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Renin-Angiotensin-Aldosterone Inhibitors and Susceptibility to and Severity of COVID-19

Educational Objective
To understand renin-angiotensin-aldosterone inhibitors and susceptibility to and severity of COVID-19

The biological mechanisms by which severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus that causes coronavirus disease 2019 (COVID-19), enters human cells have been identified in detail.1 The key viral protein involved in cell entry is the spike (S) protein located on the surface of the virus particle. Two host-cell proteins, angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine S2 (TMPRSS2), are also critical for cell entry. The viral S protein binds to ACE2, which serves as the cell membrane receptor for SARS-CoV-2, but only after the S protein has been “primed” by the action of the serine protease TMPRSS2. Thus, the host enzymes, ACE2 and TMPRSS2, act in concert to facilitate viral entry, setting the stage for the development of COVID-19.

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Article Information

Published Online: June 19, 2020. doi:10.1001/jama.2020.11401

Corresponding Author: Gregory Curfman, MD, JAMA, 330 N Wabash, Chicago, IL 60611 (gregory.curfman@jamanetwork.org).

Conflict of Interest Disclosures: None reported.

References
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Hoffmann  M , Kleine-Weber  H , Schroeder  S ,  et al.  SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor.   Cell. 2020;181(2):271-280.e8. doi:10.1016/j.cell.2020.02.052PubMedGoogle ScholarCrossref
2.
Sukumaran  V , Tsuchimochi  H , Tatsumi  E , Shirai  M , Pearson  JT .  Azilsartan ameliorates diabetic cardiomyopathy in young db/db mice through the modulation of ACE-2/ANG 1-7/Mas receptor cascade.   Biochem Pharmacol. 2017;144:90-99. doi:10.1016/j.bcp.2017.07.022PubMedGoogle ScholarCrossref
3.
Fosbøl  EL , Butt  JH , Østergaard  L ,  et al.  Association of angiotensin-converting enzyme inhibitor or angiotensin receptor blocker use with COVID-19 diagnosis and mortality.   JAMA. Published online June 19, 2020. doi:10.1001/jama.2020.11301Google Scholar
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Mehta  N , Kalra  A , Nowacki  AS ,  et al.  Association of use of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers with testing positive for coronavirus disease 2019 (COVID-19).   JAMA Cardiol. Published online May 5, 2020. doi:10.1001/jamacardio.2020.1855PubMedGoogle Scholar
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Patel  AB , Verma  A .  COVID-19 and angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what is the evidence?   JAMA. 2020;323(18):1769-1770. doi:10.1001/jama.2020.4812PubMedGoogle Scholar
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Mancia  G , Rea  F , Ludergnani  M , Apolone  G , Corrao  G .  Renin—angiotensin—aldosterone blockers and the risk of COVID-19.   N Engl J Med. Published online May 1, 2020. doi:10.1056/NEJMoa2006923PubMedGoogle Scholar
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Reynolds  HR , Adhikari  S , Pulgarin  C ,  et al.  Renin—angiotensin—aldosterone inhibitors and risk of COVID-19.   N Engl J Med. Published online May 1, 2020. doi:10.1056/NEJMoa2008975PubMedGoogle Scholar
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Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

  • 1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
  • 1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
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  • 1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
  • 1.00 credit toward the CME [and Self-Assessment requirements] of the American Board of Surgery’s Continuous Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.

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