{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T06:36:02Z","timestamp":1777444562018,"version":"3.51.4"},"reference-count":62,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2020,6,2]],"date-time":"2020-06-02T00:00:00Z","timestamp":1591056000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Biochem"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:p>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 \u2018lockdown\u2019, 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.<\/jats:p>","DOI":"10.1177\/0004563220928361","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T13:37:34Z","timestamp":1588685854000},"page":"339-350","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Coronavirus disease 2019 (COVID-19)  and the renin-angiotensin system:  A closer look at angiotensin-converting enzyme 2 (ACE2)"],"prefix":"10.1177","volume":"57","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7621-4679","authenticated-orcid":false,"given":"Annalise E","family":"Zemlin","sequence":"first","affiliation":[{"name":"Department of Pathology, Chemical Pathology Division, National Health Laboratory Service (NHLS) and University of Stellenbosch, Tygerberg Hospital, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5937-3686","authenticated-orcid":false,"given":"Owen J","family":"Wiese","sequence":"additional","affiliation":[{"name":"Department of Pathology, Chemical Pathology Division, National Health Laboratory Service (NHLS) and University of Stellenbosch, Tygerberg Hospital, Cape Town, South Africa"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,6,2]]},"reference":[{"key":"bibr1-0004563220928361","unstructured":"Johns Hopkins University & Medicine. COVID-19 Dashboard by the Center for Systems Science and Engineering (CSSE), https:\/\/coronavirus.jhu.edu\/map.html (2020, accessed 27 April 2020)."},{"key":"bibr2-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"bibr3-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"bibr4-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001316"},{"key":"bibr5-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001191"},{"key":"bibr6-0004563220928361","doi-asserted-by":"publisher","DOI":"10.2807\/1560-7917.ES.2020.25.9.2000178"},{"key":"bibr7-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe2001126"},{"key":"bibr8-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30183-5"},{"key":"bibr9-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-018-0296-2"},{"key":"bibr10-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0690-4"},{"key":"bibr11-0004563220928361","doi-asserted-by":"crossref","unstructured":"Lam TT, Shum MH, Zhu HC, et al. Identifying SARS-CoV-2 related coronaviruses in Malayan pangolins.\n                      Nature\n                      . Epub ahead of print 26 March 2020. DOI: 10.1038\/s41586-020-2169-0","DOI":"10.1038\/s41586-020-2169-0"},{"key":"bibr12-0004563220928361","doi-asserted-by":"crossref","unstructured":"Liu PP, Blet A, Smyth D and Li H. The science underlying COVID-19: implications for the cardiovascular system.\n                      Circulation\n                      . Epub ahead of print 15 April 2020. DOI: 10.1161\/CIRCULATIONAHA.120.047549","DOI":"10.1161\/CIRCULATIONAHA.120.047549"},{"key":"bibr13-0004563220928361","doi-asserted-by":"publisher","DOI":"10.3390\/v12040372"},{"key":"bibr14-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2004973"},{"key":"bibr15-0004563220928361","doi-asserted-by":"crossref","unstructured":"Wu Z and McGoogan JM. Characteristics of and important lessons from the coronavirus disease 2019 (COVID-19) outbreak in China: Summary of a report of 72\u2013314 cases from the Chinese center for disease control and prevention.\n                      JAMA\n                      2020; 323(13): 1239\u20131242.","DOI":"10.1001\/jama.2020.2648"},{"key":"bibr16-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc2005073"},{"key":"bibr17-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30211-7"},{"key":"bibr18-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30154-9"},{"key":"bibr19-0004563220928361","doi-asserted-by":"crossref","unstructured":"Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study [published correction appears in Lancet Respir Med. 2020 Apr; 8(4): e26].\n                      Lancet Respir Med\n                      . 2020; 8(5): 475\u2013481.","DOI":"10.1016\/S2213-2600(20)30079-5"},{"key":"bibr20-0004563220928361","doi-asserted-by":"crossref","unstructured":"Ruan Q, Yang K, Wang W, Jiang L, Song J. Clinical predictors of mortality due to COVID-19 based on an analysis of data of 150 patients from Wuhan, China [published correction appears in Intensive Care Med. 6 Apr 2020].\n                      Intensive Care Med\n                      . 2020; 46(5): 846\u2013848.","DOI":"10.1007\/s00134-020-05991-x"},{"key":"bibr21-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)30628-0"},{"key":"bibr22-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2020.1585"},{"key":"bibr23-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1007\/s11427-020-1643-8"},{"key":"bibr24-0004563220928361","doi-asserted-by":"crossref","unstructured":"Arentz M, Yim E, Klaff L, et al. Characteristics and outcomes of 21 critically Ill patients with COVID-19 in Washington state.\n                      JAMA\n                      2020; 323(16): 1612\u20131614.","DOI":"10.1001\/jama.2020.4326"},{"key":"bibr25-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/nature00786"},{"key":"bibr26-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00217.2020"},{"key":"bibr27-0004563220928361","doi-asserted-by":"crossref","first-page":"111","DOI":"10.4172\/2576-1471.1000132","volume":"1","author":"Singh KD","year":"2016","journal-title":"J Cell Signal"},{"key":"bibr28-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/351758"},{"key":"bibr29-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/sj.jhh.1002101"},{"key":"bibr30-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1007\/s10735-010-9264-8"},{"key":"bibr31-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.87.5.e1"},{"key":"bibr32-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/nature02145"},{"key":"bibr33-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2009.02153.x"},{"key":"bibr34-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1002\/path.1570"},{"key":"bibr35-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/s41368-020-0074-x"},{"key":"bibr36-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1042\/CS20200163"},{"key":"bibr37-0004563220928361","doi-asserted-by":"crossref","first-page":"e016219","DOI":"10.1161\/JAHA.120.016219","volume":"9","author":"Guo J","year":"2020","journal-title":"J Am Heart Assoc"},{"key":"bibr38-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1038\/nature03712"},{"key":"bibr39-0004563220928361","doi-asserted-by":"crossref","unstructured":"Patel AB and Verma A. COVID-19 and Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers: what Is the evidence?\n                      JAMA\n                      2020; 323(18): 1769\u20131770.","DOI":"10.1001\/jama.2020.4812"},{"key":"bibr40-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2006.03.001"},{"key":"bibr41-0004563220928361","doi-asserted-by":"crossref","unstructured":"Wang K, Gheblawi M, Oudit GY. Angiotensin converting enzyme 2: a double-edged sword.\n                      Circulation\n                      . Epub ahead of print 26 March 2020. 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Autoimmun Rev 2020;19(6):102536.","DOI":"10.1016\/j.autrev.2020.102536"},{"key":"bibr60-0004563220928361","unstructured":"HFSA\/ACC\/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19, www.acc.org\/latest-in-cardiology\/articles\/2020\/03\/17\/08\/59\/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 (2020, accessed 24 April 2020)."},{"key":"bibr61-0004563220928361","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-020-02862-1"},{"key":"bibr62-0004563220928361","doi-asserted-by":"crossref","unstructured":"Peir\u00f3 C, Moncada S. Substituting Angiotensin-(1-7) to Prevent Lung Damage in SARSCoV2 Infection? Circulation. Epub ahead of print 3 April 2020. 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