COVID-19 and relative angiotensin-converting enzyme 2 deficiency: role in disease severity and therapeutic response

• Published in: Open heart 2020-06, Vol.7 (1), p.e001302
• Main Authors: Ryan, Paul MacDaragh, Caplice, Noel
• Format: Article
• Language: English
• Subjects: Cardiovascular disease; Coronaviruses; COVID-19; Viewpoint; Viral infections
• ISSN: 2053-3624; 2398-595X; 2053-3624
• DOI: 10.1136/openhrt-2020-001302

In this viewpoint, we underscored specific alterations in renin angiotensin system-ACE 2 (RAS-ACE2) homeostasis that may contribute to more adverse COVID-19 outcomes in patients with pre-existing cardiovascular disease. [...]we proposed and developed a rationale for specific therapeutic interventions that might mitigate some of the more deleterious cellular pathology and cardiovascular effects of this syndrome. The primary role of ACE2 in health is maturation of angiotensin, a peptide implicated in vascular homeostasis, vasomotor tone and blood pressure regulation.7 Importantly ACE2 is expressed on diverse human cells including epithelial cells in the lung and small and large intestines, tubular cells of the kidney, vascular endothelial and smooth muscle cells and cardiomyocytes (figure 2)9 and reduction in ACE2 is well known to be associated with hypertension, diabetes, coronary artery disease, myocardial infarct repair and heart failure.10 Figure 2. Interestingly, comparative analysis of two successive SARS epidemics in early 2000s showed that increased affinity of the SARS virus for human ACE2 receptor strongly predicted severity of clinical disease suggesting that spike protein conformation is potentially a key determinant of virulence.14 Moreover, the spike protein present on SARS-CoV and SARS-CoV-2 facilitates host cell-to-cell fusion to form syncytia that may have potential pathological consequences for tissues such as the heart.15 Interestingly, in several Wuhan cohorts cardiac injury and arrythmia were prominent in high-risk COVID-19 subjects.1 3 4 Previous SARS-CoV studies also indicated that clinical and pathological impacts of viral infection in various tissues and organs are determined not solely by viral load or tropism with respect to cell surface receptors but also by the counter-regulatory pathways within the host.16 These host mechanisms include inter alia complex elements of homeostatic and inflammatory pathways, anti-apoptotic responses and the compensatory repair power or functional reserve of tissues and organs within the infected subject. [...]ACE2 represents an endogenous counter-regulatory pathway with RAS and acts in opposition to the ACE axis (figure 3).