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Review
. 2020 Jun 12;134(11):1259-1264.
doi: 10.1042/CS20200492.

Covid-19: the renin-angiotensin system imbalance hypothesis

Katharina Lanza  1 , Lucas G Perez  1 , Larissa B Costa  1 , Thiago M Cordeiro  1 , Vitria A Palmeira  1 , Victor T Ribeiro  1 , Ana Cristina Simões E Silva  1
Affiliations
Review

Covid-19: the renin-angiotensin system imbalance hypothesis

Katharina Lanza et al. Clin Sci (Lond). .

Abstract

The emergency of SARS-CoV-2 in China started a novel challenge to the scientific community. As the virus turns pandemic, scientists try to map the cellular mechanisms and pathways of SARS-CoV-2 related to the pathogenesis of Coronavirus Disease 2019 (Covid-19). After transmembrane angiotensin-converting enzyme 2 (ACE2) has been found to be SARS-CoV-2 receptor, we hypothesized an immune-hematological mechanism for Covid-19 based on renin-angiotensin system (RAS) imbalance to explain clinical, laboratory and imaging findings on disease course. We believe that exaggerated activation of ACE/Angiotensin II (Ang II)/Angiotensin Type 1 (AT1) receptor RAS axis in line with reduction of ACE2/Angiotensin-(1-7)/Mas receptor may exert a pivotal role in the pathogenesis of Covid-19. In this perspective, we discuss potential mechanisms and evidence on this hypothesis.

Keywords: Angiotensin-Converting Enzyme 2; Covid-19; Renin-Angiotensin System; SARS-CoV-2.

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Conflict of interest statement

The authors declare that there are no competing interests associated with the manuscript.

Figures

Figure 1
Figure 1. Pathophysiological role of ACE2 in COVID-19
Schematic representation of pathophysiological mechanisms related to COVID-19 and the overlapping pathways with renin–angiotensin system, particularly with the modulation of ACE2. [O2] = Oxygen concentration; HS = Hemophagocytic-like Syndrome; ACE2 = Angiotensin-Converting Enzyme 2; ANG(1-7) = Angiotensin (1-7); ANGII = Angiotensin II; HPSC = Hematopoietic stem/progenitor cell.
Figure 2
Figure 2. ACE2 basis for age specific differences in COVID-19 outcome
Schematic representation of the differences detected in ACE2 expression according to age. The figure highlights the hypothetical mechanisms related to COVID-19 outcome based on the protective effects of free ACE2 for buffering the viral infection as well as reducing inflammation. ACE2, angiotensin-converting enzyme 2; ANG(1-7), angiotensin (1-7); ANGII, Angiotensin II.
See this image and copyright information in PMC

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