes and hepatocytes), retina (pigmented epithelial cells, rod and cone photoreceptor cells, and Müller glial cells), enterocytes of the intestines, circumventricular organs of the central nervous system, and the upper airway (goblet and ciliated epithelial cells) .
There are two subunits of the SARS-CoV-2 S-protein: the S1 subunit has a receptor binding domain that engages with the host cell receptor ACE2, and the S2 subunit is involved in regulating fusion between the viral and the host membrane . It has been reported that SARS-CoV-2 has a ten times higher affinity to ACE2 compared to SARS-CoV, which is consistent with the higher efficiency of infection of SARS-CoV-2 . While no cure has currently been found, several clinical trials are being performed to determine what the most efficacious treatment regimen is for COVID-19, with an extensive list of potential therapies detailed in a review by Gosain et al. . Currently, patient management involves supportive treatment and measures to prevent further spread of the virus . Despite differences in patient population characteristics between Europe and China, two of the main determinants of patient mortality risk that were found in both groups are age and the presence of underlying comorbid conditions [14, 15]. One such underlying condition associated with an increase in COVID-19 patient mortality is the presence of cancer .