Vitamin D and SARS-CoV2 Infection, Severity and Mortality: A Systematic Review and Meta-analysis

Vitamin D supplementation was associated with a significantly lower risk of both Covid-19 severe disease and mortality in this systematic review.

• Supplementation was associated with a significantly lower risk of both Covid-19 severe disease) and mortality.  
• 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. 

27 cohort-studies including 205,565 patients.

There were many differences in study designs including dosing and when serum levels were measured. 

In conclusion, our meta-analysis of both observational and interventional studies suggests that people with COVID-19 taking VD supplementation, may have a reduced risk of both severity and mortality compared to subjects who do not take VD supplementation, although further RCT are necessary to draw a definitive conclusion on the causal link. Our meta-analysis takes into account the most recent studies and, thanks to the numerous analyses and investigations carried out, could encourage the development of hypotheses that will necessarily have to be tested in randomized controlled experiments to better assess and clarify the role of VD with COVID-19.

• A review was done to assess the evidence on SARS-CoV2 infection and Covid-19 in relation to deficiency and supplementation of vitamin D.
• PUBMED, Ovid Medline, EMBASE, and ISI Web of Science up to April 2021 were searched.
• The publications were retrieved using search terms and text words: “Vitamin D” or “25-OH-D” or “25-hydroxycholecalciferol” or “25-hydroxyvitamin D” or “25-hydroxyvitamin D3” or “cholecalciferol” or “calcitriol” or “hydroxycholecalciferols” in combination with “Covid” or “SARS-CoV2” or “Covid-19” or “Covid-19 mortality” or “Covid-19 death” or “Covid-19 severity” or “SARS-CoV2 infection” without any restriction. The database search was supplemented by consulting the bibliography of the articles, reviews and published meta-analysis. 
• Inclusion criteria 1) Research involved individuals tested for SARS-CoV2, or Covid-19 positive; 2) Serum VD levels were available and tested at baseline or within one year from study start, or information was available on baseline VDD, or VD regular use or supplementation for interventional studies; 3) Sufficient information was available to estimate the risk estimate and 95% confidence intervals (CIs) of SARS-CoV2 infection or Covid-19 progression; 4) Studies had to be independent and not duplicate results published in other articles.

D’Ecclesiis O, Gavioli C, Martinoli C, Raimondi S, Chiocca S, Miccolo C, Bossi P, Cortinovis D, Chiaradonna F, Palorini R, Faciotti F, Bellerba F, Canova S, Jemos C, Salé EO, Gaeta A, Zerbato B, Gnagnarella P, Gandini S. Vitamin D and SARS-CoV2 infection, severity and mortality: A systematic review and meta-analysis. PLoS One. 2022 Jul 6;17(7):e0268396. doi: 10.1371/journal.pone.0268396. PMID: 35793346; PMCID: PMC9258852.