Lock, Stock and Barrel: Role of Renin-Angiotensin-Aldosterone System in Coronavirus Disease 2019

Christian Zanza,Fabrizio Racca,Mariele Montanari,Barbara Canonico,Veronica Ojetti,Chiara Robba,Fabio Piccolella,Loris Zamai,Angela Saviano,Michele Fidel Tassi,Tatsiana Romenskaya,Ludovico Abenavoli,Yaroslava Longhitano,Francesco Franceschi,Marco Artico,Andrea Piccioni

doi:10.3390/cells10071752

Abstract

Since the end of 2019, the medical-scientific community has been facing a terrible pandemic caused by a new airborne viral agent known as SARS-CoV2. Already in the early stages of the pandemic, following the discovery that the virus uses the ACE2 cell receptor as a molecular target to infect the cells of our body, it was hypothesized that the renin-angiotensin-aldosterone system was involved in the pathogenesis of the disease. Since then, numerous studies have been published on the subject, but the exact role of the renin-angiotensin-aldosterone system in the pathogenesis of COVID-19 is still a matter of debate. RAAS represents an important protagonist in the pathogenesis of COVID-19, providing the virus with the receptor of entry into host cells and determining its organotropism. Furthermore, following infection, the virus is able to cause an increase in plasma ACE2 activity, compromising the normal function of the RAAS. This dysfunction could contribute to the establishment of the thrombo-inflammatory state characteristic of severe forms of COVID-19. Drugs targeting RAAS represent promising therapeutic options for COVID-19 sufferers.

Highlights

Many research groups set themselves the goal of understanding whether and to what extent the renin-angiotensin-aldosterone system was involved in the pathogenesis of Coronavirus disease 2019 (COVID-19)
It is believed that these cells represent a fundamental actor in the pathogenesis of lung damage during COVID-19 [45,47,52,53,54]: the cytotoxic effects produced by the infection and replication of the virus in type II pneumocytes would determine their apoptosis, as well as the production of cytokines and chemokines with the recall of a massive cellular infiltrate of monocyte-macrophages and neutrophils and further release of cytotoxic and pro-inflammatory factors, in an actual cytokine storm
As it was discovered that angiotensin converting enzyme 2 (ACE2) is the receptor for SARS-CoV2 entry into the cells, many authors raised a concern for the potential negative interactions between RAAStargeting drugs (ACEI and ARBs) and SARS-Cov2: previous studies found that these medications may increase ACE2 levels, a fact that could potentially increase individual susceptibility to infection

Summary

Introduction

From the end of the year 2019, the world is struggling for a deadly pandemic used by a new emerging viral agent, known as SARS-Coronavirus 2 (SARS-CoV2), which have caused almost 2.5 million deaths so far [1]. It was soon evident that, likewise its predecessor SARS-CoV1, responsible for the 2002 outbreak, SARS-CoV2 is able to infect our cells thanks to the interaction with angiotensin converting enzyme II (ACE2) [2,3,4], a recently discovered transmembrane glycoprotein with enzymatic activity, belonging to the renin-angiotensin-aldosterone system (RAAS). Given these premises, many research groups set themselves the goal of understanding whether and to what extent the renin-angiotensin-aldosterone system was involved in the pathogenesis of Coronavirus disease 2019 (COVID-19). More than a year after the beginning of the pandemic, we review the current literature on the subject, trying to clarify what we think to know, what we are still trying to understand and where this can lead us

Renin-Angiotensin-Aldosterone System

RAAS Dysfunction in COVID-19 Pathogenesis

RAAS Targeting Drugs and COVID-19

Findings

Future Directions