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Meta-Analysis
. 2022 Jul 6;17(7):e0268396.
doi: 10.1371/journal.pone.0268396. eCollection 2022.

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

Oriana D'Ecclesiis  1 , Costanza Gavioli  2 , Chiara Martinoli  1 , Sara Raimondi  1 , Susanna Chiocca  1 , Claudia Miccolo  1 , Paolo Bossi  3 , Diego Cortinovis  4 , Ferdinando Chiaradonna  5 , Roberta Palorini  5 , Federica Faciotti  1 , Federica Bellerba  1 , Stefania Canova  4 , Costantino Jemos  6 , Emanuela Omodeo Salé  6 , Aurora Gaeta  1 , Barbara Zerbato  5 , Patrizia Gnagnarella  2 , Sara Gandini  1
Affiliations
Meta-Analysis

Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis

Oriana D'Ecclesiis et al. PLoS One. .

Abstract

To assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D, we conducted a systematic review up to April 2021. We summarised data from 38 eligible studies, which presented risk estimates for at least one endpoint, including two RCT and 27 cohort-studies: 205565 patients with information on 25OHD status and 2022 taking vitamin D supplementation with a total of 1197 admitted to the ICU or who needed invasive mechanical ventilation or intubation and hospital stay, and more than 910 Covid-19 deaths. Primary outcomes were severity and mortality and the main aim was to evaluate the association with vitamin D supplementation. Random effects models showed that supplementation was associated with a significant lower risk of both Covid-19 severe disease (SRR 0.38, 95% CI 0.20-0.72, 6 studies) and mortality (SRR 0.35, 95% CI 0.17-0.70, 8 studies). There were no statistically significant dose differences between studies: summary estimates with regular doses remain statistically significant, suggesting that higher doses are not necessary. For patients on vitamin D supplementation, a greater reduction in mortality risk emerged in older individuals and at higher latitudes. Regarding the quality of studies, assessed using the New Castle-Ottawa quality scale, the analysis revealed in most cases no statistically significant differences between low, medium or high quality studies. We found significant associations of vitamin D supplementation with Covid-19, encompassing risks of disease worsening and mortality, especially in seasons characterized by 25OHD deficiency and with not severe patients. Dedicated randomized clinical studies are encouraged to confirm these results.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Flow chart.
Study flow-chart for the process of selecting the enrolled studies.
Fig 2
Fig 2. Forest plot of risk estimates of infection for low vs high vitamin D levels.
Forest plot: Ticks represent effect estimates of individual studies with their 95% confidence intervals. Raindrops and shading represent the probability density for a probability of 0.95 with height of raindrop and color saturation proportional to the weight assigned to the study in the meta-analysis. The diamond represents the overall result and 95% confidence interval of the fixed-effect meta-analysis.
Fig 3
Fig 3. Forest plot of risk estimates of severity for low vs high vitamin D levels.
Fig 4
Fig 4. Forest plot of risk estimates of severity for vitamin D supplementation vs not supplementation.
Fig 5
Fig 5. Forest plot of risk estimates of mortality for low vs high vitamin D levels.
Fig 6
Fig 6. Forest plot of risk estimates of mortality for vitamin D supplementation vs not supplementation.
See this image and copyright information in PMC

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