Prognostic and Therapeutic Role of Vitamin D in COVID-19: Systematic Review and Meta-analysis.

The Journal of clinical endocrinology and metabolism. 2022;107(5):1484-1502

Plain language summary

Vitamin D is implicated in optimum function of the immune system. Its deficiency has been linked to susceptibility to respiratory infections. It is postulated that vitamin D deficiency/insufficiency is also associated with COVID-19. The aim of this study was to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality and role of vitamin D in its treatment. This study is a systematic review and meta-analysis of seventy-six publications. Results show increased odds of developing COVID-19, progression to severe COVID-19 and death in people with vitamin D deficiency/insufficiency. In fact, people who developed COVID-19, severe COVID-19 and fatal disease had lower 25-hydroxy vitamin D concentration compared to people without COVID-19 or non-severe COVID-19 or non-fatal COVID-19 respectively. Authors conclude that Vitamin D deficiency/insufficiency may increase the risk of developing COVID-19 infection and susceptibility to more severe disease.

Abstract

PURPOSE Vitamin D deficiency/insufficiency may increase the susceptibility to coronavirus disease 2019 (COVID-19). We aimed to determine the association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, its severity, mortality, and role of vitamin D in its treatment. METHODS We searched CINAHL, Cochrane library, EMBASE, PubMED, Scopus, and Web of Science up to May 30, 2021, for observational studies on association between vitamin D deficiency/insufficiency and susceptibility to COVID-19, severe disease, and death among adults, and, randomized controlled trials (RCTs) comparing vitamin D treatment against standard care or placebo, in improving severity or mortality among adults with COVID-19. Risk of bias was assessed using Newcastle-Ottawa scale for observational studies and AUB-KQ1 Cochrane tool for RCTs. Study-level data were analyzed using RevMan 5.3 and R (v4.1.0). Heterogeneity was determined by I2 and sources were explored through prespecified sensitivity analyses, subgroup analyses, and meta-regressions. RESULTS Of 1877 search results, 76 studies satisfying eligibility criteria were included. Seventy-two observational studies were included in the meta-analysis (n = 1 976 099). Vitamin D deficiency/insufficiency increased the odds of developing COVID-19 (odds ratio [OR] 1.46; 95% CI, 1.28-1.65; P < 0.0001; I2 = 92%), severe disease (OR 1.90; 95% CI, 1.52-2.38; P < 0.0001; I2 = 81%), and death (OR 2.07; 95% CI, 1.28-3.35; P = 0.003; I2 = 73%). The 25-hydroxy vitamin D concentrations were lower in individuals with COVID-19 compared with controls (mean difference [MD] -3.85 ng/mL; 95% CI, -5.44 to -2.26; P ≤ 0.0001), in patients with severe COVID-19 compared with controls with nonsevere COVID-19 (MD -4.84 ng/mL; 95% CI, -7.32 to -2.35; P = 0.0001) and in nonsurvivors compared with survivors (MD -4.80 ng/mL; 95% CI, -7.89 to -1.71; P = 0.002). The association between vitamin D deficiency/insufficiency and death was insignificant when studies with high risk of bias or studies reporting unadjusted effect estimates were excluded. Risk of bias and heterogeneity were high across all analyses. Discrepancies in timing of vitamin D testing, definitions of severe COVID-19, and vitamin D deficiency/insufficiency partly explained the heterogeneity. Four RCTs were widely heterogeneous precluding meta-analysis. CONCLUSION Multiple observational studies involving nearly 2 million adults suggest vitamin D deficiency/insufficiency increases susceptibility to COVID-19 and severe COVID-19, although with a high risk of bias and heterogeneity. Association with mortality was less robust. Heterogeneity in RCTs precluded their meta-analysis.

Lifestyle medicine

Fundamental Clinical Imbalances : Immune and inflammation
Patient Centred Factors : Mediators/COVID-19
Environmental Inputs : Diet ; Nutrients
Personal Lifestyle Factors : Nutrition
Functional Laboratory Testing : Not applicable

Methodological quality

Jadad score : Not applicable
Allocation concealment : Not applicable

Metadata

Nutrition Evidence keywords : Vitamin D ; Deficiency