Importance Patients with COVID-19 may exhibit 25-hydroxyvitamin D deficiency, but the beneficial effects of vitamin D3 supplementation in this disease remain to be proven by randomized controlled trials.
Objective To investigate the efficacy and safety of vitamin D3 supplementation in patients with severe COVID-19.
Design, Setting, and Participants This is a multicenter, double-blind, randomized, placebo-controlled trial conducted in two centers (a quaternary hospital and a field hospital) in Sao Paulo, Brazil. The trial included 240 hospitalized patients with severe COVID-19. The study was conducted from June 2, 2020 to October 7, 2020.
Interventions Patients were randomly allocated (1:1 ratio) to receive either a single oral dose of 200,000 IU of vitamin D3 or placebo.
Main Outcomes and Measures The primary outcome was hospital length of stay, defined as hospital discharge from the date of randomization or death. Secondary outcomes were mortality, admission to ICU, mechanical ventilation requirement, and serum levels of 25-hydroxyvitamin D, creatinine, calcium, C-reactive protein, and D-dimer.
Results Of 240 randomized patients (mean age, 56 years; 56% men), 232 (96.7%) were included in the primary analysis. Log-rank test showed that hospital length of stay was comparable between the vitamin D3 supplementation and placebo groups (7.0 days [95% CI, 6.1 to 7.9] and 7.0 days [95% CI, 6.2 to 7.8 days]; hazard ratio, 1.12 [95% CI, 0.9 to 1.5]; P = .379; respectively). The rate of mortality (7.0% vs 5.1%; P = .590), admission to ICU (15.8% vs 21.2%; P = .314), and mechanical ventilation requirement (7.0% vs 14.4%; P = .090) did not significantly differ between groups. Vitamin D3 supplementation significantly increased serum 25-hydroxyvitamin D levels compared to placebo (difference, 24.0 ng/mL [95% CI, 21.0% to 26.9%]; P = .001). No adverse events were observed.
Conclusions and Relevance Among hospitalized patients with severe COVID-19, vitamin D3 supplementation was safe and increased 25-hydroxyvitamin D levels, but did not reduce hospital length of stay or any other relevant outcomes vs placebo. This trial does not support the use of vitamin D3 supplementation as an adjuvant treatment of patients with COVID-19.