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Vitamin D (VitD) can upregulate ACE2 and has an antagonistic effect on Renin, which exerts a vasodilatation and anti\u2010inflammatory effect against coronavirus disease (COVID\u201019). However, it may also facilitate viral entry by increasing ACE2 as the main SARS\u2010CoV\u20102 receptor and mediates ROS production through NADPH oxidase, as a double\u2010edged sword effect. Lung function and the immune system are also influenced by VitD through several mechanisms, including increased natural antibiotics (Defensin and Cathelicidin) and upregulated transforming growth factor\u2010\u03b2. A higher IgA, Th2\/Th1 ratio, and T\u2010regulatory cells are attributable to VitD effects on the immune cells, while these changes may also be a double\u2010edged sword in COVID\u201019. Although VitD supplementation might be highly recommended in COVID\u201019, the administration's dosage and route could be challenging. Furthermore, this issue has not been mentioned in various studies so far. So, the report aimed to explain the current challenges with the application of VitD in COVID\u201019.<\/jats:p>","DOI":"10.1002\/cbin.11469","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T18:58:12Z","timestamp":1601405892000},"page":"54-57","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["The possible double\u2010edged sword effects of vitamin D on COVID\u201019: A hypothesis"],"prefix":"10.1002","volume":"45","author":[{"given":"Ehsan","family":"Shojaeefar","sequence":"first","affiliation":[{"name":"Immunology Board for Transplantation and Advanced Cellular Therapeutics (ImmunoTACT) Universal Scientific and Education Network (USERN) Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narges","family":"Malih","sequence":"additional","affiliation":[{"name":"Social Determinants of Health Research Center Shahid Beheshti University of Medical Sciences 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