{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:04:17Z","timestamp":1772118257689,"version":"3.50.1"},"reference-count":120,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Angiotensin-Converting Enzyme 2 (ACE2) has been proved to be the main host cell receptor for the binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the COVID-19 pandemic. The SARS-CoV-2 spike (S) protein binds to ACE2 to initiate the process of replication. This enzyme is widely present in human organ tissues, such as the heart and lung. The pathophysiology of ACE2 in SARS-CoV-2 infection is complex and may be associated with several factors and conditions that are more severe in COVID-19 patients, such as age, male gender, and comorbidities, namely, cardiovascular diseases, chronic respiratory diseases, obesity, and diabetes. Here we present a comprehensive review that aims to correlate the levels of expression of the ACE2 in patients with comorbidities and with a poor outcome in COVID-19 disease. Significantly higher levels of expression of ACE2 were observed in myocardial and lung tissues in heart failure and COPD patients, respectively. An age-dependent increase in SARS2-CoV-2 receptors in the respiratory epithelium may be also responsible for the increased severity of COVID-19 lung disease in elderly people. Although the role of ACE2 is highlighted regarding the damage that can arise upon the SARS-CoV-2 invasion, there was no association observed between renin-angiotensin-aldosterone system (RAAS) inhibitors and the severity of COVID-19.<\/jats:p>","DOI":"10.3390\/microorganisms9081692","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T09:03:53Z","timestamp":1628499833000},"page":"1692","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["The Impact of Angiotensin-Converting Enzyme 2 (ACE2) Expression Levels in Patients with Comorbidities on COVID-19 Severity: A Comprehensive Review"],"prefix":"10.3390","volume":"9","author":[{"given":"Rui","family":"Rodrigues","sequence":"first","affiliation":[{"name":"Department of Pathology, Division of Microbiology, Faculty of Medicine, University of Porto, Al. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2899-6615","authenticated-orcid":false,"given":"Sofia","family":"Costa de Oliveira","sequence":"additional","affiliation":[{"name":"Department of Pathology, Division of Microbiology, Faculty of Medicine, University of Porto, Al. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"},{"name":"Center for Research in Health Technologies and Information Systems (CINTESIS), R. Dr. Pl\u00e1cido da Costa, 4200-450 Porto, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1239","DOI":"10.1001\/jama.2020.2648","article-title":"Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and Prevention","volume":"323","author":"Wu","year":"2020","journal-title":"JAMA"},{"key":"ref_2","unstructured":"World Health Organization (2021, April 05). WHO Coronavirus (COVID-19) Dashboard. Available online: https:\/\/covid19.who.int\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1056\/NEJMc2001272","article-title":"Importation and Human-to-Human Transmission of a Novel Coronavirus in Vietnam","volume":"382","author":"Phan","year":"2020","journal-title":"N. Engl. J. 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