The relationship between the severity and mortality of SARS-CoV-2 infection and 25-hydroxyvitamin D concentration - a metaanalysis

Adv Respir Med. 2021;89(2):145-157. doi: 10.5603/ARM.a2021.0037.


Introduction: There is increasing scientific interest in the possible association between hypovitaminosis D and the risk of SARS-CoV-2 infection severity and/or mortality.

Objective: To conduct a metanalysis of the association between 25-hydroxyvitamin D (25(OH)D) concentration and SARS-CoV-2 infection severity or mortality.

Material and methods: We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for studies published between December 2019 and December 2020. Effect statistics were pooled using random effects models. The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Targeted outcomes: mortality and severity proportions in COVID-19 patients with 25(OH)D deficiency, defined as serum 25(OH)D < 50 nmol/L.

Results: In the 23 studies included (n = 2692), the mean age was 60.8 (SD ± 15.9) years and 53.8% were men. Results suggested that vitamin 25(OH)D deficiency was associated with increased risk of severe SARS-CoV-2 disease (RR 2.00; 95% CI 1.47-2.71, 17 studies) and mortality (RR 2.45; 95% CI 1.24-4.84, 13 studies). Only 7/23 studies reported C-reactive protein values, all of which were > 10 mg/L. Conclusions 25(OH)D deficiency seems associated with increased SARS-CoV-2 infection severity and mortality. However, findings do not imply causality, and randomized controlled trials are required, and new studies should be designed to determine if decreased 25(OH)D is an epiphenomenon or consequence of the inflammatory process associated with severe forms of SARS-CoV-2. Meanwhile, the concentration of 25(OH)D could be considered as a negative acute phase reactant and a poor prognosis in COVID-19 infection.

Keywords: 25-hydroxyvitamin D; COVID-19; SARS-CoV-2; metanalysis; mortality; severity; vitamin D.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Age Factors
  • COVID-19 / blood
  • COVID-19 / mortality*
  • Female
  • Humans
  • Male
  • Severity of Illness Index*
  • Vitamin D / analogs & derivatives*
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / epidemiology*


  • Vitamin D
  • 25-hydroxyvitamin D