{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T13:04:08Z","timestamp":1773666248301,"version":"3.50.1"},"reference-count":107,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T00:00:00Z","timestamp":1656460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fundaci\u00f3n para la investigaci\u00f3n biom\u00e9dica de C\u00f3rdoba (FIBICO)"},{"name":"FAES Farma"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>The COVID-19 pandemic is the greatest challenge facing modern medicine and public health systems. The viral evolution of SARS-CoV-2, with the emergence of new variants with in-creased infectious potential, is a cause for concern. In addition, vaccination coverage remains in-sufficient worldwide. Therefore, there is a need to develop new therapeutic options, and\/or to optimize the repositioning of drugs approved for other indications for COVID-19. This may include the use of calcifediol, the prohormone of the vitamin D endocrine system (VDES) as it may have potential useful effects for the treatment of COVID-19. We review the aspects associating COVID-19 with VDES and the potential use of calcifediol in COVID-19. VDES\/VDR stimulation may enhance innate antiviral effector mechanisms, facilitating the induction of antimicrobial peptides\/autophagy, with a critical modulatory role in the subsequent host reactive hyperinflammatory phase during COVID-19: By decreasing the cytokine\/chemokine storm, regulating the renin\u2013angiotensin\u2013bradykinin system (RAAS), modulating neutrophil activity and maintaining the integrity of the pulmonary epithelial barrier, stimulating epithelial repair, and directly and indirectly decreasing the increased coagulability and prothrombotic tendency associated with severe COVID-19 and its complications. Available evidence suggests that VDES\/VDR stimulation, while maintaining optimal serum 25OHD status, in patients with SARS-CoV-2 infection may significantly reduce the risk of acute respiratory distress syndrome (ARDS) and severe COVID-19, with possible beneficial effects on the need for mechanical ventilation and\/or intensive care unit (ICU) admission, as well as deaths in the course of the disease. The pharmacokinetic and functional characteristics of calcifediol give it superiority in rapidly optimizing 25OHD levels in COVID-19. A pilot study and several observational intervention studies using high doses of calcifediol (0.532 mg on day 1 and 0.266 mg on days 3, 7, 14, 21, and 28) dramatically decreased the need for ICU admission and the mortality rate. We, therefore, propose to use calcifediol at the doses described for the rapid correction of 25OHD deficiency in all patients in the early stages of COVID-19, in association, if necessary, with the new oral antiviral agents.<\/jats:p>","DOI":"10.3390\/nu14132716","type":"journal-article","created":{"date-parts":[[2022,6,29]],"date-time":"2022-06-29T22:43:28Z","timestamp":1656542608000},"page":"2716","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Vitamin D Endocrine System and COVID-19: Treatment with Calcifediol"],"prefix":"10.3390","volume":"14","author":[{"given":"Jose Manuel","family":"Quesada-Gomez","sequence":"first","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8844-0718","authenticated-orcid":false,"given":"Jos\u00e9","family":"Lopez-Miranda","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"},{"name":"Departamento de Medicina Interna, Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"},{"name":"CIBER Fisiopatologia Obesidad y Nutrici\u00f3n (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marta","family":"Entrenas-Castillo","sequence":"additional","affiliation":[{"name":"Hospital Quir\u00f3nSalud, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8520-8278","authenticated-orcid":false,"given":"Antonio","family":"Casado-D\u00edaz","sequence":"additional","affiliation":[{"name":"Instituto Maim\u00f3nides de Investigaci\u00f3n Biom\u00e9dica de C\u00f3rdoba (IMIBIC), Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Unidad de Gesti\u00f3n Cl\u00ednica de Endocrinolog\u00eda y Nutrici\u00f3n, Hospital Universitario Reina Sof\u00eda, 14004 C\u00f3rdoba, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5537-1859","authenticated-orcid":false,"given":"Xavier","family":"Nogues y Solans","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 28029 Madrid, Spain"},{"name":"Internal Medicine Department, IMIM (Hospital del Mar Medical Research Institute), Hospital del Mar, 08003 Barcelona, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8383-9543","authenticated-orcid":false,"given":"Jos\u00e9 Luis","family":"Mansur","sequence":"additional","affiliation":[{"name":"Centro de Endocrinolog\u00eda y Osteoporosis La Plata, Buenos Aires B1902ADQ, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roger","family":"Bouillon","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, Catholic University of Leuven, 3000 Leuven, Belgium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e13868","DOI":"10.1111\/ijcp.13868","article-title":"Novel coronavirus disease (COVID-19) update on epidemiology, pathogenicity, clinical course and treatments","volume":"75","author":"Boban","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_2","unstructured":"Anonim (2022, April 02). COVID Live\u2014Coronavirus Statistics\u2014Worldometer. Available online: https:\/\/www.worldometers.info\/coronavirus\/."},{"key":"ref_3","unstructured":"(2021, July 31). COVID-19 Map\u2014Johns Hopkins Coronavirus Resource Center. Available online: https:\/\/coronavirus.jhu.edu\/map.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41586-021-04352-y","article-title":"Evolution of enhanced innate immune evasion by SARS-CoV-2","volume":"602","author":"Thorne","year":"2022","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1038\/s41586-021-04387-1","article-title":"Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization","volume":"602","author":"Cele","year":"2021","journal-title":"Nature"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"eabj7364","DOI":"10.1126\/science.abj7364","article-title":"Vaccine nationalism and the dynamics and control of SARS-CoV-2","volume":"373","author":"Wagner","year":"2021","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s41392-020-00417-y","article-title":"Drug repurposing for COVID-19 using machine learning and mechanistic models of signal transduction circuits related to SARS-CoV-2 infection","volume":"5","author":"Loucera","year":"2020","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e10576","DOI":"10.1002\/jbm4.10576","article-title":"Vitamin D Endocrine System and COVID-19","volume":"5","author":"Bouillon","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grant, W.B., Lahore, H., McDonnell, S.L., Baggerly, C.A., French, C.B., Aliano, J.L., and Bhattoa, H.P. (2020). Evidence that vitamin d supplementation could reduce risk of influenza and COVID-19 infections and deaths. Nutrients, 12.","DOI":"10.20944\/preprints202003.0235.v2"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"614494","DOI":"10.3389\/fmicb.2021.614494","article-title":"Genomic Feature Analysis of Betacoronavirus Provides Insights Into SARS and COVID-19 Pandemics","volume":"12","author":"Li","year":"2021","journal-title":"Front. Microbiol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/j.chom.2020.02.001","article-title":"Genome Composition and Divergence of the Novel Coronavirus (2019-nCoV) Originating in China","volume":"27","author":"Wu","year":"2020","journal-title":"Cell. Host Microbe"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1007\/s10930-020-09901-4","article-title":"The Proteins of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2 or n-COV19), the Cause of COVID-19","volume":"39","author":"Yoshimoto","year":"2020","journal-title":"Protein J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1016\/j.immuni.2020.07.005","article-title":"Lessons for COVID-19 Immunity from Other Coronavirus Infections","volume":"53","author":"Sariol","year":"2020","journal-title":"Immunity"},{"key":"ref_14","unstructured":"NIH Clinical Spectrum (2022, April 21). Coronavirus Disease 2019 (COVID-19) Treatment Guidelines, Available online: https:\/\/www.covid19treatmentguidelines.nih.gov\/."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1708","DOI":"10.1056\/NEJMoa2002032","article-title":"Clinical Characteristics of Coronavirus Disease 2019 in China","volume":"382","author":"Guan","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1054","DOI":"10.1016\/S0140-6736(20)30566-3","article-title":"Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study","volume":"395","author":"Zhou","year":"2020","journal-title":"Lancet"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"601","DOI":"10.1038\/s41591-021-01283-z","article-title":"Post-acute COVID-19 syndrome","volume":"27","author":"Nalbandian","year":"2021","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced Host Response to SARS-CoV-2 Drives Development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"6854","DOI":"10.1021\/acs.jmedchem.9b00208","article-title":"Vitamin D and its synthetic analogs","volume":"62","author":"Maestro","year":"2019","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1038\/s41430-020-0697-1","article-title":"Vitamin D supplementation: Cholecalciferol, calcifediol, and calcitriol","volume":"74","author":"Vieth","year":"2020","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/bonekey.2013.213","article-title":"History of the discovery of vitamin D and its active metabolites","volume":"3","author":"DeLuca","year":"2014","journal-title":"Bonekey Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"491S","DOI":"10.1093\/ajcn\/88.2.491S","article-title":"From vitamin D to hormone D: Fundamentals of the vitamin D endocrine system essential for good health","volume":"88","author":"Norman","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1056\/NEJMra070553","article-title":"Vitamin D deficiency","volume":"357","author":"Holick","year":"2007","journal-title":"N. Engl. J. Med."},{"key":"ref_24","unstructured":"Bikle, D.D. (2022, April 21). Vitamin D: Production, Metabolism and Mechanisms of Action, Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK278935\/."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e10581","DOI":"10.1002\/jbm4.10581","article-title":"Diagnostic Aspects of Vitamin D: Clinical Utility of Vitamin D Metabolite Profiling","volume":"5","author":"Jones","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_26","unstructured":"Ross, A.C., Taylor, C.L., Yaktine, A.L., and Del Valle, H.B. (2011). Dietary Reference Intakes for Calcium and Vitamin D, National Academies Press."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1210\/jc.2011-0385","article-title":"Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society clinical practice guideline","volume":"96","author":"Holick","year":"2011","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1210\/er.2018-00126","article-title":"Skeletal and Extraskeletal Actions of Vitamin D: Current Evidence and Outstanding Questions","volume":"40","author":"Bouillon","year":"2019","journal-title":"Endocr. Rev."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.mce.2017.04.018","article-title":"Vitamin D endocrinology on the cross-road between immunity and metabolism","volume":"453","author":"Vanherwegen","year":"2017","journal-title":"Mol. Cell. Endocrinol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1210\/endocr\/bqaa218","article-title":"Vitamin D-regulated Gene Expression Profiles: Species-specificity and Cell-specific Effects on Metabolism and Immunity","volume":"162","author":"Dimitrov","year":"2021","journal-title":"Endocrinology"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e10405","DOI":"10.1002\/jbm4.10405","article-title":"Vitamin D and Immune Regulation: Antibacterial, Antiviral, Anti-Inflammatory","volume":"5","author":"Bishop","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e10569","DOI":"10.1002\/jbm4.10569","article-title":"Vitamin D Actions: The Lung Is a Major Target for Vitamin D, FGF23, and Klotho","volume":"5","author":"Janssens","year":"2021","journal-title":"JBMR Plus"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1038\/nrcardio.2016.73","article-title":"Vitamin D and cardiovascular disease prevention","volume":"13","author":"Pilz","year":"2016","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2167","DOI":"10.1007\/s00198-019-05098-0","article-title":"Vitamin D and cardiovascular disorders","volume":"30","author":"Bouillon","year":"2019","journal-title":"Osteoporos. Int."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2421","DOI":"10.1007\/s11010-021-04093-6","article-title":"Role of vitamin D in treating COVID-19-associated coagulopathy: Problems and perspectives","volume":"476","author":"Sengupta","year":"2021","journal-title":"Mol. Cell. Biochem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S2213-2600(21)00218-6","article-title":"The COVID-19 puzzle: Deciphering pathophysiology and phenotypes of a new disease entity","volume":"9","author":"Osuchowski","year":"2021","journal-title":"Lancet Respir. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1017\/S0007114513001840","article-title":"A systematic review of vitamin D status in populations worldwide","volume":"111","author":"Hilger","year":"2014","journal-title":"Br. J. Nutr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.jsbmb.2010.02.021","article-title":"Worldwide status of vitamin D nutrition","volume":"121","author":"Lips","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Bouillon, R., Antonio, L., and Olarte, O.R. (2022). Calcifediol (25OH Vitamin D3) Deficiency: A Risk Factor from Early to Old Age. Nutrients, 14.","DOI":"10.3390\/nu14061168"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s11154-019-09532-w","article-title":"Consensus statement from 2nd International Conference on Controversies in Vitamin D","volume":"21","author":"Giustina","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_41","first-page":"303","article-title":"The relationship between vitamin D status and idiopathic lower-extremity deep vein thrombosis","volume":"7","author":"Khademvatani","year":"2014","journal-title":"Int. J. Gen. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"8570","DOI":"10.1038\/s41598-021-87703-z","article-title":"Evidence of a dysregulated vitamin D endocrine system in SARS-CoV-2 infected patient\u2019s lung cells","volume":"11","author":"George","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"590459","DOI":"10.3389\/fimmu.2020.590459","article-title":"A Network-Based Analysis Reveals the Mechanism Underlying Vitamin D in Suppressing Cytokine Storm and Virus in SARS-CoV-2 Infection","volume":"11","author":"Ahmed","year":"2020","journal-title":"Front. Immunol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1001\/archinternmed.2008.560","article-title":"Association between Serum 25-hydroxyvitamin D level and upper respiratory tract infection in the Third National Health and Nutrition Examination Survey","volume":"169","author":"Ginde","year":"2009","journal-title":"Arch. Intern. Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"4240","DOI":"10.3390\/nu7064240","article-title":"Modulation of the immune response to respiratory viruses by vitamin D","volume":"7","author":"Greiller","year":"2015","journal-title":"Nutrients"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1086\/527488","article-title":"Vitamin D receptor polymorphisms and the risk of acute lower respiratory tract infection in early childhood","volume":"197","author":"Roth","year":"2008","journal-title":"J. Infect. Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"i6583","DOI":"10.1136\/bmj.i6583","article-title":"Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data","volume":"356","author":"Martineau","year":"2017","journal-title":"BMJ"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1016\/S2213-8587(21)00051-6","article-title":"Vitamin D supplementation to prevent acute respiratory infections: A systematic review and meta-analysis of aggregate data from randomised controlled trials","volume":"9","author":"Jolliffe","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/nu12072097","article-title":"Immunologic effects of vitamin d on human health and disease","volume":"12","author":"Charoenngam","year":"2020","journal-title":"Nutrients"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e1909","DOI":"10.1002\/rmv.1909","article-title":"Vitamin D modulation of innate immune responses to respiratory viral infections","volume":"27","author":"Zdrenghea","year":"2017","journal-title":"Rev. Med. Virol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"R133","DOI":"10.1530\/EJE-20-0665","article-title":"MECHANISMS in ENDOCRINOLOGY Vitamin D and COVID-19","volume":"183","author":"Bilezikian","year":"2020","journal-title":"Eur. J. Endocrinol."},{"key":"ref_52","first-page":"267","article-title":"Vitamin D high doses supplementation could represent a promising alternative to prevent or treat COVID-19 infection","volume":"32","author":"Mansur","year":"2020","journal-title":"Clin. E Investig. En Arterioscler."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"105719","DOI":"10.1016\/j.jsbmb.2020.105719","article-title":"Vitamin D receptor stimulation to reduce acute respiratory distress syndrome (ARDS) in patients with coronavirus SARS-CoV-2 infections: Revised Ms SBMB 2020_166","volume":"202","author":"Bouillon","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"104930","DOI":"10.1016\/j.micpath.2021.104930","article-title":"Promising role of defensins peptides as therapeutics to combat against viral infection","volume":"155","author":"Solanki","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.bbrc.2013.06.004","article-title":"Vitamin D upregulates glutamate cysteine ligase and glutathione reductase, and GSH formation, and decreases ROS and MCP-1 and IL-8 secretion in high-glucose exposed U937 monocytes","volume":"437","author":"Jain","year":"2013","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Campbell, G.R., and Spector, S.A. (2012). Vitamin D inhibits human immunodeficiency virus type 1 and Mycobacterium tuberculosis infection in macrophages through the induction of autophagy. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002689"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.chom.2009.08.004","article-title":"Vitamin D3 Induces Autophagy in Human Monocytes\/Macrophages via Cathelicidin","volume":"6","author":"Yuk","year":"2009","journal-title":"Cell. Host Microbe"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1038\/s41586-018-0162-7","article-title":"Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice","volume":"558","author":"Sebti","year":"2018","journal-title":"Nature"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"G208","DOI":"10.1152\/ajpgi.00398.2007","article-title":"Novel role of the vitamin D receptor in maintaining the integrity of the intestinal mucosal barrier","volume":"294","author":"Kong","year":"2007","journal-title":"Am. J. Physiol. \u2014Gastrointest. Liver Physiol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/jid.2011.296","article-title":"Vitamin D receptor activation improves allergen-triggered eczema in mice","volume":"132","author":"Hartmann","year":"2012","journal-title":"J. Invest Dermatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1080\/21688370.2018.1540904","article-title":"Vitamin D Receptor Deletion Leads to the Destruction of Tight and Adherens Junctions in Lungs","volume":"6","author":"Chen","year":"2018","journal-title":"Tissue Barriers"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/s41392-021-00679-0","article-title":"The signal pathways and treatment of cytokine storm in COVID-19","volume":"6","author":"Yang","year":"2021","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3011","DOI":"10.3390\/nu7043011","article-title":"Vitamin D and 1,25(OH)2D regulation of T cells","volume":"7","author":"Cantorna","year":"2015","journal-title":"Nutrients"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.jaut.2017.07.007","article-title":"Modulation of inflammatory and immune responses by vitamin D","volume":"85","author":"Colotta","year":"2017","journal-title":"J. Autoimmun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ki.2008.101","article-title":"Calcium-independent and 1,25(OH)2D3-dependent regulation of the renin-angiotensin system in 1\u03b1-hydroxylase knockout mice","volume":"74","author":"Zhou","year":"2008","journal-title":"Kidney Int."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7432","DOI":"10.3892\/mmr.2017.7546","article-title":"Vitamin D alleviates lipopolysaccharide-induced acute lung injury via regulation of the renin-angiotensin system","volume":"16","author":"Xu","year":"2017","journal-title":"Mol. Med. Rep."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1097\/SHK.0b013e3182a6953e","article-title":"Dysregulated renin-AngioteNsin system contributes to acute lung injury caused by hind-limb ischemia-reperfusion in mice","volume":"40","author":"Chen","year":"2013","journal-title":"Shock"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Mohammad, S., Mishra, A., and Ashraf, M.Z. (2019). Emerging role of vitamin d and its associated molecules in pathways related to pathogenesis of thrombosis. Biomolecules, 9.","DOI":"10.3390\/biom9110649"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"35798","DOI":"10.1074\/jbc.M404865200","article-title":"Disruption of nuclear vitamin D receptor gene causes enhanced thrombogenicity in mice","volume":"279","author":"Aihara","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1096\/fj.15-272872","article-title":"Vitamin D modulates tissue factor and protease-activated receptor 2 expression in vascular smooth muscle cells","volume":"30","author":"Herencia","year":"2016","journal-title":"FASEB J."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"69S","DOI":"10.1177\/1076029618786574","article-title":"Low Vitamin D Levels Are Associated With the Development of Deep Venous Thromboembolic Events in Patients With Ischemic Stroke","volume":"24","author":"Wu","year":"2018","journal-title":"Clin. Appl. Thromb."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3390\/nu9090980","article-title":"1\u03b1, 25-dihydroxyvitamin D3 attenuates TGF-\u03b2-induced pro-fibrotic effects in human lung epithelial cells through inhibition of epithelial-mesenchymal transition","volume":"9","author":"Jiang","year":"2017","journal-title":"Nutrients"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"16525","DOI":"10.1038\/s41598-021-96152-7","article-title":"Vitamin D suppresses bleomycin-induced pulmonary fibrosis by targeting the local renin\u2013angiotensin system in the lung","volume":"11","author":"Chang","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.pupt.2019.01.003","article-title":"Vitamin D prevents experimental lung fibrosis and predicts survival in patients with idiopathic pulmonary fibrosis","volume":"55","author":"Tzilas","year":"2019","journal-title":"Pulm. Pharmacol. Ther."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1080\/10408398.2020.1841090","article-title":"Vitamin D deficiency aggravates COVID-19: Systematic review and meta-analysis","volume":"62","author":"Pereira","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_76","unstructured":"Damascena, A.D., Azevedo, L.M.G., de Oliveira, T.A., da Mota Santana, J., and Pereira, M. (2021). Addendum to vitamin D deficiency aggravates COVID-19: Systematic review and meta-analysis. Crit. Rev. Food Sci. Nutr., 1\u20136."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"145","DOI":"10.5603\/ARM.a2021.0037","article-title":"The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration\u2014A metaanalysis","volume":"89","author":"Oscanoa","year":"2021","journal-title":"Adv. Respir. Med."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"154753","DOI":"10.1016\/j.metabol.2021.154753","article-title":"The link between COVID-19 and VItamin D (VIVID): A systematic review and meta-analysis","volume":"119","author":"Bassatne","year":"2021","journal-title":"Metabolism"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1093\/advances\/nmab012","article-title":"Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis","volume":"12","author":"Kazemi","year":"2021","journal-title":"Adv. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"e2021074","DOI":"10.4178\/epih.e2021074","article-title":"The role of vitamin D deficiency on COVID-19: A systematic review and meta-Analysis of observational studies","volume":"43","author":"Kaya","year":"2021","journal-title":"Epidemiol. Health"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1111\/cen.14540","article-title":"Association of Vitamin D Deficiency with COVID-19 Infection Severity: Systematic Review and Meta-analysis","volume":"96","author":"Wang","year":"2021","journal-title":"Clin. Endocrinol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ijid.2020.12.077","article-title":"Low vitamin D status is associated with coronavirus disease 2019 outcomes: A systematic review and meta-analysis","volume":"104","author":"Liu","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"736665","DOI":"10.3389\/fpubh.2021.736665","article-title":"Vitamin D Status and SARS-CoV-2 Infection and COVID-19 Clinical Outcomes","volume":"9","author":"Chiodini","year":"2021","journal-title":"Front. Public Health"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1484","DOI":"10.1210\/clinem\/dgab892","article-title":"Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis","volume":"107","author":"Dissanayake","year":"2022","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s13054-019-2472-z","article-title":"Trying to identify who may benefit most from future vitamin D intervention trials: A post hoc analysis from the VITDAL-ICU study excluding the early deaths","volume":"23","author":"Martucci","year":"2019","journal-title":"Crit. Care"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Cesareo, R., Falchetti, A., Attanasio, R., Tabacco, G., Naciu, A.M., and Palermo, A. (2019). Hypovitaminosis D: Is it time to consider the use of calcifediol?. Nutrients, 11.","DOI":"10.3390\/nu11051016"},{"key":"ref_87","first-page":"1967","article-title":"Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: A randomized trial","volume":"36","author":"Brandi","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Holick, M.F. (2022). The CO-VID D-Lemma: A Call for Action. Nutrients, 14.","DOI":"10.3390\/nu14050963"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1697","DOI":"10.1007\/s00198-018-4520-y","article-title":"Is calcifediol better than cholecalciferol for vitamin D supplementation?","volume":"29","author":"Bouillon","year":"2018","journal-title":"Osteoporos. Int."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Duchow, E.G., Sibilska-Kaminski, I.K., Plum, L.A., and DeLuca, H.F. (2022). Vitamin D esters are the major form of vitamin D produced by UV irradiation in mice. Photochem. Photobiol. Sci., 1\u20136.","DOI":"10.1007\/s43630-022-00230-2"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1893","DOI":"10.1002\/jbmr.3181","article-title":"Vitamin D-Dependent Rickets Type 1B (25-Hydroxylase Deficiency): A Rare Condition or a Misdiagnosed Condition?","volume":"32","author":"Molin","year":"2017","journal-title":"J. Bone Miner. Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1985","DOI":"10.1002\/jbmr.3884","article-title":"Vitamin D Metabolism Revised: Fall of Dogmas","volume":"34","author":"Bouillon","year":"2019","journal-title":"J. Bone Miner. Res."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/ajcn\/nqab123","article-title":"A pilot-randomized, double-blind crossover trial to evaluate the pharmacokinetics of orally administered 25-hydroxyvitamin D3 and vitamin D3 in healthy adults with differing BMI and in adults with intestinal malabsorption","volume":"114","author":"Charoenngam","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1164\/rccm.201909-1867OC","article-title":"Vitamin d metabolism is dysregulated in asthma and chronic obstructive pulmonary disease","volume":"202","author":"Jolliffe","year":"2020","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1136\/thoraxjnl-2019-213936","article-title":"Effect of vitamin D supplementation on asthma control in patients with vitamin D deficiency: The ACVID randomised clinical trial","volume":"76","year":"2021","journal-title":"Thorax"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/jbmr.551","article-title":"Oral supplementation with 25(OH)D3 versus vitamin D3: Effects on 25(OH)D levels, lower extremity function, blood pressure, and markers of innate immunity","volume":"27","author":"Sidelnikov","year":"2012","journal-title":"J. Bone Miner. Res."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Ai, G., Chen, L., Liu, S., Gong, C., Zhu, X., Zhang, C., Qin, H., Hu, J., and Huang, J. (2021). Associations of immunological features with COVID-19 severity: A systematic review and meta-analysis. BMC Infect. Dis., 21.","DOI":"10.1186\/s12879-021-06457-1"},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Okoye, C., Calsolaro, V., Niccolai, F., Calabrese, A.M., Franchi, R., Rogani, S., Coppini, G., Morelli, V., Caraccio, N., and Monzani, F. (2022). A Randomized, Open-Label Study to Assess Efficacy of Weekly Assumption of Cholecalciferol versus Calcifediol in Older Patients with Hypovitaminosis D. Geriatrics, 7.","DOI":"10.3390\/geriatrics7010013"},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Oristrell, J., Oliva, J.C., Subirana, I., Casado, E., Dom\u00ednguez, D., Toloba, A., Aguilera, P., Esplugues, J., Fafi\u00e1n, P., and Grau, M. (2021). Association of calcitriol supplementation with reduced COVID19 mortality in patients with chronic kidney disease: A population-based study. Biomedicines, 9.","DOI":"10.20944\/preprints202104.0173.v1"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"23380","DOI":"10.1038\/s41598-021-02701-5","article-title":"Real world evidence of calcifediol or vitamin D prescription and mortality rate of COVID-19 in a retrospective cohort of hospitalized Andalusian patients","volume":"11","author":"Loucera","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"105751","DOI":"10.1016\/j.jsbmb.2020.105751","article-title":"Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study","volume":"203","author":"Bouillon","year":"2020","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_102","doi-asserted-by":"crossref","unstructured":"Alcala-diaz, J.F., Limia-perez, L., Gomez-huelgas, R., Martin-escalante, M.D., Cortes-rodriguez, B., Zambrana-garcia, J.L., Entrenas-castillo, M., Perez-caballero, A.I., L\u00f3pez-carmona, M.D., and Garcia-alegria, J. (2021). Calcifediol treatment and hospital mortality due to COVID-19: A cohort study. Nutrients, 13.","DOI":"10.3390\/nu13061760"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"e4017","DOI":"10.1210\/clinem\/dgab405","article-title":"Calcifediol treatment and COVID-19-related outcomes","volume":"106","author":"Nogues","year":"2021","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.eprac.2021.09.016","article-title":"Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Bli","volume":"27","author":"Maghbooli","year":"2021","journal-title":"Endocr. Pract."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"761191","DOI":"10.3389\/fnut.2021.761191","article-title":"Effects of Vitamin D and K on Interleukin-6 in COVID-19","volume":"8","author":"Visser","year":"2022","journal-title":"Front. Nutr."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1080\/07853890.2022.2034936","article-title":"Efficacy and safety of three new oral antiviral treatment (molnupiravir, fluvoxamine and Paxlovid) for COVID-19: A meta-analysis","volume":"54","author":"Wen","year":"2022","journal-title":"Ann. Med."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/joim.13478","article-title":"Advances in the Omicron variant development","volume":"292","author":"Vitiello","year":"2022","journal-title":"J. Intern. Med."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/13\/2716\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:40:36Z","timestamp":1760139636000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/13\/2716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,29]]},"references-count":107,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2022,7]]}},"alternative-id":["nu14132716"],"URL":"https:\/\/doi.org\/10.3390\/nu14132716","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,29]]}}}