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Newer research\nand old experience with other coronaviruses highlighted a probable underlying mechanism\nof disturbance of the renin-angiotensin system (RAS) that is associated with the intrinsic effects of\nSARS-CoV-2 infection.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Objective::<\/jats:title>\n<jats:p>In this review, we aimed to describe the intimate connections between the RAS components,\nthe immune system and COVID-19 pathophysiology.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Methods::<\/jats:title>\n<jats:p>This non-systematic review article summarizes recent evidence on the relationship between\nCOVID-19 and the RAS.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results::<\/jats:title>\n<jats:p>Several studies have indicated that the downregulation of membrane-bound ACE2 may exert\na key role for the impairment of immune functions and for COVID-19 patients\u2019 outcomes. The\ndownregulation may occur by distinct mechanisms, particularly: (1) the shedding process induced\nby the SARS-CoV-2 fusion pathway, which reduces the amount of membrane-bound ACE2, stimulating\nmore shedding by the high levels of Angiotensin II; (2) the endocytosis of ACE2 receptor\nwith the virus itself and (3) by the interferon inhibition caused by SARS-CoV-2 effects on the immune\nsystem, which leads to a reduction of ACE2 receptor expression.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion::<\/jats:title>\n<jats:p>Recent research provides evidence of a reduction of the components of the alternative\nRAS axis, including ACE2 and Angiotensin-(1-7). In contrast, increased levels of Angiotensin II\ncan activate the AT1 receptor in several organs. Consequently, increased inflammation, thrombosis\nand angiogenesis occur in patients infected with SARS-COV-2. Attention should be paid to the interactions\nof the RAS and COVID-19, mainly in the context of novel vaccines and proposed medications.<\/jats:p>\n<\/jats:sec>","DOI":"10.2174\/1389450121666201020154033","type":"journal-article","created":{"date-parts":[[2020,10,21]],"date-time":"2020-10-21T07:29:17Z","timestamp":1603265357000},"page":"254-281","update-policy":"https:\/\/doi.org\/10.2174\/bsp_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Downregulation of Membrane-bound Angiotensin Converting Enzyme 2 (ACE2) Receptor has a Pivotal Role in COVID-19 Immunopathology"],"prefix":"10.2174","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5200-145X","authenticated-orcid":true,"given":"Cristina","family":"Vieira","sequence":"first","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2247-3880","authenticated-orcid":true,"given":"Lucas","family":"Nery","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0209-9935","authenticated-orcid":true,"given":"Ludimila","family":"Martins","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4439-0755","authenticated-orcid":true,"given":"Luiz","family":"Jabour","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3102-5991","authenticated-orcid":true,"given":"Raphael","family":"Dias","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9222-3882","authenticated-orcid":true,"given":"Ana Cristina","family":"Sim\u00f5es e Silva","sequence":"additional","affiliation":[{"name":"Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine, Federal University of Minas Gerais (UFMG), Belo Horizonte, MG, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"965","reference":[{"key":"ref=1","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa2001017","volume":"382","author":"Zhu N.","year":"2020","unstructured":"Zhu N.; Zhang D.; Wang W.; Li X.; Yang B.; Song J.; Zhao X.; Huang B.; Shi W.; Lu R.; Niu P.; Zhan F.; Ma X.; Wang D.; Xu W.; Wu G.; Gao G.F.; Tan W.; A novel coronavirus from patients with pneumonia in China, 2019. 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