Vitamin D and Lung Outcomes in Elderly COVID-19 Patients
Alberto Sulli, Emanuele Gotelli, Andrea Casabella, Sabrina Paolino, Carmen Pizzorni, Elisa Alessandri, Marco Grosso, Diego Ferone, Vanessa Smith, Maurizio Cutolo
Nutrients, doi:10.3390/nu13030717
Background and aim: Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate the 25OH-Vitamin D serum concentrations with clinical parameters of lung involvement, in elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five consecutive COVID-19 patients (mean age 76 ± 13 years) and sixtyfive sex-and age-matched control subjects (CNT) were analyzed. The following clinical parameters, including comorbidities, were collected at admission: type of pulmonary involvement, respiratory parameters (PaO 2 , SO 2 , PaCO 2 , PaO 2 /FiO 2 ), laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein). Results: Significantly lower vitamin D serum levels were found in COVID-19 patients than in CNT (median 7.9 vs. 16.3 ng/mL, p = 0.001). Interestingly, a statistically significant positive correlation was observed between vitamin D serum levels and PaO 2 (p = 0.03), SO 2 (p = 0.05), PaO 2 /FiO 2 (p = 0.02), while a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of O 2 in a venturi mask (p = 0.04). A negative correlation was also observed between vitamin D serum levels and severity of radiologic pulmonary involvement, evaluated by computed tomography: in particular, vitamin D was found significantly lower in COVID-19 patients with either multiple lung consolidations (p = 0.0001) or diffuse/severe interstitial lung involvement than in those with mild involvement (p = 0.05). Finally, significantly lower vitamin D serum levels were found in the elderly COVID-19 patients who died during hospitalization, compared to those who survived (median 3.0 vs. 8.4 ng/mL, p = 0.046). Conclusions: This study confirms that 25OH-vitamin D serum deficiency is associated with more severe lung involvement, longer disease duration and risk of death, in elderly COVID-19 patients. The detection of low vitamin D levels also in younger COVID-19 patients with less comorbidities further suggests vitamin D deficiency as crucial risk factor at any age.
Conflicts of Interest: All Authors declare no conflict of interest concerning this manuscript.
References
Adorini, Penna, Control of autoimmune diseases by the vitamin D endocrine system, Nat. Clin. Pract. Rheumatol,
doi:10.1038/ncprheum0855Aibana, Huang, Aboud, Arnedo-Pena, Becerra et al., Vitamin D status and risk of incident tuberculosis disease: A nested case-control study, systematic review, and individual-participant data meta-analysis, PLoS Med,
doi:10.1371/journal.pmed.1002907Berry, Hesketh, Power, Hypponen, Vitamin D status has a linear association with seasonal infections and lung function in British adults, Br. J. Nutr,
doi:10.1017/S0007114511001991Bilezikian, Bikle, Hewison, Lazaretti-Castro, Formenti et al., Mechanisms in Endocrinology: Vitamin D and COVID-19, Eur. J. Endocrinol,
doi:10.1530/EJE-20-0665Bourgonje, Abdulle, Timens, Hillebrands, Navis et al., Angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2 and the pathophysiology of coronavirus disease 2019 (COVID-19), J. Pathol,
doi:10.1002/path.5471Carpagnano, Di Lecce, Quaranta, Zito, Buonamico et al., Vitamin D deficiency as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19, J. Endocrinol. Invest,
doi:10.1007/s40618-020-01370-xCharoenngam, Holick, Immunologic Effects of Vitamin D on Human Health and Disease, Nutrients,
doi:10.3390/nu12072097Cianferotti, Bertoldo, Bischoff-Ferrari, Bruyere, Cooper et al., Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO), Endocrine
Cutolo, Further emergent evidence for the vitamin D endocrine system involvement in autoimmune rheumatic disease risk and prognosis, Ann. Rheum. Dis,
doi:10.1136/annrheumdis-2012-202538Cutolo, Paolino, Sulli, Smith, Pizzorni et al., steroid hormones, and autoimmunity, Ann. N. Y. Acad. Sci,
doi:10.1111/nyas.12432Cutolo, Plebani, Shoenfeld, Adorini, Tincani, Vitamin D endocrine system and the immune response in rheumatic diseases, Vitam. Horm
Dall'ara, Cutolo, Andreoli, Tincani, Paolino, Vitamin D and systemic lupus erythematous: A review of immunological and clinical aspects, Clin. Exp. Rheumatol
Giustina, Formenti, Preventing a covid-19 pandemic Can high prevalence of severe hypovitaminosis D play a role in the high impact of Covid infection in Italy?, BMJ
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin D supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients,
doi:10.3390/nu12040988Grosse, Grosse, Salzer, Dünser, Motz et al., Analysis of cardiopulmonary findings in COVID-19 fatalities: High incidence of pulmonary artery thrombi and acute suppurative bronchopneumonia, Cardiovasc. Pathol,
doi:10.1016/j.carpath.2020.107263Hastie, Mackay, Ho, Celis-Morales, Katikireddi et al., Vitamin D concentrations and COVID-19 infection in UK Biobank Diabetes, Metab. Syndr,
doi:10.1016/j.dsx.2020.04.050Hill, Granic, Davies, Collerton, Martin-Ruiz et al., Serum 25-hydroxyvitamin D concentration and its determinants in the very old: The Newcastle 85+ Study, Osteoporos. Int,
doi:10.1007/s00198-015-3366-9Holick, Binkley, Bischoff-Ferrari, Gordon, Hanley et al., Evaluation, treatment, and prevention of vitamin D deficiency: An Endocrine Society Clinical Practice Guideline, J. Clin. Endocrinol. Metab,
doi:10.1210/jc.2011-0385Im, Je, Baek, Chung, Kwon et al., Nutritional status of patients with coronavirus disease 2019 (COVID-19), Int. J. Infect Dis,
doi:10.1016/j.ijid.2020.08.018Kaminetzky, Moore, Fansiwala, Babb, Kaminetzky et al., Pulmonary Embolism on CTPA in COVID-19 Patients, Radiol. Cardiothorac. Imaging,
doi:10.1148/ryct.2020200308Kommoss, Schwab, Tavernar, Schreck, Wagner et al., The Pathology of Severe COVID-19-Related Lung Damage, Dtsch. Arztebl. Int
Kong, Zhu, Shi, Liu, Chen et al., VDR attenuates acute lung injury by blocking Ang-2-Tie-2 pathway and renin-angiotensin system, Mol. Endocrinol,
doi:10.1210/me.2013-1146Kuba, Imai, Rao, Gao, Guo et al., A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury, Nat. Med,
doi:10.1038/nm1267Kühn, Trotz, Stangl, Prevalence of vitamin D insufficiency and evidence for disease prevention in the older population, Z. Gerontol. Geriatr,
doi:10.1007/s00391-018-1390-zLu, Zhang, Ma, Yue, Zou et al., Link between community-acquired pneumonia and vitamin D levels in older patients, Z. Gerontol. Geriatr,
doi:10.1007/s00391-017-1237-zLu, Zhao, Li, Niu, Yang et al., Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding, Lancet
Machado, Ferro Aissa, Ribeiro, Antunes, Vitamin D supplementation alters the expression of genes associated with hypertension and did not induce DNA damage in rats, J. Toxicol. Environ. Health A,
doi:10.1080/15287394.2019.1592044Malek Mahdavi, A brief review of interplay between vitamin D and angiotensin-converting enzyme 2: Implications for a potential treatment for COVID-19, Rev. Med. Virol,
doi:10.1002/rmv.2119Martineau, Jolliffe, Hooper, Greenberg, Aloia et al., Vitamin D supplementation to prevent acute respiratory tract infections: Systematic review and meta-analysis of individual participant data, BMJ,
doi:10.1136/bmj.i6583Mcgonagle, O'donnell, Sharif, Emery, Bridgewood, Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia, Lancet Rheumatol,
doi:10.1016/S2665-9913(20)30121-1Mohammad, Mishra, Ashraf, Emerging role of vitamin D and its associated molecules in pathways related to pathogenesis of thrombosis, Biomolecules,
doi:10.3390/biom9110649Munshi, Hussein, Toraih, Elshazli, Jardak et al., Vitamin D insufficiency as a potential culprit in critical COVID-19 patients, J. Med. Virol,
doi:10.1002/jmv.26360Orgaz-Molina, Buendia-Eisman, Arrabal-Polo, Ruiz, Arias-Santiago, Deficiency of serum concentration of 25-hydroxyvitamin D in psoriatic patients: A case-control study, J. Am. Acad. Derm,
doi:10.1016/j.jaad.2012.01.040Panagiotou, Tee, Ihsan, Athar, Marchitelli et al., Low serum 25-hydroxyvitamin D (25[OH]D) levels in patients hospitalized with COVID-19 are associated with greater disease severity, Clin. Endocrinol,
doi:10.1111/cen.14276Pereira, Dantas Damascena, Galvão Azevedo, De Almeida Oliveira, Da Mota Santana, Vitamin D deficiency aggravates COVID-19: Systematic review and meta-analysis, Crit. Rev. Food Sci. Nutr,
doi:10.1080/10408398.2020.1841090Phokela, Peleg, Moya, Alcorn, Regulation of human pulmonary surfactant protein gene expression by 1alpha,25-dihydroxyvitamin D3, Am. J. Physiol. Lung Cell Mol. Physiol,
doi:10.1152/ajplung.00129.2004Ranieri, Rubenfeld, Thompson, Ferguson, Caldwell et al., Acute respiratory distress syndrome: The Berlin Definition, JAMA
Rehan, Torday, Peleg, Gennaro, Vouros et al., 1Alpha,25-dihydroxy-3-epi-vitamin D3, a natural metabolite of 1alpha,25dihydroxy vitamin D3: Production and biological activity studies in pulmonary alveolar type II cells, Mol. Genet. Metab,
doi:10.1016/S1096-7192(02)00022-7Rhodes, Subramanian, Laird, Griffin, Kenny, Perspective: Vitamin D deficiency and COVID-19 severityplausibly linked by latitude, ethnicity, impacts on cytokines, ACE2 and thrombosis, J. Intern. Med,
doi:10.1111/joim.13149Sakka, Connors, Hékimian, Martin-Toutain, Crichi et al., Association between D-Dimer levels and mortality in patients with coronavirus disease 2019 (COVID-19): A systematic review and pooled analysis, J. Med. Vasc,
doi:10.1016/j.jdmv.2020.05.003Science, Maguire, Russell, Smieja, Walter et al., Low serum 25-hydroxyvitamin D level and risk of upper respiratory tract infection in children and adolescents, Clin. Infect Dis,
doi:10.1093/cid/cit289Trombetta, Smith, Gotelli, Ghio, Paolino et al., Vitamin D deficiency and clinical correlations in systemic sclerosis patients: A retrospective analysis for possible future developments, PLoS ONE,
doi:10.1371/journal.pone.0179062Vojinovic, Tincani, Sulli, Soldano, Andreoli et al., European multicentre pilot survey to assess vitamin D status in rheumatoid arthritis patients and early development of a new Patient Reported Outcome questionnaire (D-PRO), Autoimmun. Rev,
doi:10.1016/j.autrev.2017.03.002Wang, Koh, Pang, Association between micronutrient deficiency and acute respiratory infections in healthy adults: A systematic review of observational studies, Nutr. J,
doi:10.1186/s12937-019-0507-6Xu, Chen, Wang, Feng, Zhou et al., Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission, Sci. China Life Sci,
doi:10.1007/s11427-020-1637-5Zhou, Yang, Zhang, Li, Liu et al., Clinical Course of 195 Critically ILL COVID-19 Patients, A Retrospective Multi-Center Study, Shock,
doi:10.1097/SHK.0000000000001629DOI record:
{
"DOI": "10.3390/nu13030717",
"ISSN": [
"2072-6643"
],
"URL": "http://dx.doi.org/10.3390/nu13030717",
"abstract": "<jats:p>Background and aim: Vitamin D deficiency is frequently reported in patients with SARS-CoV-2 infection. The aim of this study was to correlate the 25OH-Vitamin D serum concentrations with clinical parameters of lung involvement, in elderly patients hospitalized for SARS-CoV-2 infection. Methods: Sixty-five consecutive COVID-19 patients (mean age 76 ± 13 years) and sixty-five sex- and age-matched control subjects (CNT) were analyzed. The following clinical parameters, including comorbidities, were collected at admission: type of pulmonary involvement, respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein). Results: Significantly lower vitamin D serum levels were found in COVID-19 patients than in CNT (median 7.9 vs. 16.3 ng/mL, p = 0.001). Interestingly, a statistically significant positive correlation was observed between vitamin D serum levels and PaO2 (p = 0.03), SO2 (p = 0.05), PaO2/FiO2 (p = 0.02), while a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p = 0.04), C-reactive protein (p = 0.04) and percentage of O2 in a venturi mask (p = 0.04). A negative correlation was also observed between vitamin D serum levels and severity of radiologic pulmonary involvement, evaluated by computed tomography: in particular, vitamin D was found significantly lower in COVID-19 patients with either multiple lung consolidations (p = 0.0001) or diffuse/severe interstitial lung involvement than in those with mild involvement (p = 0.05). Finally, significantly lower vitamin D serum levels were found in the elderly COVID-19 patients who died during hospitalization, compared to those who survived (median 3.0 vs. 8.4 ng/mL, p = 0.046). Conclusions: This study confirms that 25OH-vitamin D serum deficiency is associated with more severe lung involvement, longer disease duration and risk of death, in elderly COVID-19 patients. The detection of low vitamin D levels also in younger COVID-19 patients with less comorbidities further suggests vitamin D deficiency as crucial risk factor at any age.</jats:p>",
"alternative-id": [
"nu13030717"
],
"author": [
{
"affiliation": [],
"family": "Sulli",
"given": "Alberto",
"sequence": "first"
},
{
"ORCID": "http://orcid.org/0000-0002-4732-0306",
"affiliation": [],
"authenticated-orcid": false,
"family": "Gotelli",
"given": "Emanuele",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Casabella",
"given": "Andrea",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Paolino",
"given": "Sabrina",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Pizzorni",
"given": "Carmen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Alessandri",
"given": "Elisa",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Grosso",
"given": "Marco",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ferone",
"given": "Diego",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Smith",
"given": "Vanessa",
"sequence": "additional"
},
{
"ORCID": "http://orcid.org/0000-0002-5396-0932",
"affiliation": [],
"authenticated-orcid": false,
"family": "Cutolo",
"given": "Maurizio",
"sequence": "additional"
}
],
"container-title": "Nutrients",
"container-title-short": "Nutrients",
"content-domain": {
"crossmark-restriction": false,
"domain": []
},
"created": {
"date-parts": [
[
2021,
2,
25
]
],
"date-time": "2021-02-25T07:36:13Z",
"timestamp": 1614238573000
},
"deposited": {
"date-parts": [
[
2021,
3,
5
]
],
"date-time": "2021-03-05T06:00:40Z",
"timestamp": 1614924040000
},
"indexed": {
"date-parts": [
[
2024,
4,
2
]
],
"date-time": "2024-04-02T15:11:01Z",
"timestamp": 1712070661390
},
"is-referenced-by-count": 58,
"issue": "3",
"issued": {
"date-parts": [
[
2021,
2,
24
]
]
},
"journal-issue": {
"issue": "3",
"published-online": {
"date-parts": [
[
2021,
3
]
]
}
},
"language": "en",
"license": [
{
"URL": "https://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2021,
2,
24
]
],
"date-time": "2021-02-24T00:00:00Z",
"timestamp": 1614124800000
}
}
],
"link": [
{
"URL": "https://www.mdpi.com/2072-6643/13/3/717/pdf",
"content-type": "unspecified",
"content-version": "vor",
"intended-application": "similarity-checking"
}
],
"member": "1968",
"original-title": [],
"page": "717",
"prefix": "10.3390",
"published": {
"date-parts": [
[
2021,
2,
24
]
]
},
"published-online": {
"date-parts": [
[
2021,
2,
24
]
]
},
"publisher": "MDPI AG",
"reference": [
{
"DOI": "10.1016/j.autrev.2011.08.003",
"doi-asserted-by": "publisher",
"key": "ref1"
},
{
"DOI": "10.1016/B978-0-12-386960-9.00014-9",
"article-title": "Vitamin D endocrine system and the immune response in rheumatic diseases",
"author": "Cutolo",
"doi-asserted-by": "crossref",
"first-page": "327",
"journal-title": "Vitam. Horm.",
"key": "ref2",
"volume": "86",
"year": "2011"
},
{
"DOI": "10.1038/ncprheum0855",
"doi-asserted-by": "publisher",
"key": "ref3"
},
{
"article-title": "Vitamin D and systemic lupus erythematous: A review of immunological and clinical aspects",
"author": "Dall’Ara",
"first-page": "153",
"journal-title": "Clin. Exp. Rheumatol.",
"key": "ref4",
"volume": "36",
"year": "2018"
},
{
"DOI": "10.1111/nyas.12432",
"doi-asserted-by": "publisher",
"key": "ref5"
},
{
"DOI": "10.1186/s40001-016-0208-y",
"doi-asserted-by": "publisher",
"key": "ref6"
},
{
"DOI": "10.7861/clinmed.2020-0301",
"doi-asserted-by": "publisher",
"key": "ref7"
},
{
"DOI": "10.1002/jmv.26360",
"doi-asserted-by": "publisher",
"key": "ref8"
},
{
"DOI": "10.1210/jc.2011-0385",
"doi-asserted-by": "publisher",
"key": "ref9"
},
{
"DOI": "10.1530/EJE-20-0665",
"doi-asserted-by": "publisher",
"key": "ref10"
},
{
"DOI": "10.1016/j.autrev.2017.03.002",
"doi-asserted-by": "publisher",
"key": "ref11"
},
{
"DOI": "10.1136/annrheumdis-2012-202538",
"doi-asserted-by": "publisher",
"key": "ref12"
},
{
"DOI": "10.1016/j.jaad.2012.01.040",
"doi-asserted-by": "publisher",
"key": "ref13"
},
{
"DOI": "10.1371/journal.pone.0179062",
"doi-asserted-by": "publisher",
"key": "ref14"
},
{
"DOI": "10.3390/nu12072097",
"doi-asserted-by": "publisher",
"key": "ref15"
},
{
"DOI": "10.1093/cid/cit289",
"doi-asserted-by": "publisher",
"key": "ref16"
},
{
"DOI": "10.1017/S0007114511001991",
"doi-asserted-by": "publisher",
"key": "ref17"
},
{
"DOI": "10.1007/s00391-017-1237-z",
"doi-asserted-by": "publisher",
"key": "ref18"
},
{
"DOI": "10.1371/journal.pmed.1002907",
"doi-asserted-by": "publisher",
"key": "ref19"
},
{
"DOI": "10.1186/s12937-019-0507-6",
"doi-asserted-by": "publisher",
"key": "ref20"
},
{
"DOI": "10.1136/bmj.i6583",
"doi-asserted-by": "publisher",
"key": "ref21"
},
{
"DOI": "10.1016/j.ijid.2020.08.018",
"doi-asserted-by": "publisher",
"key": "ref22"
},
{
"article-title": "Preventing a covid-19 pandemic Can high prevalence of severe hypovitaminosis D play a role in the high impact of Covid infection in Italy?",
"author": "Giustina",
"first-page": "m810",
"journal-title": "BMJ",
"key": "ref23",
"volume": "368",
"year": "2020"
},
{
"DOI": "10.1016/S2213-8587(20)30183-2",
"doi-asserted-by": "publisher",
"key": "ref24"
},
{
"DOI": "10.1016/j.dsx.2020.04.050",
"doi-asserted-by": "publisher",
"key": "ref25"
},
{
"DOI": "10.1111/cen.14276",
"doi-asserted-by": "publisher",
"key": "ref26"
},
{
"DOI": "10.1111/joim.13149",
"doi-asserted-by": "publisher",
"key": "ref27"
},
{
"DOI": "10.1007/s00391-018-1390-z",
"doi-asserted-by": "publisher",
"key": "ref28"
},
{
"DOI": "10.1007/s00198-015-3366-9",
"doi-asserted-by": "publisher",
"key": "ref29"
},
{
"article-title": "Acute respiratory distress syndrome: The Berlin Definition",
"author": "Ranieri",
"first-page": "2526",
"journal-title": "JAMA",
"key": "ref30",
"volume": "307",
"year": "2012"
},
{
"DOI": "10.1378/chest.125.6.2053",
"doi-asserted-by": "publisher",
"key": "ref31"
},
{
"DOI": "10.1097/SHK.0000000000001629",
"doi-asserted-by": "publisher",
"key": "ref32"
},
{
"DOI": "10.1007/s40618-020-01370-x",
"doi-asserted-by": "publisher",
"key": "ref33"
},
{
"DOI": "10.1016/j.jcv.2010.12.006",
"doi-asserted-by": "publisher",
"key": "ref34"
},
{
"DOI": "10.1002/rmv.2119",
"doi-asserted-by": "publisher",
"key": "ref35"
},
{
"DOI": "10.1007/s11427-020-1637-5",
"doi-asserted-by": "publisher",
"key": "ref36"
},
{
"DOI": "10.1016/j.bbrc.2020.02.071",
"doi-asserted-by": "publisher",
"key": "ref37"
},
{
"DOI": "10.1016/S0140-6736(20)30251-8",
"doi-asserted-by": "publisher",
"key": "ref38"
},
{
"DOI": "10.1038/nm1267",
"doi-asserted-by": "publisher",
"key": "ref39"
},
{
"DOI": "10.2310/JIM.0b013e31820ee448",
"doi-asserted-by": "publisher",
"key": "ref40"
},
{
"DOI": "10.1080/15287394.2019.1592044",
"doi-asserted-by": "publisher",
"key": "ref41"
},
{
"DOI": "10.1002/path.5471",
"doi-asserted-by": "publisher",
"key": "ref42"
},
{
"DOI": "10.1210/me.2013-1146",
"doi-asserted-by": "publisher",
"key": "ref43"
},
{
"DOI": "10.1152/ajplung.00126.2020",
"doi-asserted-by": "publisher",
"key": "ref44"
},
{
"DOI": "10.1016/S1096-7192(02)00022-7",
"doi-asserted-by": "publisher",
"key": "ref45"
},
{
"DOI": "10.1152/ajplung.00129.2004",
"doi-asserted-by": "publisher",
"key": "ref46"
},
{
"DOI": "10.1186/s12931-016-0362-3",
"doi-asserted-by": "publisher",
"key": "ref47"
},
{
"DOI": "10.3390/nu12020575",
"doi-asserted-by": "publisher",
"key": "ref48"
},
{
"DOI": "10.3390/biom9110649",
"doi-asserted-by": "publisher",
"key": "ref49"
},
{
"article-title": "The Pathology of Severe COVID-19-Related Lung Damage",
"author": "Kommoss",
"first-page": "500",
"journal-title": "Dtsch. Arztebl. Int.",
"key": "ref50",
"volume": "117",
"year": "2020"
},
{
"DOI": "10.1016/S2665-9913(20)30121-1",
"doi-asserted-by": "publisher",
"key": "ref51"
},
{
"DOI": "10.1182/blood-2008-06-165845",
"doi-asserted-by": "publisher",
"key": "ref52"
},
{
"DOI": "10.1016/j.jdmv.2020.05.003",
"doi-asserted-by": "publisher",
"key": "ref53"
},
{
"DOI": "10.1136/postgradmedj-2020-138712",
"doi-asserted-by": "publisher",
"key": "ref54"
},
{
"DOI": "10.1136/rmdopen-2020-001454",
"doi-asserted-by": "publisher",
"key": "ref55"
},
{
"DOI": "10.3390/nu10111656",
"doi-asserted-by": "publisher",
"key": "ref56"
},
{
"DOI": "10.1136/jclinpath-2012-201301",
"doi-asserted-by": "publisher",
"key": "ref57"
},
{
"DOI": "10.1097/MJT.0000000000001222",
"doi-asserted-by": "publisher",
"key": "ref58"
},
{
"DOI": "10.1148/ryct.2020200308",
"doi-asserted-by": "publisher",
"key": "ref59"
},
{
"DOI": "10.1016/j.carpath.2020.107263",
"doi-asserted-by": "publisher",
"key": "ref60"
},
{
"DOI": "10.3390/nu12040988",
"doi-asserted-by": "publisher",
"key": "ref61"
},
{
"DOI": "10.1007/s12020-017-1290-9",
"article-title": "Vitamin D supplementation in the prevention and management of major chronic diseases not related to mineral homeostasis in adults: Research for evidence and a scientific statement from the European society for clinical and economic aspects of osteoporosis and osteoarthritis (ESCEO)",
"author": "Cianferotti",
"doi-asserted-by": "crossref",
"first-page": "245",
"journal-title": "Endocrine",
"key": "ref62",
"volume": "56",
"year": "2017"
},
{
"DOI": "10.1080/10408398.2020.1841090",
"doi-asserted-by": "publisher",
"key": "ref63"
}
],
"reference-count": 63,
"references-count": 63,
"relation": {},
"resource": {
"primary": {
"URL": "https://www.mdpi.com/2072-6643/13/3/717"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"subject": [
"Food Science",
"Nutrition and Dietetics"
],
"subtitle": [],
"title": "Vitamin D and Lung Outcomes in Elderly COVID-19 Patients",
"type": "journal-article",
"volume": "13"
}
