Vitamin D and its role in the coronavirus-19 disease (COVID-19) pandemic has been controversially discussed, with inconclusive evidence about vitamin D3 (cholecalciferol) supplementation in COVID-19 patients. Vitamin D metabolites play an important role in the initiation of the immune response and can be an easily modifiable risk factor in 25-hydroxyvitamin D₃ (25(OH)D₃)-deficient patients. This is a multicenter, randomized, placebo-controlled double-blind trial to compare the effect of a single high dose of vitamin D₃ followed by treatment as usual (TAU) of daily vitamin D₃ daily until discharge versus placebo plus TAU in hospitalized patients with COVID-19 and 25(OH)D₃-deficiency on length hospital stay. We included 40 patients per group and did not observe a significant difference in the median length of hospital stay (6 days in both groups, p = 0.920). We adjusted the length of stay for COVID-19 risk factors (β = 0.44; 95% CI: -2.17-2.22), and center (β = 0.74; 95% CI: -1.25-2.73). The subgroup analysis in patients with severe 25(OH)D₃-deficiency (<25 nmol/L) showed a non-significant reduction in the median length of hospital stay in the intervention group (5.5 vs. 9 days, p = 0.299). The competing risk model with death did not reveal significant differences between the group in the length of stay (HR = 0.96, 95% CI 0.62-1.48, p = 0.850). Serum 25(OH)D₃ level increased significantly in the intervention group (mean change in nmol/L; intervention: +26.35 vs. control: -2.73, p < 0.001). The intervention with 140,000 IU vitamin D₃ + TAU did not significantly shorten the length of hospital stay but was effective and safe for the elevation of serum 25(OH)D₃ levels.

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