SARS-CoV-2, ACE2 expression, and systemic organ invasion

Abstract

A novel coronavirus disease, COVID-19, has created a global pandemic in 2020, posing an enormous challenge to healthcare systems and affected communities. COVID-19 is caused by severe acute respiratory syndrome (SARS)-coronavirus-2 (CoV-2) that manifests as bronchitis, pneumonia, or a severe respiratory illness. SARS-CoV-2 infects human cells via binding a "spike" protein on its surface to angiotensin-converting enzyme 2 (ACE2) within the host. ACE2 is crucial for maintaining tissue homeostasis and negatively regulates the renin-angiotensin-aldosterone system (RAAS) in humans. The RAAS is paramount for normal function in multiple organ systems including the lungs, heart, kidney, and vasculature. Given that SARS-CoV-2 internalizes via ACE2, the resultant disruption in ACE2 expression can lead to altered tissue function and exacerbate chronic diseases. The widespread distribution and expression of ACE2 across multiple organs is critical to our understanding of the varied clinical outcomes of COVID-19. This perspective review based on the current literature was prompted to show how disruption of ACE2 by SARS-CoV-2 can affect different organ systems.

Keywords: ACE2; COVID-19; RAAS; SARS-CoV-2; complex disease.

Figure 1.

Novel therapies involving ACE2 in the treatment of COVID-19. Novel therapeutics have been proposed that target/utilize ACE2’s role as the entry receptor for SARS-CoV-2. Prophylactic treatments involve the use of fusion inhibitors that disrupt the viral membrane union and coronavirus-neutralizing antibodies that target spike proteins to prevent ACE2 attachment and interaction with the host cell. For therapeutic treatments, recombinant ACE2 has proven beneficial in attenuating lung injury, which may reduce severe symptoms exhibited in many patients with COVID-19. ACE2, angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2.

Figure 2.

An organ review of normal ACE2 function versus potential pathophysiological consequences of ACE2 disruption caused by SARS-CoV-2 infection. ACE2 is present in various tissues, and its expression is vital to normal physiological functions. ACE2 disruption initiated through the binding of SARS-CoV-2 may have short- and long-term pathophysiological consequences to numerous organ systems that utilize ACE2 for proper function. ACE2, angiotensin-converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome-coronavirus-2.