Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the pathogen of coronavirus disease 2019 (COVID‐19), caused the outbreak escalated to pandemic. Reports suggested that near 1–3% of COVID‐19 cases have a fatal outcome. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are widely used in hypertension, heart failure and chronic kidney disease. These drugs have been reported to upregulate angiotensin converting enzyme 2 (ACE2) which produces Ang (1–7), the main counter-regulatory mediator of angiotensin II. This enzyme is also known as the receptor of SARS‐CoV‐2 promoting the cellular uptake of the virus in the airways, however, ACE2 itself proved to be protective in several experimental models of lung injury. The present study aimed to systematically review the relationship between ACEI/ARB administration and ACE2 expression in experimental models. After a comprehensive search and selection, 27 animal studies investigating ACE2 expression in the context of ACEI and ARB were identified. The majority of these papers reported increased ACE2 levels in response to ACEI/ARB treatment. This result should be interpreted in the light of the dual role of ACE2 being a promoter of viral entry to cells and a protective factor against oxidative damage in the lungs.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), was first reported to cause human infection in Wuhan, China, in December 2019 (Tan et al, 2020)
Since angiotensinconverting enzyme 2 (ACE2) was identified as the receptor of SARS-CoV-2 (Hoffmann et al, 2020; Zhou et al, 2020), ACE2 upregulation with facilitated viral uptake might aggravate lung injury and fatal outcome in the case of COVID-19
Recent clinical reports (Diaz, 2020) and reviews (Fang et al, 2020) on the COVID-19 pandemic raised such concerns without systematic analysis of results from animal and human studies leading to premature conclusions and even panic among physicians and patients taking angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs)
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the pathogen of coronavirus disease 2019 (COVID-19), was first reported to cause human infection in Wuhan, China, in December 2019 (Tan et al, 2020). Reports suggested that 1–3% of COVID-19 cases have a fatal outcome which prompted physicians and healthcare professionals to seek prognostic factors. Advanced age and cardiovascular comorbidities were confirmed to be associated with a severe form of the disease (Zhang et al, 2020) and angiotensin-converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs) widely used in the treatment of cardiovascular diseases were implicated as well (Diaz, 2020). The reason for the latter is that the angiotensinconverting enzyme 2 (ACE2), known to be the receptor of both SARS-CoV-1 and SARS-CoV-2 (Li et al, 2003; Hoffmann et al, 2020; Zhou et al, 2020), might be overexpressed in patients taking ACEIs or ARBs potentially promoting the cellular uptake of the coronavirus in the airways
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