{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T23:47:31Z","timestamp":1792799251701,"version":"4.5.0"},"reference-count":227,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2020,6,10]],"date-time":"2020-06-10T00:00:00Z","timestamp":1591747200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["pathsocjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Pathology"],"published-print":{"date-parts":[[2020,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Angiotensin\u2010converting enzyme 2 (ACE2) has been established as the functional host receptor for severe acute respiratory syndrome coronavirus 2 (SARS\u2010CoV\u20102), the virus responsible for the current devastating worldwide pandemic of coronavirus disease 2019 (COVID\u201019). ACE2 is abundantly expressed in a variety of cells residing in many different human organs. In human physiology, ACE2 is a pivotal counter\u2010regulatory enzyme to ACE by the breakdown of angiotensin II, the central player in the renin\u2013angiotensin\u2013aldosterone system (RAAS) and the main substrate of ACE2. Many factors have been associated with both altered ACE2 expression and COVID\u201019 severity and progression, including age, sex, ethnicity, medication, and several co\u2010morbidities, 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\u2010expressing organs do not equally participate in COVID\u201019 pathophysiology, implying that other mechanisms are involved in orchestrating cellular infection resulting in tissue damage. Reports of pathologic findings in tissue specimens of COVID\u201019 patients are rapidly emerging and confirm the established role of ACE2 expression and activity in disease pathogenesis. Identifying pathologic changes caused by SARS\u2010CoV\u20102 infection is crucially important as it has major implications for understanding COVID\u201019 pathophysiology and the development of evidence\u2010based 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\u201019 and appropriate measures are being taken accordingly, including development of effective vaccines. In this review, we describe the role of ACE2 in COVID\u201019 pathophysiology, including factors influencing ACE2 expression and activity in relation to COVID\u201019 severity. In addition, we discuss the relevant pathological changes resulting from SARS\u2010CoV\u20102 infection. Finally, we highlight a selection of potential treatment modalities for COVID\u201019. \u00a9 2020 The Authors.\n                    <jats:italic>The Journal of Pathology<\/jats:italic>\n                    published by John Wiley &amp; Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.\n                  <\/jats:p>","DOI":"10.1002\/path.5471","type":"journal-article","created":{"date-parts":[[2020,5,17]],"date-time":"2020-05-17T12:14:54Z","timestamp":1589717694000},"page":"228-248","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":966,"title":["Angiotensin\u2010converting enzyme 2 (\n                    <scp>ACE2<\/scp>\n                    ),\n                    <scp>SARS\u2010CoV<\/scp>\n                    \u20102 and the pathophysiology of coronavirus disease 2019 (\n                    <scp>COVID<\/scp>\n                    \u201019)"],"prefix":"10.1002","volume":"251","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5754-3821","authenticated-orcid":false,"given":"Arno R","family":"Bourgonje","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amaal E","family":"Abdulle","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Vascular Medicine, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4146-6363","authenticated-orcid":false,"given":"Wim","family":"Timens","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan\u2010Luuk","family":"Hillebrands","sequence":"additional","affiliation":[{"name":"Department of Pathology and Medical Biology, University of Groningen University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerjan J","family":"Navis","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Nephrology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3915-8609","authenticated-orcid":false,"given":"Sanne J","family":"Gordijn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marieke C","family":"Bolling","sequence":"additional","affiliation":[{"name":"Department of Dermatology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard","family":"Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriaan A","family":"Voors","sequence":"additional","affiliation":[{"name":"Department of Cardiology, University Medical Center Groningen University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert DME","family":"Osterhaus","sequence":"additional","affiliation":[{"name":"Research Center for Emerging Infections and Zoonoses University of Veterinary Medicine  Hannover 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