Single, High Dose Vitamin D Supplementation in Vitamin D Deficient Severe COVID-19: Randomized, Double-Blind, Placebocontrol Study (Shade-S)

ABSTRACT

Aim and background: Efficacy of therapeutic vitamin D3 supplementation for ICU outcomes in severe COVID-19 is sparingly studied. Objective: Effect of single high-dose vitamin D3 supplementation on sequential organ failure assessment (SOFA) score in patients with moderate to severe COVID-19 disease. Materials and methods: A single centre, randomized, doubleblind, placebo-controlled study was carried out among 90 patients with moderate to severe COVID-19 ARDS defined by PaO2/FiO2 <200. Participants received 0.6 million IU vitamin D3 (oral nanoformulation) (intervention) or placebo (equal volume, oral). SOFA score on day-3, -7, -10, and -14 was measured. The primary outcome was a change in day-7 SOFA score from admission. Pre-specified secondary outcomes were day 10 and day-14 SOFA score, change in PaO2/FiO2 ratio, in-hospital all-cause mortality, and inflammatory cytokine levels. Results: A total of 358 patients were screened and 90 patients (45 in each group) were included. 25(OH)D3 levels were 12.0 (10.0-16.0) and 12.7 (12-18) ng/mL (p = 0.059) at study entry;60 (54.40 to 65.59) ng/mL and 3.8 [1.05 to 6.55] at day-3 in the intervention and placebo group, respectively. The SOFA score on day-7 was better in the treatment group [intergroup difference was -2 (95% CI, -3.99 to -0.01, p = 0.009) with effect-size of r = 0.35 (95% CI, 0.09-0.55). The all-cause mortality with intervention was 24.4% compared to 44.4% (p = 0.046) in the control group. A significant improvement in the day-7 PaO2/FiO2 ratio [200.50 (101.01-291.30) and 110.70 (66.20-166.50), p = 0.003;intergroup difference -98.6 (40.70 to 156.49)], a decrease in CRP [-48.63 (-80.78 to -16.48) and 5.4 (-17.62 to 28.42), p = 0.042)], ferritin [-412.3 (-736.29 to -88.31) and 41.5 (-293.68 to 376.68), p = 0.018] was observed in the intervention and placebo groups, respectively. Conclusion: Single high-dose oral cholecalciferol supplementation to increase vitamin D3 >50 ng/mL improves the SOFA score and reduces in-hospital mortality in vitamin-D deficient patients with severe COVID-19.