RAS Inhibitors Might Be a Good Choice for the Therapy of COVID-19 Pneumonia

Original Article: Meili Sun, Jianmin Yang, Yuping Sun, Guohai Su. ; Inhibitors of RAS Might Be a Good Choice for the Therapy of COVID-19 Pneumonia

Article Translation: Zhi Liu; Revision: Qiaoshi Lian; Edits: Federica La Russa; Summary: Qiaoshi Lian; Revision and Italian Translation: Federica La Russa

Original Article Published on February 16th, 2020

In this predictive paper, the authors provide a framework around the modulation of the Renin-Angiotensin-System (RAS) as potential strategy to manage pneumonia in COVID-19 patients.

  • The Angiotensin-Converting Enzyme 2 (ACE2) has been identified as the binding receptor of SARS-CoV-2.
  • ACE2 is considered an important antagonist of ACE/Ang-II/AT1R axis, which could induce proinflammatory, pro-proliferative, pro-fibrotic effects linked to lung inflammation.
  • At steady state, ACE2 is essential to balance ACE/Ang-II/AT1R via two major processes: 1. ACE2 cleaves Ang-II to Ang-(1-7); 2. Ang-(1-7) couples with Mas receptors to trigger anti-inflammatory effects.
  • During acute lung injury, ACE activity and Ang-II expression are enhanced, while ACE2 activity and Ang-(1-7) levels are reduced, thus resulting in overactivation of the ACE/Ang-II/AT1R axis, which in turn leads to severe inflammation in lung pneumonia in animal models.
  • Clinical studies have shown that serum levels of Ang-II are significantly elevated in patients with acute lung injury, especially in pneumonia caused by H5N1 virus infection, and high serum levels of Ang-II are associated with the severity and lethality of the infection.
  • In the light of this, both activation of ACE2/Ang-(1-7)/Mas signaling pathway and inhibition of ACE/Ang-II/AT1R pathway might represent good options for COVID-19 treatment to limit lung inflammation, and in turn, patient mortality. Candidate strategies include: increasing exogenous Ang-(1-7); activating Mas receptors; inhibitors of ACE/Ang-II/AT1R pathway with either ACE inhibitors (e.g. Captopril, Enalapril) o AT1R inhibitors (e.g. Losartan, Valsartan).
  • Notably, due to the role of RAS in the maintaining cardiovascular homeostasis, such treatments should be considered under close monitoring of blood pressure.

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