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Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19).
J Pathol. 2020 07; 251(3):228-248.JP

Abstract

Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

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Authors+Show Affiliations

Bourgonje AR
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Abdulle AE
Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Timens W
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Hillebrands JL
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Navis GJ
Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Gordijn SJ
Department of Obstetrics and Gynecology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Bolling MC
Department of Dermatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Dijkstra G
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Voors AA
Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Osterhaus AD
Research Center for Emerging Infections and Zoonoses, University of Veterinary Medicine, Hannover, Germany.
van der Voort PH
Department of Critical Care Medicine, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Mulder DJ
Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
van Goor H
Department of Pathology and Medical Biology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.

MeSH

Age FactorsAngiotensin-Converting Enzyme 2Antiviral AgentsBetacoronavirusCOVID-19Cardiovascular DiseasesCoronavirus InfectionsDisease ProgressionHumansMetabolic SyndromeMorbidityPandemicsPeptidyl-Dipeptidase APneumonia, ViralRenin-Angiotensin SystemRisk FactorsSARS-CoV-2Sex Factors

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

32418199

Citation

Bourgonje, Arno R., et al. "Angiotensin-converting Enzyme 2 (ACE2), SARS-CoV-2 and the Pathophysiology of Coronavirus Disease 2019 (COVID-19)." The Journal of Pathology, vol. 251, no. 3, 2020, pp. 228-248.
Bourgonje AR, Abdulle AE, Timens W, et al. Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). J Pathol. 2020;251(3):228-248.
Bourgonje, A. R., Abdulle, A. E., Timens, W., Hillebrands, J. L., Navis, G. J., Gordijn, S. J., Bolling, M. C., Dijkstra, G., Voors, A. A., Osterhaus, A. D., van der Voort, P. H., Mulder, D. J., & van Goor, H. (2020). Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). The Journal of Pathology, 251(3), 228-248. https://doi.org/10.1002/path.5471
Bourgonje AR, et al. Angiotensin-converting Enzyme 2 (ACE2), SARS-CoV-2 and the Pathophysiology of Coronavirus Disease 2019 (COVID-19). J Pathol. 2020;251(3):228-248. PubMed PMID: 32418199.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19). AU - Bourgonje,Arno R, AU - Abdulle,Amaal E, AU - Timens,Wim, AU - Hillebrands,Jan-Luuk, AU - Navis,Gerjan J, AU - Gordijn,Sanne J, AU - Bolling,Marieke C, AU - Dijkstra,Gerard, AU - Voors,Adriaan A, AU - Osterhaus,Albert Dme, AU - van der Voort,Peter Hj, AU - Mulder,Douwe J, AU - van Goor,Harry, Y1 - 2020/06/10/ PY - 2020/04/26/received PY - 2020/05/12/revised PY - 2020/05/14/accepted PY - 2020/5/18/pubmed PY - 2020/9/8/medline PY - 2020/5/18/entrez KW - angiotensin-converting enzyme 2 (ACE2) KW - coronavirus disease 2019 (COVID-19) KW - organ involvement KW - pathology KW - pathophysiology KW - renin-angiotensin-aldosterone system (RAAS) KW - risk factors KW - severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) KW - treatment SP - 228 EP - 248 JF - The Journal of pathology JO - J Pathol VL - 251 IS - 3 N2 - Angiotensin-converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID-19). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter-regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin-angiotensin-aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID-19 severity and progression, including age, sex, ethnicity, medication, and several co-morbidities, such as cardiovascular disease and metabolic syndrome. Although ACE2 is widely distributed in various human tissues and many of its determinants have been well recognised, ACE2-expressing organs do not equally participate in COVID-19 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID-19 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS-CoV-2 infection is crucially important as it has major implications for understanding COVID-19 pathophysiology and the development of evidence-based treatment strategies. Currently, many interventional strategies are being explored in ongoing clinical trials, encompassing many drug classes and strategies, including antiviral drugs, biological response modifiers, and RAAS inhibitors. Ultimately, prevention is key to combat COVID-19 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID-19 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID-19 severity. In addition, we discuss the relevant pathological changes resulting from SARS-CoV-2 infection. Finally, we highlight a selection of potential treatment modalities for COVID-19. © 2020 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. SN - 1096-9896 UR - https://www.unboundmedicine.com/medline/citation/32418199/Angiotensin_converting_enzyme_2__ACE2__SARS_CoV_2_and_the_pathophysiology_of_coronavirus_disease_2019__COVID_19__ DB - PRIME DP - Unbound Medicine ER -