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SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy.
EBioMedicine. 2020 Aug; 58:102907.E

Abstract

BACKGROUND

SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful.

METHODS

Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed.

FINDINGS AND INTERPRETATION

SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets.

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Authors+Show Affiliations

Chung MK
Heart, Vascular and Thoracic Institute, United States; Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States. Electronic address: chungm@ccf.org.
Karnik S
Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Saef J
Heart, Vascular and Thoracic Institute, United States.
Bergmann C
Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Barnard J
Lerner Research Institute, Cleveland Clinic, United States.
Lederman MM
Case Western Reserve University, United States; University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
Tilton J
Case Western Reserve University, United States.
Cheng F
Lerner Research Institute, Cleveland Clinic, United States.
Harding CV
Case Western Reserve University, United States; University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
Young JB
Heart, Vascular and Thoracic Institute, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Mehta N
Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Cameron SJ
Heart, Vascular and Thoracic Institute, United States; Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States.
McCrae KR
Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States.
Schmaier AH
Case Western Reserve University, United States; University Hospitals Cleveland Medical Center, Cleveland, OH, United States.
Smith JD
Lerner Research Institute, Cleveland Clinic, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Kalra A
Heart, Vascular and Thoracic Institute, United States.
Gebreselassie SK
Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Thomas G
Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Hawkins ES
Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.
Svensson LG
Heart, Vascular and Thoracic Institute, United States; Cleveland Clinic Lerner College of Medicine, United States; Case Western Reserve University, United States.

MeSH

Angiotensin Receptor AntagonistsAngiotensin-Converting Enzyme 2Angiotensin-Converting Enzyme InhibitorsAnimalsBetacoronavirusCOVID-19Coronavirus InfectionsHumansKallikrein-Kinin SystemPandemicsPeptidyl-Dipeptidase APneumonia, ViralRenin-Angiotensin SystemSARS-CoV-2

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32771682

Citation

Chung, Mina K., et al. "SARS-CoV-2 and ACE2: the Biology and Clinical Data Settling the ARB and ACEI Controversy." EBioMedicine, vol. 58, 2020, p. 102907.
Chung MK, Karnik S, Saef J, et al. SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine. 2020;58:102907.
Chung, M. K., Karnik, S., Saef, J., Bergmann, C., Barnard, J., Lederman, M. M., Tilton, J., Cheng, F., Harding, C. V., Young, J. B., Mehta, N., Cameron, S. J., McCrae, K. R., Schmaier, A. H., Smith, J. D., Kalra, A., Gebreselassie, S. K., Thomas, G., Hawkins, E. S., & Svensson, L. G. (2020). SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. EBioMedicine, 58, 102907. https://doi.org/10.1016/j.ebiom.2020.102907
Chung MK, et al. SARS-CoV-2 and ACE2: the Biology and Clinical Data Settling the ARB and ACEI Controversy. EBioMedicine. 2020;58:102907. PubMed PMID: 32771682.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - SARS-CoV-2 and ACE2: The biology and clinical data settling the ARB and ACEI controversy. AU - Chung,Mina K, AU - Karnik,Sadashiva, AU - Saef,Joshua, AU - Bergmann,Cornelia, AU - Barnard,John, AU - Lederman,Michael M, AU - Tilton,John, AU - Cheng,Feixiong, AU - Harding,Clifford V, AU - Young,James B, AU - Mehta,Neil, AU - Cameron,Scott J, AU - McCrae,Keith R, AU - Schmaier,Alvin H, AU - Smith,Jonathan D, AU - Kalra,Ankur, AU - Gebreselassie,Surafel K, AU - Thomas,George, AU - Hawkins,Edward S, AU - Svensson,Lars G, Y1 - 2020/08/06/ PY - 2020/5/15/received PY - 2020/6/20/revised PY - 2020/7/7/accepted PY - 2020/8/11/pubmed PY - 2020/9/4/medline PY - 2020/8/11/entrez KW - ACE inhibitors KW - ACE2 KW - ARBs KW - COVID-19 KW - Kallikrein-kinin system KW - Renin-angiotensin system KW - SARS-CoV-2 SP - 102907 EP - 102907 JF - EBioMedicine JO - EBioMedicine VL - 58 N2 - BACKGROUND: SARS-CoV-2 enters cells by binding of its spike protein to angiotensin-converting enzyme 2 (ACE2). Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) have been reported to increase ACE2 expression in animal models, and worse outcomes are reported in patients with co-morbidities commonly treated with these agents, leading to controversy during the COVID-19 pandemic over whether these drugs might be helpful or harmful. METHODS: Animal, in vitro and clinical data relevant to the biology of the renin-angiotensin system (RAS), its interaction with the kallikrein-kinin system (KKS) and SARS-CoV-2, and clinical studies were reviewed. FINDINGS AND INTERPRETATION: SARS-CoV-2 hijacks ACE2to invade and damage cells, downregulating ACE2, reducing its protective effects and exacerbating injurious Ang II effects. However, retrospective observational studies do not show higher risk of infection with ACEI or ARB use. Nevertheless, study of the RAS and KKS in the setting of coronaviral infection may yield therapeutic targets. SN - 2352-3964 UR - https://www.unboundmedicine.com/medline/citation/32771682/SARS_CoV_2_and_ACE2:_The_biology_and_clinical_data_settling_the_ARB_and_ACEI_controversy_ DB - PRIME DP - Unbound Medicine ER -