Fig. 2.

Altered balance between the classical and regulatory parts of the renin-angiotensin system (RAS) in COVID-19. a Ang-II is formed by the ACE-1-mediated cleavage of Ang-I. The binding of Ang-II to AT1R within the vasculature not only induces vasoconstriction but also affects vascular permeability and neurovascular coupling and promotes neuroinflammation and oxidative stress within the CNS. Under normal circumstances, these actions are counteracted by ACE-2 activity, which leads to the production of Ang-1-9 and Ang-(1-7) and the activation of MasR. b Internalisation or cleavage of membrane-bound ACE-2 following the binding and cell entry of SARS-CoV-2 virus leads to downregulation of the regulatory RAS and overaction of the classical RAS, driving vascular dysfunction, inflammation, oxidative stress and CNS injury in COVID-19