The Relationship Between Vitamin D Status and the Clinical Severity of COVID-19 Infection: A Retrospective Single-Center Analysis
Christiana Zidrou, Angelo V Vasiliadis, Maria Tsatlidou, Maria Sentona, Stavros Vogiatzis, Anastasios Beletsiotis
Cureus, doi:10.7759/cureus.22385
Background and objective Some studies have suggested a potential protective role of vitamin D in coronavirus disease 2019 patients, and this has led to a debate on the topic in the medical community. However, the reported data on the number of hospitalized patients who were vitamin D-deficient is not convincing. In light of this, the aim of the present study was to explore if vitamin D deficiency is correlated with severity and mortality rates of COVID-19 infection in hospitalized COVID-19 patients at a tertiary care hospital in Greece.
Methods We conducted a single-center retrospective study involving 71 patients hospitalized with COVID-19 from August to October 2020. Serum 25-hydroxyvitamin D (25(OH)D) level was assessed in all patients within 48 hours of hospital admission. Serum 25(OH)D level ≤20 ng/ml was defined as a deficiency, while that >20 ng/ml as repletion. The primary outcomes of the infection were classified as partial/complete recovery and mortality during hospitalization. The secondary outcomes were blood markers of inflammation and thrombosis.
Results Among the 71 COVID-19-positive patients [mean age: 63 years, range: 20-97; male (n=47; 66.2%): female (n=24; 33.8%)] who were enrolled in the study, 46 (64.8%) patients had 25(OH)D levels ≤20 ng/ml and 25 (35.2%) had a level >20 ng/ml. According to the patients' medical history, 55 patients (77.5%) had comorbidities. It appears that vitamin D deficiency (<20 ng/ml) significantly correlated with elevated biochemical markers such as procalcitonin and troponin (p<0.001). Moreover, male gender, advanced age (>60 years), and comorbidities were positively associated with more severe COVID-19 infection (elevated inflammation markers, radiographic findings on X-rays, and increased length of hospital stay).
Conclusion These preliminary findings show that vitamin D status among the patients was not related to the severity of COVID-19 infection.
Additional Information Disclosures Human subjects: Consent was obtained or waived by all participants in this study. Hospital Ethics Committee, General Hospital of Thessaloniki "Papageorgiou" issued approval 345/April 2021. This study has been approved by the Hospital Ethics Committee at the General Hospital of Thessaloniki "Papageorgiou". Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue.
Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.
References
Lagadinou, Zorbas, Velissaris, Vitamin D plasma levels in patients with COVID-19: a case series, Infez Med
Raharusuna, Priambada, Budiarti, Agung, Budi, Patterns of COVID-19 mortality and vitamin D: an Indonesian study
Readcube, None
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"DOI": "10.1016/S0140-6736(20)30211-7",
"article-title": "Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study",
"author": "Chen N",
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"volume": "395",
"year": "2020"
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"DOI": "10.1016/j.ijid.2020.03.017",
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"key": "ref2",
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"volume": "94",
"year": "2020"
},
{
"DOI": "10.1186/s13054-020-2833-7",
"article-title": "Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan",
"author": "Shi Y",
"doi-asserted-by": "publisher",
"journal-title": "Crit Care",
"key": "ref3",
"unstructured": "Shi Y, Yu X, Zhao H, Wang H, Zhao R, Sheng J. Host susceptibility to severe COVID-19 and establishment of a host risk score: findings of 487 cases outside Wuhan. Crit Care. 2020, 24:108. 10.1186/s13054-020-2833-7",
"volume": "24",
"year": "2020"
},
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"DOI": "10.1101/2020.05.08.20095893",
"article-title": "Association of vitamin d deficiency and treatment with COVID-19 incidence [PREPRINT]",
"author": "Meltzer DO",
"doi-asserted-by": "publisher",
"journal-title": "medRxiv",
"key": "ref4",
"unstructured": "Meltzer DO, Best TJ, Zhang H, Vokes T, Arora V, Solway J. Association of vitamin d deficiency and treatment with COVID-19 incidence [PREPRINT]. medRxiv. 2020, 10.1101/2020.05.08.20095893",
"year": "2020"
},
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"DOI": "10.3390/nu12092775.25",
"article-title": "Impact of vitamin D deficiency on COVID-19—a prospective analysis from the CovILD Registry",
"author": "Pizzini A",
"doi-asserted-by": "publisher",
"journal-title": "Nutrients",
"key": "ref5",
"unstructured": "Pizzini A, Aichner M, Sahanic S, et al.. Impact of vitamin D deficiency on COVID-19—a prospective analysis from the CovILD Registry. Nutrients. 2020, 12:2775. 10.3390/nu12092775.25",
"volume": "12",
"year": "2020"
},
{
"DOI": "10.1136/postgradmedj-2020-138712",
"article-title": "Vitamin D status and outcomes for hospitalised older patients with COVID-19",
"author": "Baktash V",
"doi-asserted-by": "publisher",
"journal-title": "Postgrad Med J",
"key": "ref6",
"unstructured": "Baktash V, Hosack T, Patel N, et al.. Vitamin D status and outcomes for hospitalised older patients with COVID-19. Postgrad Med J. 2021, 97:442-7. 10.1136/postgradmedj-2020-138712",
"volume": "97",
"year": "2021"
},
{
"DOI": "10.1007/s00394-020-02411-0",
"article-title": "Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study",
"author": "Abrishami A",
"doi-asserted-by": "publisher",
"journal-title": "Eur J Nutr",
"key": "ref7",
"unstructured": "Abrishami A, Dalili N, Mohammadi Torbati P, Asgari R, Arab-Ahmadi M, Behnam B, Sanei-Taheri M. Possible association of vitamin D status with lung involvement and outcome in patients with COVID-19: a retrospective study. Eur J Nutr. 2021, 60:2249-57. 10.1007/s00394-020-02411-0",
"volume": "60",
"year": "2021"
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"DOI": "10.4158/EP161604.RA",
"article-title": "Vitamin D binding protein and 25-hydroxyvitamin D levels: emerging clinical applications",
"author": "Jassil NK",
"doi-asserted-by": "publisher",
"journal-title": "Endocr Pract",
"key": "ref8",
"unstructured": "Jassil NK, Sharma A, Bikle D, Wang X. Vitamin D binding protein and 25-hydroxyvitamin D levels: emerging clinical applications. Endocr Pract. 2017, 23:605-13. 10.4158/EP161604.RA",
"volume": "23",
"year": "2017"
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"DOI": "10.1101/2020.04.08.20058578",
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"journal-title": "medRxiv",
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"year": "2020"
},
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"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",
"author": "Martineau AR",
"doi-asserted-by": "publisher",
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"key": "ref10",
"unstructured": "Martineau AR, Jolliffe DA, Hooper RL, et al.. Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data. BMJ. 2017, 356:i6583. 10.1136/bmj. i6583",
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"doi-asserted-by": "publisher",
"journal-title": "Aging Clin Exp Res",
"key": "ref11",
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"year": "2020"
},
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"DOI": "10.1152/ajpendo.00138.2020",
"article-title": "COVID-19 and vitamin D-is there a link and an opportunity for intervention?",
"author": "Jakovac H",
"doi-asserted-by": "publisher",
"journal-title": "Am J Physiol Endocrinol Metab",
"key": "ref12",
"unstructured": "Jakovac H. COVID-19 and vitamin D-is there a link and an opportunity for intervention?. Am J Physiol Endocrinol Metab. 2020, 318:E589. 10.1152/ajpendo.00138.2020",
"volume": "318",
"year": "2020"
},
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"DOI": "10.3389/fimmu.2020.01523",
"article-title": "Vitamin D supplementation: a potential approach for coronavirus/COVID-19 therapeutics?",
"author": "Arboleda JF",
"doi-asserted-by": "publisher",
"journal-title": "Front Immunol",
"key": "ref13",
"unstructured": "Arboleda JF, Urcuqui-Inchima S. Vitamin D supplementation: a potential approach for coronavirus/COVID-19 therapeutics?. Front Immunol. 2020, 11:1523. 10.3389/fimmu.2020.01523",
"volume": "11",
"year": "2020"
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"article-title": "Vitamin D status: measurement, interpretation, and clinical application",
"author": "Holick MF",
"doi-asserted-by": "publisher",
"journal-title": "Ann Epidemiol",
"key": "ref14",
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"volume": "19",
"year": "2009"
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"volume": "47",
"year": "2022"
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"DOI": "10.1016/S2213-8587(20)30268-0",
"article-title": "Vitamin D for COVID-19: a case to answer?",
"author": "Martineau AR",
"doi-asserted-by": "publisher",
"journal-title": "Lancet Diabetes Endocrinol",
"key": "ref16",
"unstructured": "Martineau AR, Forouhi NG. Vitamin D for COVID-19: a case to answer?. Lancet Diabetes Endocrinol. 2020, 8:735-6. 10.1016/S2213-8587(20)30268-0",
"volume": "8",
"year": "2020"
},
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"DOI": "10.1038/s41598-021-85809-y",
"article-title": "Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19",
"author": "Jevalikar G",
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"journal-title": "Sci Rep",
"key": "ref17",
"unstructured": "Jevalikar G, Mithal A, Singh A, et al.. Lack of association of baseline 25-hydroxyvitamin D levels with disease severity and mortality in Indian patients hospitalized for COVID-19. Sci Rep. 2021, 11:6258. 10.1038/s41598-021-85809-y",
"volume": "11",
"year": "2021"
},
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"DOI": "10.1186/s12879-021-06281-7",
"article-title": "Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy",
"author": "Campi I",
"doi-asserted-by": "publisher",
"journal-title": "BMC Infect Dis",
"key": "ref18",
"unstructured": "Campi I, Gennari L, Merlotti D, et al.. Vitamin D and COVID-19 severity and related mortality: a prospective study in Italy. BMC Infect Dis. 2021, 21:566. 10.1186/s12879-021-06281-7",
"volume": "21",
"year": "2021"
},
{
"DOI": "10.3390/nu13114047",
"article-title": "Rapid and effective vitamin D supplementation may present better clinical outcomes in COVID-19 (SARS-CoV-2) patients by altering serum INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1",
"author": "Gönen MS",
"doi-asserted-by": "publisher",
"journal-title": "Nutrients",
"key": "ref19",
"unstructured": "Gönen MS, Alaylıoğlu M, Durcan E, et al.. Rapid and effective vitamin D supplementation may present better clinical outcomes in COVID-19 (SARS-CoV-2) patients by altering serum INOS1, IL1B, IFNg, cathelicidin-LL37, and ICAM1. Nutrients. 2021, 13:4047. 10.3390/nu13114047",
"volume": "13",
"year": "2021"
},
{
"article-title": "Patterns of COVID-19 mortality and vitamin D: an Indonesian study [PREPRINT]",
"author": "Raharusuna P",
"journal-title": "Readcube",
"key": "ref20",
"unstructured": "Raharusuna P, Priambada S, Budiarti C, Agung E, Budi C. Patterns of COVID-19 mortality and vitamin D: an Indonesian study [PREPRINT]. Readcube. 2020,",
"year": "2020"
},
{
"article-title": "Vitamin D plasma levels in patients with COVID-19: a case series",
"author": "Lagadinou M",
"journal-title": "Infez Med",
"key": "ref21",
"unstructured": "Lagadinou M, Zorbas B, Velissaris D. Vitamin D plasma levels in patients with COVID-19: a case series. Infez Med. 2021, 29:224-8.",
"volume": "29",
"year": "2021"
},
{
"article-title": "Dietary Reference Intakes for Calcium and Vitamin D",
"key": "ref22",
"unstructured": "Dietary Reference Intakes for Calcium and Vitamin D. Ross AC, Taylor CL, Yaktine AL, Del Valle HB (ed). National Academies Press, Washington, DC; 2011.",
"year": "2011"
},
{
"DOI": "10.1056/NEJMsa2011686",
"article-title": "Hospitalization and mortality among black patients and white patients with Covid-19",
"author": "Price-Haywood EG",
"doi-asserted-by": "publisher",
"journal-title": "N Engl J Med",
"key": "ref23",
"unstructured": "Price-Haywood EG, Burton J, Fort D, Seoane L. Hospitalization and mortality among black patients and white patients with Covid-19. N Engl J Med. 2020, 382:2534-43. 10.1056/NEJMsa2011686",
"volume": "382",
"year": "2020"
},
{
"DOI": "10.1016/j.jinf.2020.04.021",
"article-title": "Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis",
"author": "Zheng Z",
"doi-asserted-by": "publisher",
"journal-title": "J Infect",
"key": "ref24",
"unstructured": "Zheng Z, Peng F, Xu B, et al.. Risk factors of critical & mortal COVID-19 cases: a systematic literature review and meta-analysis. J Infect. 2020, 81:e16-25. 10.1016/j.jinf.2020.04.021",
"volume": "81",
"year": "2020"
},
{
"DOI": "10.1038/s41598-021-97017-9",
"article-title": "The relationship between serum 25-hydroxyvitamin D levels and the severity of COVID-19 disease and its mortality",
"author": "Vasheghani M",
"doi-asserted-by": "publisher",
"journal-title": "Sci Rep",
"key": "ref25",
"unstructured": "Vasheghani M, Jannati N, Baghaei P, Rezaei M, Aliyari R, Marjani M. The relationship between serum 25-hydroxyvitamin D levels and the severity of COVID-19 disease and its mortality. Sci Rep. 2021, 11:17594. 10.1038/s41598-021-97017-9",
"volume": "11",
"year": "2021"
},
{
"DOI": "10.1186/s13293-020-00304-9",
"article-title": "Impact of sex and gender on COVID-19 outcomes in Europe",
"author": "Gebhard C",
"doi-asserted-by": "publisher",
"journal-title": "Biol Sex Differ",
"key": "ref26",
"unstructured": "Gebhard C, Regitz-Zagrosek V, Neuhauser HK, Morgan R, Klein SL. Impact of sex and gender on COVID-19 outcomes in Europe. Biol Sex Differ. 2020, 11:29. 10.1186/s13293-020-00304-9",
"volume": "11",
"year": "2020"
},
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"DOI": "10.1016/j.ajic.2020.06.213",
"article-title": "Prevalence of comorbidities among individuals with COVID-19: a rapid review of current literature",
"author": "Bajgain KT",
"doi-asserted-by": "publisher",
"journal-title": "Am J Infect Control",
"key": "ref27",
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"volume": "49",
"year": "2021"
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"DOI": "10.1016/j.eclinm.2020.100449",
"article-title": "Prognostic factors associated with mortality risk and disease progression in 639 critically ill patients with COVID-19 in Europe: initial report of the international RISC-19-ICU prospective observational cohort",
"author": "Wendel Garcia PD",
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"volume": "25",
"year": "2020"
},
{
"DOI": "10.1001/jama.2020.6775",
"article-title": "Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area",
"author": "Richardson S",
"doi-asserted-by": "publisher",
"journal-title": "JAMA",
"key": "ref29",
"unstructured": "Richardson S, Hirsch JS, Narasimhan M, et al.. Presenting characteristics, comorbidities, and outcomes among 5700 patients hospitalized with COVID-19 in the New York City area. JAMA. 2020, 323:2052-9. 10.1001/jama.2020.6775",
"volume": "323",
"year": "2020"
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"DOI": "10.1017/S0007114519000151",
"article-title": "Prevalence and predictors of vitamin D deficiency in a nationally representative sample of adults participating in the 2011-2013 Australian Health Survey",
"author": "Malacova E",
"doi-asserted-by": "publisher",
"journal-title": "Br J Nutr",
"key": "ref30",
"unstructured": "Malacova E, Cheang PR, Dunlop E, et al.. Prevalence and predictors of vitamin D deficiency in a nationally representative sample of adults participating in the 2011-2013 Australian Health Survey. Br J Nutr. 2019, 121:894-904. 10.1017/S0007114519000151",
"volume": "121",
"year": "2019"
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