Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19

Abstract

An outbreak of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that started in Wuhan, China, at the end of 2019 has become a global pandemic. Both SARS-CoV-2 and SARS-CoV enter host cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which is expressed in various human organs. We have reviewed previously published studies on SARS and recent studies on SARS-CoV-2 infection, named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), confirming that many other organs besides the lungs are vulnerable to the virus. ACE2 catalyzes angiotensin II conversion to angiotensin-(1–7), and the ACE2/angiotensin-(1–7)/MAS axis counteracts the negative effects of the renin-angiotensin system (RAS), which plays important roles in maintaining the physiological and pathophysiological balance of the body. In addition to the direct viral effects and inflammatory and immune factors associated with COVID-19 pathogenesis, ACE2 downregulation and the imbalance between the RAS and ACE2/angiotensin-(1–7)/MAS after infection may also contribute to multiple organ injury in COVID-19. The SARS-CoV-2 spike glycoprotein, which binds to ACE2, is a potential target for developing specific drugs, antibodies, and vaccines. Restoring the balance between the RAS and ACE2/angiotensin-(1–7)/MAS may help attenuate organ injuries. Graphical abstract SARS-CoV-2 enters lung cells via the ACE2 receptor. The cell-free and macrophage-phagocytosed virus can spread to other organs and infect ACE2-expressing cells at local sites, causing multi-organ injury.

The Fundamental Role of Prophylactic Anticoagulation Therapy and the Complications of Hypercoagulability in Patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)

“…Also, venous thromboembolism has been demonstrated on both microvascular and macrovascular scales in published post-partum studies in COVID-19 patients [7]. The pathophysiology of this is still very much under investigation but various hypotheses have touched upon the possibility of the immuno-thrombotic phenomeno [1]. McGonagle et al suggests that the binding of SARS-CoV-2 to the angiotensin-converting enzyme 2 (ACE2) ultimately leads to a generalized pulmonary hypercoagulable state due to activation of type II pneumocytes propagating an in ammatory cascade [8,9].…”

“…Coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease that result in acute respiratory distress, multiorgan failure, in part due to the complex role of SARS-CoV-2 and its angiotensin-converting enzyme 2 (ACE2) receptor binding capacity [1]. This marked a nity of the virus has been associated with the downregulation of ACE2 enzyme and the disruption of physiological and pathophysiological homeostasis.…”

Angiotensin Converting Enzyme 2 in COVID-19 infections and the implications of COVID-19 on major body systems

“…This spike glycogen structure contains a receptor binding domain which interacts with subdomain I of ACE-2. Cell entry of the virus is then facilitated by priming of the serine protease TMPRSS2 16,17 . ACE-2 can be identified in different organs of the body.…”

“…It is established that in the lungs, ACE-2 is mainly found on type II alveolar epithelial cells and even though it is also found in the mucosal layer of the oral cavity, nasal cavity and nasopharynx, it is only weakly expressed in these areas of the body 12,18 . Although evidence suggests that the lung is the main target site for SARS-CoV-2 infections, it is also possible for other organs of the body, such as the heart, kidneys and gastrointestinal (GI) tract, to be affected by this virus as they also express ACE-2 in varying degrees 17 .…”

“…In COVID-19, the increased levels of Ang II following a downregulation of ACE-2 expression, causes an over stimulation of the RAS. The protective effects of the ACE-2/ Ang-(1-7)/Mas pathway is reduced and cardiac injury may therefore be promoted 17 .…”