Low Serum 25-hydroxyvitamin D (Vitamin D) Level Is Associated With Susceptibility to COVID-19, Severity, and Mortality: A Systematic Review and Meta-Analysis
Mohammad Rizki Akbar, Arief Wibowo, Raymond Pranata, Budi Setiabudiawan
Frontiers in Nutrition, doi:10.3389/fnut.2021.660420
Background: This systematic review and meta-analysis aimed to assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility to COVID-19, severity, and mortality related to COVID-19. Methods: Systematic literature searches of PubMed, Scopus, and Embase database up until 9 December 2020. We include published observational prospective and retrospective studies with information on 25-OHD that reported main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary outcome was susceptibility and severe COVID-19. Results: There were 14 studies comprising of 999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection compared to the control group (OR = 2.71 [1.72, 4.29], p < 0.001; I 2 : 92.6%). Higher rate of severe COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], p = 0.003; I 2 : 55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7 .00], p = 0.011; I 2 : 80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. Meta-regression analysis showed that the association between low serum 25-OHD and mortality was affected by male gender (OR = 1.22 [1.08, 1.39], p = 0.002), diabetes (OR = 0.88 [0.79, 0.98], p = 0.019).
Conclusion: Low serum 25-OHD level was associated with COVID-19 infection, severe presentation, and mortality.
AUTHOR CONTRIBUTIONS MA: conceptualization, investigation, writing -original draft, writing -review and editing, and supervision. AW: data curation, investigation, and writing -original draft. RP: conceptualization, methodology, software, data curation, formal analysis, statistical analysis, investigation, validation, and writing -original draft. BS: investigation, and writing -review and editing. All authors contributed to the article and approved the submitted version.
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. Copyright © 2021 Akbar, Wibowo, Pranata and Setiabudiawan. This is an openaccess article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
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'abstract': '<jats:p><jats:bold>Background:</jats:bold> This systematic review and meta-analysis aimed to '
'assess whether low serum 25-hydroxyvitamin D (25-OHD) level is associated with susceptibility '
'to COVID-19, severity, and mortality related to '
'COVID-19.</jats:p><jats:p><jats:bold>Methods:</jats:bold> Systematic literature searches of '
'PubMed, Scopus, and Embase database up until 9 December 2020. We include published '
'observational prospective and retrospective studies with information on 25-OHD that reported '
'main/secondary outcome. Low serum 25-OHD refers to participants with serum 25-OHD level below '
'a cut-off point ranging from 20 to 30 ng/mL. Other cut-off values were excluded to reduce '
'heterogeneity. The main outcome was mortality defined as non-survivor/death. The secondary '
'outcome was susceptibility and severe '
'COVID-19.</jats:p><jats:p><jats:bold>Results:</jats:bold> There were 14 studies comprising of '
'999,179 participants. Low serum 25-OHD was associated with higher rate of COVID-19 infection '
'compared to the control group (OR = 2.71 [1.72, 4.29], <jats:italic>p</jats:italic> &lt; '
'0.001; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: 92.6%). Higher rate of severe '
'COVID-19 was observed in patients with low serum 25-OHD (OR = 1.90 [1.24, 2.93], '
'<jats:italic>p</jats:italic> = 0.003; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: '
'55.3%), with a sensitivity of 83%, specificity of 39%, PLR of 1.4, NLR of 0.43, and DOR of 3. '
'Low serum 25-OHD was associated with higher mortality (OR = 3.08 [1.35, 7.00], '
'<jats:italic>p</jats:italic> = 0.011; <jats:italic>I</jats:italic><jats:sup>2</jats:sup>: '
'80.3%), with a sensitivity of 85%, specificity of 35%, PLR of 1.3, NLR of 0.44, and DOR of 3. '
'Meta-regression analysis showed that the association between low serum 25-OHD and mortality '
'was affected by male gender (OR = 1.22 [1.08, 1.39], <jats:italic>p</jats:italic> = 0.002), '
'diabetes (OR = 0.88 [0.79, 0.98], <jats:italic>p</jats:italic> = '
'0.019).</jats:p><jats:p><jats:bold>Conclusion:</jats:bold> Low serum 25-OHD level was '
'associated with COVID-19 infection, severe presentation, and mortality.</jats:p>',
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