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. eCollection 2022.


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.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • COVID-19*
  • Dietary Supplements
  • Humans
  • RNA, Viral
  • SARS-CoV-2
  • Vitamin D* / therapeutic use
  • Vitamins / therapeutic use


  • RNA, Viral
  • Vitamins
  • Vitamin D

Grants and funding

Grant Regione Lombardia. (DECRETO N. 7082 Del 17/06/2020. Identificativo Atto n. 366: COVitaminD Trial: prevenzione di complicanze da COVID-19 in pazienti oncologici). The European Institute of Oncology, Milan, Italy is partially supported by the Italian Ministry of Health with Ricerca Corrente and 5×1,000 funds.Federica Bellerba is a Ph.D. student within the European School of Molecular Medicine (SEMM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.