Pathophysiology of COVID-19: Everywhere You Look You Will See ACE2!

Abstract

Angiotensin converting enzyme 2 (ACE₂) seems to be a central actor in the pathophysiology of SARS-Cov-2 infection. First, it acts as the receptor for the virus and permits its attachment to cells expressing ACE₂. Second, the relative deficiency of ACE₂ during infection could be linked to several clinical features encountered during the disease, like ARDS and coagulation abnormalities. This study explores the strong link between ACE₂ and the majority of risk factors for the severe evolution of COVID-19. It seems that all these risks factors are linked to an increased level of ACE₂ and/or imbalance in ACE/ACE₂.

Keywords: COVID-19 pandemic; SARS – CoV – 2; angiotensin-converting enzyme; bradykinin - analogs and derivatives; lung injury; pathophysiology.

Figure 1

ACE/ACE2 imbalance and effect in case of SARS-CoV-2 infection. SARS-CoV-2 spike protein ligates angiotensin conversion enzyme 2 (ACE₂) and leads to a relative deficiency in ACE₂. Such deficiency leads to both an imbalance in the ACE/ACE₂ system and an over activation of the ACE pathway with over production of angiotensin 2 (Ang II) ligating the receptor AT1R. The present fact leads to a global pro-inflammatory, pro-fibrotic, and pro-oxidative state (in red). ACE₂, through degradation of Ang II to angiotensin 1–7, leads to both a decrease in Ang II levels and stimulation of anti-inflammatory and anti-fibrotic pathways via AT2R and MasR (in green). Moreover, ACE₂ inactivate des-Arg-Bradykinin (DABK), which in the case of ligation to receptor Bradykinine-B1-receptor (BkB1R) leads to inflammation and vascular permeability (red arrow). In this regard, the final result of ACE₂ deficiency is both the promotion of lung inflammation and a decrease in lung anti-inflammatory effects, inducing SARS-CoV-2 acute respiratory syndrome.