The impact of supplementing vitamin D through different methods on the prognosis of COVID-19 patients: a systematic review and meta-analysis
Xiangqun Zhang, Junyuan Wu, Hongmeng Dong, Na Shang, Yixuan Li, Ying Zhang, Shubin Guo, Xue Mei
Frontiers in Nutrition, doi:10.3389/fnut.2024.1441847
Objective: To analyze the impact of different methods of Vitamin D administration on the prognosis of COVID-19 patients. Methods: A comprehensive literature search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled trials and cohort studies that compared Vitamin D supplementation with control groups in COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses were performed based on the dosing regimen (singledose vs. continuous-dose), total Vitamin D intake within 14 days (≥100,000 IU vs. <100,000 IU), and baseline serum Vitamin D levels (deficient group: 25OHD < 30 ng/mL vs. non-restricted group). A random-effects model was employed for meta-analysis to account for heterogeneity among studies. Results: A total of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D supplementation significantly reduced the mortality rate (RR = 0.72, 95% CI: 0.54-0.94, I 2 = 54%, p = 0.02), with continuous dosing being more effective (RR = 0.53, 95% CI: 0.34-0.83, I 2 = 55%, p = 0.006) compared to single-dose (RR = 0.88, 95% CI: 0.69-1.12, I 2 = 21%, p = 0.3), and lower total doses (<100,000 IU) showing greater benefit (RR = 0.30, 95% CI: 0.21-0.44, I 2 = 0%, p < 0.0001). Mortality was significantly reduced in the Vitamin D-deficient group (25OHD < 30 ng/mL) (RR = 0.73, 95% CI: 0.59-0.89, I 2 = 0%, p = 0.002) but not in the non-restricted group. Regarding ICU admission, supplementation reduced ICU admission rates (RR = 0.58, 95% CI: 0.38-0.88, I 2 = 74%, p = 0.01), with continuous dosing (RR = 0.44, 95% CI: 0.22-0.90, I 2 = 74%, p = 0.02) being more effective than single-dose (RR = 0.79, 95% CI: 0.61-1.03, I 2 = 22%, p = 0.08), and lower doses (<100,000 IU) providing more significant reduction (RR = 0.31, 95% CI: 0.21-0.47, I 2 = 0%, p = 0.001). ICU admission rates were significantly reduced in the Vitamin D-deficient group (RR = 0.63, 95% CI: 0.42-0.93, I 2 = 0%, p = 0.02) but not in the non-restricted group (RR = 0.59, 95% CI: 0.32-1.11, I 2 = 86%, p = 0.1). For length of hospital stay, no significant differences were observed between Vitamin D and control groups (MD = -1, 95% CI: -2.16 to 0.16, p = 0.13), and subgroup analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no significant differences. Similarly, for
Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Publisher's note All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.
Supplementary material The Supplementary material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fnut.2024.1441847/ full#supplementary-material Frontiers in Nutrition 21 frontiersin.org
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'abstract': '<jats:sec><jats:title>Objective</jats:title><jats:p>To analyze the impact of different '
'methods of Vitamin D administration on the prognosis of COVID-19 '
'patients.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>A '
'comprehensive literature search was conducted across four databases: PubMed, Embase, Web of '
'Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled '
'trials and cohort studies that compared Vitamin D supplementation with control groups in '
'COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) '
'admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses '
'were performed based on the dosing regimen (single-dose vs. continuous-dose), total Vitamin D '
'intake within 14\u2009days (≥100,000\u2009IU vs. &lt;100,000\u2009IU), and baseline serum '
'Vitamin D levels (deficient group: 25OHD\u2009&lt;\u200930\u2009ng/mL vs. non-restricted '
'group). A random-effects model was employed for meta-analysis to account for heterogeneity '
'among studies.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>A total '
'of 21 studies involving 4,553 participants were included. In terms of mortality, Vitamin D '
'supplementation significantly reduced the mortality rate (RR\u2009=\u20090.72, 95% CI: '
'0.54–0.94, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200954%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.02), with continuous dosing being more effective '
'(RR\u2009=\u20090.53, 95% CI: 0.34–0.83, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> '
'=\u200955%, <jats:italic>p</jats:italic>\u2009=\u20090.006) compared to single-dose (RR\u2009'
'=\u20090.88, 95% CI: 0.69–1.12, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009'
'21%, <jats:italic>p</jats:italic>\u2009=\u20090.3), and lower total doses '
'(&lt;100,000\u2009IU) showing greater benefit (RR\u2009=\u20090.30, 95% CI: 0.21–0.44, '
'<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, '
'<jats:italic>p</jats:italic>\u2009&lt;\u20090.0001). Mortality was significantly reduced '
'in the Vitamin D-deficient group (25OHD\u2009&lt;\u200930\u2009ng/mL) (RR\u2009=\u2009'
'0.73, 95% CI: 0.59–0.89, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.002) but not in the non-restricted group. '
'Regarding ICU admission, supplementation reduced ICU admission rates (RR\u2009=\u20090.58, '
'95% CI: 0.38–0.88, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200974%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.01), with continuous dosing (RR\u2009=\u20090.44, '
'95% CI: 0.22–0.90, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u200974%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.02) being more effective than single-dose (RR\u2009'
'=\u20090.79, 95% CI: 0.61–1.03, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009'
'22%, <jats:italic>p</jats:italic>\u2009=\u20090.08), and lower doses (&lt;100,000\u2009'
'IU) providing more significant reduction (RR\u2009=\u20090.31, 95% CI: 0.21–0.47, '
'<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.001). ICU admission rates were significantly '
'reduced in the Vitamin D-deficient group (RR\u2009=\u20090.63, 95% CI: 0.42–0.93, '
'<jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u20090%, '
'<jats:italic>p</jats:italic>\u2009=\u20090.02) but not in the non-restricted group (RR\u2009'
'=\u20090.59, 95% CI: 0.32–1.11, <jats:italic>I</jats:italic><jats:sup>2</jats:sup> =\u2009'
'86%, <jats:italic>p</jats:italic>\u2009=\u20090.1). For length of hospital stay, no '
'significant differences were observed between Vitamin D and control groups (MD\u2009=\u2009'
'−1, 95% CI: −2.16 to 0.16, <jats:italic>p</jats:italic>\u2009=\u20090.13), and subgroup '
'analyses by dosing regimen, total dose, and baseline Vitamin D levels also showed no '
'significant differences. Similarly, for endotracheal intubation, there was no significant '
'difference in intubation rates between groups (RR\u2009=\u20090.78, 95% CI: 0.56–1.08, '
'<jats:italic>p</jats:italic>\u2009=\u20090.13), and subgroup analyses confirmed no '
'significant effect of different dosing strategies or baseline Vitamin D status on intubation '
'rates.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>Vitamin D '
'supplementation improves clinical outcomes in COVID-19 patients by reducing mortality and ICU '
'admission rates, particularly when administered continuously with a total dose of less than '
'100,000\u2009IU over 14\u2009days, and among those with baseline Vitamin D deficiency '
'(25OHD\u2009&lt;\u200930\u2009ng/mL). However, there were no significant effects on the '
'length of hospital stay or endotracheal intubation rates, regardless of the dosing regimen or '
'baseline Vitamin D levels. These findings emphasize the importance of considering both the '
'total dose over 14\u2009days and baseline Vitamin D status to optimize therapeutic '
'benefits.</jats:p></jats:sec>',
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