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Factors associated with a worse COVID-19 prognosis include old age (&gt;\u200965\u2009years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000\u2009IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04525820\">ClinicalTrials.gov<\/jats:ext-link>\n                      NCT04525820 and SNCTP 2020-01401\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13063-022-06016-2","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T06:13:54Z","timestamp":1643955234000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study\u2014VitCov Trial"],"prefix":"10.1186","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1229-2181","authenticated-orcid":false,"given":"Fabienne","family":"Jaun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Boesing","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"L\u00fcthi-Corridori","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristin","family":"Abig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anja","family":"Makhdoomi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nando","family":"Bloch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Lins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Raess","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victoria","family":"Grillmayr","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philippe","family":"Haas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp","family":"Schuetz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luca","family":"Gabutti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00fcrgen","family":"Muser","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne B.","family":"Leuppi-Taegtmeyer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phanie","family":"Giezendanner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Br\u00e4ndle","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg D.","family":"Leuppi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"6016_CR1","doi-asserted-by":"crossref","unstructured":"Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. 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Geriatr Psychol Neuropsychiatr Vieil. 2016;1:1.","journal-title":"Geriatr Psychol Neuropsychiatr Vieil"}],"container-title":["Trials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06016-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13063-022-06016-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13063-022-06016-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,8]],"date-time":"2022-12-08T18:04:27Z","timestamp":1670522667000},"score":1,"resource":{"primary":{"URL":"https:\/\/trialsjournal.biomedcentral.com\/articles\/10.1186\/s13063-022-06016-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["6016"],"URL":"https:\/\/doi.org\/10.1186\/s13063-022-06016-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-633931\/v1","asserted-by":"object"}]},"ISSN":["1745-6215"],"issn-type":[{"value":"1745-6215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]},"assertion":[{"value":"19 November 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 January 2022","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2022","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Attached to this document is the statement of the Swiss ethics committee (BASEC No: 2020-01401). In this case, several local ethical committees are involved.EKNZ (ethical committee of north-western and central Switzerland) is the lead ethics committee in this trial. Full ethical approval was granted on September 23, 2020.EKOS (ethical committee of eastern Switzerland): The obligation was fulfilled, and we are awaiting the answer and the full approval.CEC TI (ethical committee of Ticino): We are in the process of translating the documents into Italian for submission.Written informed consent will be obtained from all study participants.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate {24}"}},{"value":"No personal data and\/or video of any patient is used in this manuscript; therefore, a consent for publication is not needed.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication {32}"}},{"value":"The authors declare that they have no competing interests.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests {28}"}}],"article-number":"114"}}