Vitamin D Deficiency in COVID-19 Patients and Role of Calcifediol Supplementation

{ 'indexed': {'date-parts': [[2023, 8, 1]], 'date-time': '2023-08-01T04:28:51Z', 'timestamp': 1690864131850}, 'reference-count': 52, 'publisher': 'MDPI AG', 'issue': '15', 'license': [ { 'start': { 'date-parts': [[2023, 7, 30]], 'date-time': '2023-07-30T00:00:00Z', 'timestamp': 1690675200000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, 'abstract': '<jats:p>Hypovitaminosis D has been associated with worse outcome in respiratory tract ' 'infections, with conflicting opinions regarding its role in Coronavirus-19 disease ' '(COVID-19). Our study aimed to evaluate the possible relationship between 25-OH vitamin D ' '(25OHD) values and the following conditions in patients hospitalized for COVID-19: prognosis, ' 'mortality, invasive (IV) and non-invasive (NIV) mechanical ventilation, and orotracheal ' 'intubation (OTI). A further objective was the analysis of a possible positive effect of ' 'supplementation with calcifediol on COVID-19 severity and prognosis. We analyzed 288 patients ' 'hospitalized at the San Giovanni di Dio Hospital in Florence and the Santa Maria alle Scotte ' 'Hospital in Siena, from November 2020 to February 2021. The 25OHD levels correlated ' 'positively with the partial pressure of oxygen and FiO2 (PaO2/FiO2) ratio (r = 0.17; p &lt; ' '0.05). Furthermore, when we analyzed the patients according to the type of respiratory ' 'support, we found that 25OHD levels were markedly reduced in patients who underwent ' 'non-invasive ventilation and orotracheal intubation (OTI). The evaluation of the length of ' 'hospitalization in our population evidenced a longer duration of hospitalization in patients ' 'with severe 25OHD deficiency (&lt;10 ng/mL). Moreover, we found a statistically significant ' 'difference in the mortality rate between patients who had 25OHD levels below 10 ng/mL and ' 'those with levels above this threshold in the total population (50.8% vs. 25.5%, p = 0.005), ' 'as well as between patients with 25OHD levels below 20 ng/mL and those with levels above that ' 'threshold (38.4% vs. 24.6%, p = 0.04). Moreover, COVID-19 patients supplemented with ' 'calcifediol presented a significantly reduced length of hospitalization (p &lt; 0.05). ' 'Interestingly, when we analyzed the possible effects of calcifediol on mortality rate in ' 'patients with COVID-19, we found that the percentage of deaths was significantly higher in ' 'patients who did not receive any supplementation than in those who were treated with ' 'calcifediol (p &lt; 0.05) In conclusion, we have demonstrated with our study the best ' 'prognosis of COVID-19 patients with adequate vitamin D levels and patients treated with ' 'calcifediol supplementation.</jats:p>', 'DOI': '10.3390/nu15153392', 'type': 'journal-article', 'created': {'date-parts': [[2023, 7, 31]], 'date-time': '2023-07-31T05:48:50Z', 'timestamp': 1690782530000}, 'page': '3392', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Vitamin D Deficiency in COVID-19 Patients and Role of Calcifediol Supplementation', 'prefix': '10.3390', 'volume': '15', 'author': [ { 'given': 'Christian', 'family': 'Mingiano', 'sequence': 'first', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Tommaso', 'family': 'Picchioni', 'sequence': 'additional', 'affiliation': [ { 'name': 'Internal Medicine Unit, Ospedale San Giovanni di Dio, 50143 ' 'Florence, Italy'}]}, { 'given': 'Guido', 'family': 'Cavati', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Filippo', 'family': 'Pirrotta', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Marco', 'family': 'Calabrese', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Ranuccio', 'family': 'Nuti', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Stefano', 'family': 'Gonnelli', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Alberto', 'family': 'Fortini', 'sequence': 'additional', 'affiliation': [ { 'name': 'Internal Medicine Unit, Ospedale San Giovanni di Dio, 50143 ' 'Florence, Italy'}]}, { 'given': 'Bruno', 'family': 'Frediani', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'given': 'Luigi', 'family': 'Gennari', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medicine Surgery and Neuroscience, University of ' 'Siena, 53100 Siena, Italy'}]}, { 'ORCID': 'http://orcid.org/0000-0002-3338-6339', 'authenticated-orcid': False, 'given': 'Daniela', 'family': 'Merlotti', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Medical Sciences, Azienda Ospedaliera ' 'Universitaria Senese, 53100 Siena, Italy'}]}], 'member': '1968', 'published-online': {'date-parts': [[2023, 7, 30]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '1199', 'DOI': '10.1056/NEJMoa2001316', 'article-title': 'Early Transmission Dynamics in Wuhan, China, of Novel ' 'Coronavirus-Infected Pneumonia', 'volume': '382', 'author': 'Li', 'year': '2020', 'journal-title': 'N. Engl. J. Med.'}, { 'key': 'ref_2', 'doi-asserted-by': 'crossref', 'first-page': '934', 'DOI': '10.1001/jamainternmed.2020.0994', 'article-title': 'Risk Factors Associated with Acute Respiratory Distress Syndrome and ' 'Death in Patients with Coronavirus Disease 2019 Pneumonia in Wuhan, ' 'China', 'volume': '180', 'author': 'Wu', 'year': '2020', 'journal-title': 'JAMA Intern. Med.'}, { 'key': 'ref_3', '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_4', 'doi-asserted-by': 'crossref', 'first-page': 'e20', 'DOI': '10.1016/S2213-2600(20)30117-X', 'article-title': 'Sex difference and smoking predisposition in patients with COVID-19', 'volume': '8', 'author': 'Cai', 'year': '2020', 'journal-title': 'Lancet Respir. Med.'}, { 'key': 'ref_5', 'doi-asserted-by': 'crossref', 'first-page': '607059', 'DOI': '10.3389/fmed.2021.607059', 'article-title': 'Sex Differences on Clinical Characteristics, Severity, and Mortality in ' 'Adult Patients With COVID-19: A Multicentre Retrospective Study', 'volume': '8', 'author': 'Sha', 'year': '2021', 'journal-title': 'Front. Med.'}, { 'key': 'ref_6', 'doi-asserted-by': 'crossref', 'first-page': '1082', 'DOI': '10.1016/j.jcot.2019.07.004', 'article-title': 'Vitamin D for skeletal and non-skeletal health: What we should know', 'volume': '6', 'author': 'Charoenngam', 'year': '2019', 'journal-title': 'J. Clin. Orthop. Trauma.'}, { 'key': 'ref_7', 'doi-asserted-by': 'crossref', 'first-page': '123', 'DOI': '10.1016/j.abb.2012.04.001', 'article-title': 'Where is the vitamin D receptor?', 'volume': '523', 'author': 'Wang', 'year': '2012', 'journal-title': 'Arch. Biochem. Biophys.'}, { 'key': 'ref_8', 'doi-asserted-by': 'crossref', 'first-page': '543', 'DOI': '10.1016/j.beem.2011.05.010', 'article-title': 'Vitamin D receptor (VDR)-mediated actions of 1α,25(OH)₂vitamin D₃: ' 'Genomic and non-genomic mechanisms', 'volume': '25', 'author': 'Haussler', 'year': '2011', 'journal-title': 'Best. Pract. Res. Clin. Endocrinol. Metab.'}, { 'key': 'ref_9', '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_10', '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_11', 'doi-asserted-by': 'crossref', 'first-page': '1781', 'DOI': '10.1002/eji.201344157', 'article-title': 'Regulation of CYP27B1 and CYP24A1 hydroxylases limits cell-autonomous ' 'activation of vitamin D in dendritic cells', 'volume': '44', 'author': 'Kundu', 'year': '2014', 'journal-title': 'Eur. J. Immunol.'}, { 'key': 'ref_12', 'doi-asserted-by': 'crossref', 'first-page': '1770', 'DOI': '10.1126/science.1123933', 'article-title': 'Toll-like receptor triggering of a vitamin D-mediated human ' 'antimicrobial response', 'volume': '311', 'author': 'Liu', 'year': '2006', 'journal-title': 'Science'}, { 'key': 'ref_13', 'doi-asserted-by': 'crossref', 'unstructured': 'Liu, P.T., Schenk, M., Walker, V.P., Dempsey, P.W., Kanchanapoomi, M., ' 'Wheelwright, M., Vazirnia, A., Zhang, X., Steinmeyer, A., and Zügel, U. ' '(2009). Convergence of IL-1beta and VDR activation pathways in human ' 'TLR2/1-induced antimicrobial responses. PLoS ONE, 4.', 'DOI': '10.1371/journal.pone.0005810'}, { 'key': 'ref_14', 'doi-asserted-by': 'crossref', 'first-page': '363', 'DOI': '10.1139/cjpp-2014-0352', 'article-title': 'An update on the association of vitamin D deficiency with common ' 'infectious diseases', 'volume': '93', 'author': 'Watkins', 'year': '2015', 'journal-title': 'Can. J. Physiol. Pharmacol.'}, { 'key': 'ref_15', 'doi-asserted-by': 'crossref', 'first-page': '1039', 'DOI': '10.1183/09031936.00036709', 'article-title': 'Defective macrophage phagocytosis of bacteria in COPD', 'volume': '35', 'author': 'Taylor', 'year': '2010', 'journal-title': 'Eur. Respir. J.'}, { 'key': 'ref_16', 'doi-asserted-by': 'crossref', 'first-page': '941', 'DOI': '10.1021/pr200724e', 'article-title': 'Differential protein pathways in 1,25-dihydroxyvitamin D3 and ' 'dexamethasone modulated tolerogenic human dendritic cells', 'volume': '11', 'author': 'Ferreira', 'year': '2012', 'journal-title': 'J. Proteome Res.'}, { 'key': 'ref_17', 'doi-asserted-by': 'crossref', 'first-page': '1067', 'DOI': '10.1096/fj.04-3284com', 'article-title': 'Human cathelicidin antimicrobial peptide (CAMP) gene is a direct target ' 'of the vitamin D receptor and is strongly up-regulated in myeloid cells ' 'by 1,25-dihydroxyvitamin D3', 'volume': '19', 'author': 'Gombart', 'year': '2005', 'journal-title': 'FASEB J.'}, { 'key': 'ref_18', 'doi-asserted-by': 'crossref', 'first-page': '1545', 'DOI': '10.1021/acsinfecdis.1c00096', 'article-title': 'Human Cathelicidin Inhibits SARS-CoV-2 Infection: Killing Two Birds ' 'with One Stone', 'volume': '7', 'author': 'Wang', 'year': '2021', 'journal-title': 'ACS Infect. Dis.'}, { 'key': 'ref_19', 'doi-asserted-by': 'crossref', 'first-page': '5155', 'DOI': '10.4049/jimmunol.1200786', 'article-title': 'Availability of 25-hydroxyvitamin D3 to APCs controls the balance ' 'between regulatory and inflammatory T cell responses', 'volume': '189', 'author': 'Jeffery', 'year': '2012', 'journal-title': 'J. Immunol.'}, { 'key': 'ref_20', 'doi-asserted-by': 'crossref', 'first-page': '7', 'DOI': '10.1016/j.imlet.2010.07.002', 'article-title': '1α,25-Dihydroxyvitamin D3 and all-trans retinoic acid synergistically ' 'inhibit the differentiation and expansion of Th17 cells', 'volume': '134', 'author': 'Ikeda', 'year': '2010', 'journal-title': 'Immunol. Lett.'}, { 'key': 'ref_21', 'doi-asserted-by': 'crossref', 'first-page': '997', 'DOI': '10.1074/jbc.M110.163790', 'article-title': 'Lineage-specific effects of 1,25-dihydroxyvitamin D3 on the development ' 'of effector CD4 T cells', 'volume': '286', 'author': 'Palmer', 'year': '2011', 'journal-title': 'J. Biol. Chem.'}, { 'key': 'ref_22', '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_23', 'doi-asserted-by': 'crossref', 'first-page': '1373', 'DOI': '10.1016/j.jiph.2020.06.021', 'article-title': 'Role of vitamin D in preventing of COVID-19 infection, progression and ' 'severity', 'volume': '13', 'author': 'Ali', 'year': '2020', 'journal-title': 'J. Infect. Public Health'}, { 'key': 'ref_24', 'doi-asserted-by': 'crossref', 'first-page': '1664', 'DOI': '10.3389/fimmu.2021.745713', 'article-title': 'Is There a Crucial Link Between Vitamin D Status and Inflammatory ' 'Response in Patients with COVID-19?', 'volume': '12', 'author': 'Saponaro', 'year': '2022', 'journal-title': 'Front. Immunol.'}, { 'key': 'ref_25', 'doi-asserted-by': 'crossref', 'first-page': '19823', 'DOI': '10.1038/s41598-022-21513-9', 'article-title': 'Vitamin D status and severity of COVID-19', 'volume': '12', 'author': 'Nielsen', 'year': '2022', 'journal-title': 'Sci. Rep.'}, { 'key': 'ref_26', 'doi-asserted-by': 'crossref', 'unstructured': 'Nguyen, N.N., Raju, M.N.P., da Graca, B., Wang, D., Mohamed, N.A., ' 'Mutnal, M.B., Rao, A., Bennett, M., Gokingco, M., and Pham, H. (2022). ' '25-hydroxyvitamin D is a predictor of COVID-19 severity of hospitalized ' 'patients. PLoS ONE, 17.', 'DOI': '10.1371/journal.pone.0268038'}, { 'key': 'ref_27', 'first-page': '577', 'article-title': 'Association of 25-Hydroxyvitamin D Level with COVID-19-Related ' 'in-Hospital Mortality: A Retrospective Cohort Study', 'volume': '41', 'year': '2022', 'journal-title': 'J. Am. Nutr. Assoc.'}, { 'key': 'ref_28', 'doi-asserted-by': 'crossref', 'unstructured': 'Davoudi, A., Najafi, N., Aarabi, M., Tayebi, A., Nikaeen, R., Izadyar, ' 'H., Salar, Z., Delavarian, L., Vaseghi, N., and Daftarian, Z. (2021). ' 'Lack of association between vitamin D insufficiency and clinical ' 'outcomes of patients with COVID-19 infection. BMC Infect. Dis., 21.', 'DOI': '10.1186/s12879-021-06168-7'}, { 'key': 'ref_29', '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_30', 'doi-asserted-by': 'crossref', 'first-page': '31', 'DOI': '10.2147/RMHP.S291584', 'article-title': 'Effects of Vitamin D on COVID-19 Infection and Prognosis: A Systematic ' 'Review', 'volume': '14', 'author': 'Yisak', 'year': '2021', 'journal-title': 'Risk Manag. Healthc. Policy'}, { 'key': 'ref_31', '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_32', 'doi-asserted-by': 'crossref', 'first-page': '660420', 'DOI': '10.3389/fnut.2021.660420', 'article-title': 'Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated with ' 'Susceptibility to COVID-19, Severity, and Mortality: A Systematic ' 'Review and Meta-Analysis', 'volume': '8', 'author': 'Akbar', 'year': '2021', 'journal-title': 'Front. Nutr.'}, { 'key': 'ref_33', 'doi-asserted-by': 'crossref', 'first-page': 'e3517', 'DOI': '10.1002/dmrr.3517', 'article-title': 'The effect of vitamin D supplementation on mortality and intensive care ' 'unit admission of COVID-19 patients. A systematic review, meta-analysis ' 'and meta-regression', 'volume': '38', 'author': 'Tentolouris', 'year': '2022', 'journal-title': 'Diabetes Metab. Res. Rev.'}, { 'key': 'ref_34', 'doi-asserted-by': 'crossref', 'first-page': '175', 'DOI': '10.1093/qjmed/hcab009', 'article-title': 'Vitamin D supplementation, COVID-19 and disease severity: A ' 'meta-analysis', 'volume': '114', 'author': 'Shah', 'year': '2021', 'journal-title': 'QJM'}, { 'key': 'ref_35', 'first-page': 'CD015043', 'article-title': 'Vitamin D supplementation for the treatment of COVID-19: A living ' 'systematic review', 'volume': '5', 'author': 'Stroehlein', 'year': '2021', 'journal-title': 'Cochrane Database Syst. Rev.'}, { 'key': 'ref_36', '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_37', '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_38', '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': 'Castillo', 'year': '2020', 'journal-title': 'J. Steroid Biochem. Mol. Biol.'}, { 'key': 'ref_39', 'doi-asserted-by': 'crossref', 'first-page': '111441', 'DOI': '10.1016/j.nut.2021.111441', 'article-title': 'A critical update on the role of mild and serious vitamin D deficiency ' 'prevalence and the COVID-19 epidemic in Europe', 'volume': '93', 'author': 'Bakaloudi', 'year': '2022', 'journal-title': 'Nutrition'}, { 'key': 'ref_40', 'doi-asserted-by': 'crossref', 'first-page': '1006', 'DOI': '10.3945/ajcn.110.008490', 'article-title': 'The relation between acute changes in the systemic inflammatory ' 'response and plasma 25-hydroxyvitamin D concentrations after elective ' 'knee arthroplasty', 'volume': '93', 'author': 'Reid', 'year': '2011', 'journal-title': 'Am. J. Clin. Nutr.'}, { 'key': 'ref_41', 'doi-asserted-by': 'crossref', 'first-page': '154434', 'DOI': '10.1016/j.metabol.2020.154434', 'article-title': 'Letter to the Editor: Vitamin D deficiency in COVID-19: Mixing up cause ' 'and consequence', 'volume': '115', 'author': 'Smolders', 'year': '2021', 'journal-title': 'Metabolism'}, { 'key': 'ref_42', 'doi-asserted-by': 'crossref', 'first-page': '910', 'DOI': '10.3389/fendo.2019.00910', 'article-title': 'Vitamin D Binding Protein: A Historic Overview', 'volume': '10', 'author': 'Bouillon', 'year': '2020', 'journal-title': 'Front. Endocrinol.'}, { 'key': 'ref_43', 'doi-asserted-by': 'crossref', 'first-page': '2992', 'DOI': '10.1002/jmv.26832', 'article-title': 'Vitamin D deficiency is associated with COVID-19 positivity and ' 'severity of the disease', 'volume': '93', 'author': 'Demir', 'year': '2021', 'journal-title': 'J. Med. Virol.'}, { 'key': 'ref_44', 'doi-asserted-by': 'crossref', 'first-page': 'dgz138', 'DOI': '10.1210/clinem/dgz138', 'article-title': 'Preventive Role of Vitamin D Supplementation for Acute Phase Reaction ' 'after Bisphosphonate Infusion in Paget’s Disease', 'volume': '105', 'author': 'Merlotti', 'year': '2020', 'journal-title': 'J. Clin. Endocrinol. Metab.'}, { 'key': 'ref_45', 'doi-asserted-by': 'crossref', 'first-page': '178', 'DOI': '10.1138/20110505', 'article-title': 'Vitamin D and the immune system: Getting it right', 'volume': '8', 'author': 'Mathieu', 'year': '2011', 'journal-title': 'IBMS BoneKey'}, { 'key': 'ref_46', 'doi-asserted-by': 'crossref', 'first-page': '529', 'DOI': '10.1007/s00281-017-0629-x', 'article-title': 'Pathogenic human coronavirus infections: Causes and consequences of ' 'cytokine storm and immunopathology', 'volume': '39', 'author': 'Channappanavar', 'year': '2017', 'journal-title': 'Semin. Immunopathol.'}, { 'key': 'ref_47', 'doi-asserted-by': 'crossref', 'unstructured': 'Campi, I., Gennari, L., Merlotti, D., Mingiano, C., Frosali, A., ' 'Giovanelli, L., Torlasco, C., Pengo, M.F., Heilbron, F., and Soranna, D. ' '(2021). Vitamin D and COVID-19 severity and related mortality: A ' 'prospective study in Italy. BMC Infect. Dis., 21.', 'DOI': '10.1186/s12879-021-06281-7'}, { 'key': 'ref_48', 'doi-asserted-by': 'crossref', 'unstructured': 'Quesada-Gomez, J.M., Lopez-Miranda, J., Entrenas-Castillo, M., ' 'Casado-Díaz, A., Nogues, Y., Solans, X., Mansur, J.L., and Bouillon, R. ' '(2022). Vitamin D Endocrine System and COVID-19: Treatment with ' 'Calcifediol. Nutrients, 14.', 'DOI': '10.3390/nu14132716'}, { 'key': 'ref_49', 'doi-asserted-by': 'crossref', 'unstructured': 'De Niet, S., Trémège, M., Coffiner, M., Rousseau, A.F., Calmes, D., ' 'Frix, A.N., Gester, F., Delvaux, M., Dive, A.F., and Guglielmi, E. ' '(2022). Positive Effects of Vitamin D Supplementation in Patients ' 'Hospitalized for COVID-19: A Randomized, Double-Blind, ' 'Placebo-Controlled Trial. Nutrients, 14.', 'DOI': '10.3390/nu14153048'}, { 'key': 'ref_50', 'doi-asserted-by': 'crossref', 'unstructured': 'Wimalawansa, S.J. (2022). Rapidly Increasing Serum 25(OH)D Boosts the ' 'Immune System, against Infections-Sepsis and COVID-19. Nutrients, 14.', 'DOI': '10.3390/nu14142997'}, { 'key': 'ref_51', '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-Blinded Clinical Trial', 'volume': '27', 'author': 'Maghbooli', 'year': '2022', 'journal-title': 'Endocr. Pract.'}, { 'key': 'ref_52', 'doi-asserted-by': 'crossref', 'unstructured': 'Bičíková, M., Máčová, L., and Hill, M. (2022). Vitamin D as a Possible ' 'COVID-19 Prevention Strategy. Int. J. Mol. Sci., 23.', 'DOI': '10.3390/ijms231810532'}], 'container-title': 'Nutrients', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/15/15/3392/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 7, 31]], 'date-time': '2023-07-31T06:23:46Z', 'timestamp': 1690784626000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/15/15/3392'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 7, 30]]}, 'references-count': 52, 'journal-issue': {'issue': '15', 'published-online': {'date-parts': [[2023, 8]]}}, 'alternative-id': ['nu15153392'], 'URL': 'http://dx.doi.org/10.3390/nu15153392', 'relation': {}, 'ISSN': ['2072-6643'], 'subject': ['Food Science', 'Nutrition and Dietetics'], 'container-title-short': 'Nutrients', 'published': {'date-parts': [[2023, 7, 30]]}}