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Active vitamin D [1,25(OH)2D3—calcitriol] is a secosteroid hormone whose receptor is expressed on all cells of the immune system. Vitamin D has a global anti-inflammatory effect and its role in the management of a SARS-CoV-2 infection has been investigated since the beginning of the COVID-19 pandemic.
Trials | Study Population | Patients’ Cohorts’ Characteristics | Recruitment Period | Time of Follow-Up | Supplementation Regimen | Effects of Vitamin D Supplementation |
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Treatment with 25-hydroxyvitamin D3 (calcifediol) is associated with a reduction in the blood neutrophil-to-lymphocyte ratio marker of disease severity in hospitalized patients with COVID-19: a pilot multicenter, randomized, placebo-controlled, double-blinded clinical trial (Maghbooli Z et al., 2021, Ref. [36]) | 106 COVID-19 adult hospitalized patients with 25(OH)D3 serum concentrations < 30 ng/mL | 53 patients on vitamin D3 group 53 patients on placebo group |
May 2020–October 2020 | 2 months | 25 mcg of 25(OH)D3 daily (equivalent to 3000–6000 IU of cholecalciferol) in addition to standard care |
Increase in neutrophils to lymphocytes ratio |
Short term, high-dose vitamin D supplementation for COVID-19 disease: a randomized, placebo-controlled, study (SHADE study) (Rastogi A et al. 2022, Ref. [37]) | 40 COVID-19 hospitalized patients with mild symptoms or asymptomatic | 16 patients with 25(OH)D serum concentrations < 20 ng/mL received vitamin D3 treatment 24 patients received placebo |
2020 | 21 days | 60,000 IU daily of cholecalciferol (oral nano-liquid droplets) for a week in addition to standard care. If 25(OH)D serum concentrations were < 50 ng/mL in the treatment group, supplementation was continued for another week | Faster healing Decrease in serum fibrinogen |
Positive effects of vitamin D supplementation in patients hospitalized for COVID-19: a randomized, double-blind, placebo-controlled trial (De Niet S et al., 2022, Ref. [38]) | 50 COVID-19 hospitalized patients with 25(OH)D3 serum concentrations < 20 ng/mL | 26 patients received vitamin D3 supplementation 24 patients received placebo |
August 2020–August 2021 | 9 weeks | 25,000 IU daily of cholecalciferol over four consecutive days followed by 25,000 IU weekly of cholecalciferol in addition to best available treatment | Decrease in length of hospital stay Decrease in duration of supplemental oxygen request Improve of clinical recovery, assessed by WHO scale |
Efficacy and safety of vitamin D supplementation to prevent COVID-19 in frontline healthcare workers. A randomized clinical trial. (Villasis-Keever. et al., 2022, Ref. [39]) | 321 SARS-CoV-2 free healthcare workers not receiving vitamin D supplementation | 160 healthcare workers received vitamin D supplementation 161 healthcare workers received placebo |
15 July 2020–30 December 2020 | 30 days | 4000 IU daily of cholecalciferol capsules | Lower infection rate without serious adverse events |
Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: a randomized clinical trial (Murai IH et al., 2021, Ref. [40]) | 240 COVID-19 adult hospitalized patients | 120 patients received vitamin D supplementation 120 patients received placebo |
2 June 2020–7 October 2020 | Hospitalization period | 200,000 IU of cholecalciferol in a single oral dose | No effects on in-hospital mortality, admission to intensive care unit or need for mechanical ventilation |
High-dose vitamin D versus placebo to prevent complications in COVID-19 patients; multicentre randomized controlled clinical trial (Mariani J et al. 2022, Ref. [41]) | 218 COVID-19 adult hospitalized patients | 115 patients received vitamin D3 supplementation 103 patients received placebo |
14 August 2020–22 June 2021 | Hospitalization period | 500,000 IU of oral cholecalciferol (5 capsules of 100,000 IU) in a single oral dose | No change in the respiratory Sepsis related Organ Failure Assessment (SOFA) score between baseline and the highest value recorded up to day 7 No difference for length of hospital stays, intensive care unit admissions and in-hospital mortality |
Prevention of COVID-19 and other acute respiratory infections with cod liver oil supplementation, a low dose vitamin D supplement: quadruple blinded, randomised placebo controlled trial (Brunvoll SH et al., 2017, Ref. [42]) | 34,601 adults not receiving vitamin D supplementation | 17,278 adults received cod liver oil 17,323 adults received placebo |
10 November 2020–2 June 2021 | 6 months | 400 IU daily of cholecalciferol | No decrease in the incidence of SARS-CoV-2 infection and serious COVID-19 (self-reported dyspnoea, admission to hospital, death) |