Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis.

This meta-analysis reported a positive association between vitamin D deficiency and the severity of the disease.

The aim of this study is to evaluate the association between vitamin D deficiency and COVID-19 severity, via an analysis of the prevalence of vitamin D deficiency and insufficiency in people with the disease.

Vitamin D deficiency was not associated with a higher chance of infection by COVID-19 (OR = 1.35; 95% CI = 0.80–1.88), however severe cases of COVID-19 present 64% (OR = 1.64; 95% CI = 1.30–2.09) more vitamin D deficiency compared with mild cases. A vitamin D concentration insufficiency increased hospitalization (OR = 1.81, 95% CI = 1.41–2.21) and mortality from COVID-19 (OR = 1.82, 95% CI = 1.06–2.58).

The meta-analysis included 8176 COVID-19 patients participating in 26 studies and the mean age was 58 years old (95% CI = 54–62).

• It is important to consider that the studies included are limited to the inclusion exclusion criteria of the study design and therefore may miss important studies with slightly different design but meaningful data.
• In addition, in order to conduct a meta-analysis the studies included must have similar endpoints to extract and in doing so researchers may group together studies that are not the same but will be analyzed as the same which can lead to skewed conclusions.
• A meta-analysis only includes studies that have been published and therefore information gathered may be subject to publication bias. This means that studies that show no effect or the opposite of the expected effect may not be published and therefore not included.
• The studies included showed various methodological divergences that prevent exploring the heterogeneity of the meta-analysis and conducting subgroup analyses due to confounding variables.
• Most of the studies chosen presented a high risk of bias because the studies were conducted using hospital-based samples using data taken from secondary recordings in patient records.
• Some studies did not clearly report the vitamin D dosage strategies or COVID-19 detection method.
• Confounding factors, such as age, sex, and the presence of comorbidities, were not used in most of the studies.

In conclusion, the results of the meta-analysis confirm the high prevalence of vitamin D deficiency in people with COVID-19, especially the elderly. We should add that vitamin D deficiency was not associated with COVID-19 infection. However, we observed a positive association between vitamin D deficiency and the severity of the disease. From this perspective, evaluating blood vitamin D levels could be considered in the clinical practice of health professionals. Moreover, vitamin D supplementation could be considered in patients with vitamin D deficiency and insufficiency, if they have COVID-19. However, there is no support for supplementation among groups with normal blood vitamin D values with the aim of prevention, prophylaxis or reducing the severity of the disease.

• This was a systematic review and meta-analysis which followed the established Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA)Guidelines.
• Before starting the literature review, search methods as well as criteria for which studies to include and exclude were established.
• A systematic review was carried out by 3 authors using PubMed, EMBASE, Web of Science, Science Direct and preprint Medrxiv and Scopus electronic databases published up to October 9 2020.
• The inclusion criteria were observational studies measuring serum vitamin D in adult and elderly subjects with COVID-19.
• The main outcome was vitamin D deficiency and COVID-19 severity.
• To assess bias of the included studies the Research Triangle Institute Item Bank (RTI–Item Bank) scale was used.

Pereira M, Dantas Damascena A, Galvão Azevedo LM, de Almeida Oliveira T, da Mota Santana J. Vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2020 Nov 4:1-9. doi: 10.1080/10408398.2020.1841090. Epub ahead of print. Update in: Crit Rev Food Sci Nutr. 2021 Aug 12;:1-6. PMID: 33146028.

Addendum: Damascena AD, Azevedo LMG, Oliveira TA, Santana JDM, Pereira M. Addendum to vitamin D deficiency aggravates COVID-19: systematic review and meta-analysis. Crit Rev Food Sci Nutr. 2021 Aug 12:1-6. doi: 10.1080/10408398.2021.1951652. Epub ahead of print. PMID: 34384300.