Effect of Single High Dose Vitamin D Substitution in Hospitalized COVID-19 Patients with Vitamin D Deficiency on Length of Hospital Stay

Abstract

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.

Effect of Vitamin D3 Supplementation on Severe COVID-19: A Meta-Analysis of Randomized Clinical Trials

“…All included studies are randomized controlled trials with a control group containing vitamin D3 supplementation. Among these studies, five studies had a placebo in the control group [20][21][22][23][24], four studies had no supplementation in the control group [25][26][27][28] and four studies had a standard dose of vitamin D3 [29][30][31][32]. Two studies included patients admitted to the intensive care unit [21,32].…”

“…One study included pediatric patients [31] and one study enrolled older adults [26]. The studies were carried out in different countries, including Spain [28,29], Brazil [20], Russia [21,30], Switzerland [27], Mexico [31], Egypt [25], France [26], Argentina [22], Belgium [23], Iran [24] and Croatia [32]. Table 1 shows the characteristics of the included studies.…”

“…(B) Mean difference in duration of any supplemental oxygenation. OToxygen therapies; MV-mechanical ventilation; NIMV or NIV-non-invasive mechanical ventilation or non-invasive ventilation; IMV-invasive mechanical ventilation; OD-oxygen devices; SO-supplemental oxygenation; SV-progression to a superior ventilation modality; SCO-supplemental conventional oxygen[20][21][22][23][24][25]27,28,[30][31][32].…”

Pharmacological evaluation of vitamin D in COVID-19 and long COVID-19: recent studies confirm clinical validation and highlight metformin to improve VDR sensitivity and efficacy

“…All randomized controlled trials confirm the clinical safety of high doses of vitamin D supplements, however, benefit has not been observed in any of the COVID-19 outcomes including length of hospital stay, disease incidence, number of days on respiratory support, mortality, admission to Intensive care unit, and prognosis. Four randomized controlled trials(44% of studies) evaluated the effect of a single oral bolus dose of cholecalciferol (100,000–500,000 IU) on length of hospital stay and respiratory deterioration, and found no effect in 649 patients with insufficient vitamin D level (Cannata-Andía et al 2022 ; Mariani et al 2022 ; Jaun et al 2023 ; Abroug et al 2023 ). Eight cohort studies and eight randomized controlled studies involving 3359 patients with COVID-19 were included in the only meta- analysis study (Zhang et al 2023 ).…”