# The Counter-Regulatory Renin-Angiotensin System: A Surprising Ally in the Field of COVID-19

## TL;DR

This review explores how components of the renin-angiotensin system, like ACE2 and Ang peptides, may protect against severe COVID-19 effects and suggest new therapeutic approaches.

## Contribution

The paper highlights the novel therapeutic potential of balancing Ang-(1-7) and Ang-(1-9) to counteract SARS-CoV-2-induced complications.

## Key findings

- Ang-(1-7) and Ang-(1-9) may protect against heart damage by counteracting angiotensin II's harmful effects.
- ACE2 plays a dual role in both viral entry and protection, influencing disease severity and treatment outcomes.
- More clinical trials are needed to confirm the protective effects of Ang peptides in COVID-19 patients.

## Abstract

Over the past four years, SARS-CoV-2 and COVID-19 have become global health crises, spurring extensive research on virus behavior, complications, and treatments. The virus interacts with a component of the renin-angiotensin system (RAS), altering inflammatory, hypertrophic, and hemodynamic responses via binding to ACE2 found in organs like the heart, lungs, and kidneys.

This review explores the RAS-COVID-19 interplay, focusing on key molecules like ACE2, Ang-(1-7), and Ang-(1-9), influencing susceptibility, severity, and treatments. It seeks to clarify ACE2's dual role in viral entry and protection and assess the therapeutic potential of balancing Ang-(1-7) and Ang-(1-9) to prevent disease progression and related complications.

Studies were chosen through a systematic search in databases, such as PubMed, Scopus, and Web of Science. The inclusion criteria were centered on peer-reviewed research that explored the relationship between SARS-CoV-2 and important RAS molecules, including ACE2, Ang-(1–7), and Ang-(1-9), seeking information on therapies, severity, and susceptibility. Non-peer-reviewed articles and those lacking focus on RAS-COVID-19 interplay were excluded. Titles and abstracts were screened, followed by full-text assessment and data extraction for analysis.

Some studies indicate that the peptides Ang-(1-7) and Ang-(1-9) could provide protective effects against heart-related complications by counteracting the harmful impacts of the angiotensin II pathway, which is often exacerbated by SARS-CoV-2. Ang-(1-7) and Ang-(1-9) are recognized for promoting vasodilation, reducing inflammation, and preventing fibrosis, which can mitigate the heart damage typically associated with COVID-19.

ACE2, a component of the non-canonical RAS, is closely linked to SARS-CoV-2 and plays a pivotal role in the pathophysiology of COVID-19. Ang-(1-9) and Ang-(1-7) are produced by ACE2 and have demonstrated positive cardiovascular effects. In the context of COVID-19, Ang-(1-7) has shown protective effects in preclinical studies and clinical trials; however, more evidence is needed to support this effect.

Further research, including clinical trials, is vital to understand and develop precise therapies for COVID-19 and similar infectious diseases.