Effect of a Single High Dose of Vitamin D₃ on Hospital Length of Stay in Patients With Moderate to Severe COVID-19

Abstract

IMPORTANCEThe efficacy of vitamin D 3 supplementation in coronavirus disease 2019 remains unclear.OBJECTIVE To investigate the effect of a single high dose of vitamin D 3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTSThis was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020.INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D 3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURESThe primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTSOf 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D 3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D 3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D 3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention.CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D 3 , compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D 3 for treatment of moderate to severe COVID-19.

Vitamin D and COVID-19 susceptibility and severity in the COVID-19 Host Genetics Initiative: A Mendelian randomization study

“…However, the follow-up time for mortality varied, and the open-label design put it at high risk of bias. The second [16] was a larger study (n=240) using a double-blind design, and showed no effect on mortality, risk of mechanical ventilation, and length of stay. Nevertheless, questions remain on the use of pre-illness vitamin D supplementation and its effect on disease susceptibility.…”

Common drugs, vitamins, nutritional supplements and COVID‑19 mortality

“…A vitamin D/magnesium/vitamin B12 combination in older-aged COVID-19 patients was associated with a significant reduction in the proportion of patients with clinical deterioration requiring oxygen support, intensive care support, or both (15). Vitamin D may be a critical host factor to prevent COVID-19 (17), although this hypothesis remains controversial (18,19). To prevent the cytokine storm, the use of N-acetylcysteine in both the prevention and adjuvant therapy of COVID-19 has been suggested; however, the UKB did not have information on this substance (20).…”

Association of Calcitriol Supplementation with Reduced COVID-19 Mortality in Patients with Chronic Kidney Disease: A Population-based Study

“…Two small-sized observational studies have shown divergent results, either with a trend to an increased mortality in patients supplemented with calcifediol [25], or a better survival in geriatric patients under cholecalciferol supplementation [26]. In addition, three low-powered clinical trials using cholecalciferol or calcifediol supplementation in hospitalized patients with COVID-19 have not observed any significant reduction in mortality [27][28][29].…”