High-dose vitamin D substitution in patients with COVID-19: study protocol for a randomized, double-blind, placebo-controlled, multi-center study-VitCov Trial

Trials. 2022 Feb 4;23(1):114. doi: 10.1186/s13063-022-06016-2.


Background: The coronavirus disease 19 (COVID-19) pandemic has caused millions of deaths, and new treatments are urgently needed. Factors associated with a worse COVID-19 prognosis include old age (> 65 years), ethnicity, male sex, obesity, and people with comorbidities. Furthermore, vitamin D deficiency was reported as a predictor of poor prognosis in patients with acute respiratory failure due to COVID-19. According to a recent clinical case series, vitamin D deficiency is a modifiable risk factor, which has the prospect of reducing hospital stay, intensive care, and fatal outcomes. Vitamin D has potent immunomodulatory properties, and its supplementation might improve important outcomes in critically ill and vitamin D-deficient COVID-19 patients. Despite the evidence that supports an association between vitamin D deficiency and COVID-19 severity, there is uncertainty about the direct link. Therefore, the aim of the trial is to assess if high-dose vitamin D supplementation has a therapeutic effect in vitamin D-deficient patients with COVID-19.

Methods: As the trial design, a randomized, placebo-controlled, double-blind, multi-center approach was chosen to compare a high single dose of vitamin D (140,000 IU) followed by treatment as usual (TAU) (VitD + TAU) with treatment as usual only (placebo + TAU) in patients with COVID-19 and vitamin D deficiency.

Discussion: Vitamin D substitution in patients with COVID-19 and vitamin D deficiency should be investigated for efficacy and safety. The study aim is to test the hypothesis that patients with vitamin D deficiency suffering from COVID-19 treated under standardized conditions in hospital will recover faster when additionally treated with high-dose vitamin D supplementation. Latest studies suggest that vitamin D supplementation in patients with COVID-19 is highly recommended to positively influence the course of the disease. With this randomized controlled trial, a contribution to new treatment guidelines shall be made.

Trial registration: ClinicalTrials.gov NCT04525820 and SNCTP 2020-01401.

Keywords: COVID-19; Coronavirus; SARS-CoV-2; Vitamin D; Vitamin D deficiency.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Aged
  • COVID-19*
  • Double-Blind Method
  • Humans
  • Male
  • Multicenter Studies as Topic
  • Pandemics
  • Randomized Controlled Trials as Topic
  • SARS-CoV-2
  • Treatment Outcome
  • Vitamin D / adverse effects
  • Vitamin D Deficiency* / diagnosis
  • Vitamin D Deficiency* / drug therapy
  • Vitamins / adverse effects


  • Vitamins
  • Vitamin D

Associated data

  • ClinicalTrials.gov/NCT04525820