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Review
. 2020 Sep;57(5):339-350.
doi: 10.1177/0004563220928361. Epub 2020 Jun 2.

Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

Annalise E Zemlin  1 , Owen J Wiese  1
Affiliations
Review

Coronavirus disease 2019 (COVID-19) and the renin-angiotensin system: A closer look at angiotensin-converting enzyme 2 (ACE2)

Annalise E Zemlin et al. Ann Clin Biochem. 2020 Sep.

Abstract

Since the first cases of atypical pneumonia linked to the Huanan Seafood Wholesale Market in Wuhan, China, were described in late December 2019, the global landscape has changed radically. In March 2020, the World Health Organization declared COVID-19 a global pandemic, and at the time of writing this review, just over three million individuals have been infected with more than 200,000 deaths globally. Numerous countries are in 'lockdown', social distancing is the new norm, even the most advanced healthcare systems are under pressure, and a global economic recession seems inevitable. A novel coronavirus (SARS-CoV-2) was identified as the aetiological agent. From experience with previous coronavirus epidemics, namely the severe acute respiratory syndrome (SARS) and Middle East Respiratory Syndrome (MERS) in 2004 and 2012 respectively, it was postulated that the angiotensin-converting enzyme-2 (ACE2) receptor is a possible port of cell entry. ACE2 is part of the renin-angiotensin system and is also associated with lung and cardiovascular disorders and inflammation. Recent studies have confirmed that ACE2 is the port of entry for SARS-CoV-2. Male sex, advanced age and a number of associated comorbidities have been identified as risk factors for infection with COVID-19. Many high-risk COVID-19 patients with comorbidities are on ACE inhibitors and angiotensin receptor blockers, and this has sparked debate about whether to continue these treatment regimes. Attention has also shifted to ACE2 being a target for future therapies or vaccines against COVID-19. In this review, we discuss COVID-19 and its complex relationship with ACE2.

Keywords: COVID-19; SARS-CoV-2; angiotensin-converting enzyme 2; renin-angiotensin system.

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Figures

Figure 1.
Figure 1.
A timeline illustrating the most notable events of the COVID-19 outbreak.Source: World Health Organization (WHO).
Figure 2.
Figure 2.
RAS pathway showing various receptors and their effects. Also shown are mechanisms of action for ACE inhibitors and ARB.27,29RAS: Renin Angiotensin System; ACEi: Angiotensin Converting Enzyme inhibitor; ARB: Angiotensin Receptor Blocker; AT1: Angiotensin 1; AT2: Angiotensin 2.
Figure 3.
Figure 3.
Entry of SARS-CoV-2 into host cells using ACE2 Receptor and TMPRSS2 to gain entry.51SARS-Co-V-2: Severe Acute Respiratory Syndrome-Coronavirus-2; ACE2: Angiotensin Converting Enzyme 2; TMPRSS2: transmembrane protease, serine 2.
See this image and copyright information in PMC

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