Vitamin D supplementation for the treatment of COVID-19: a living systematic review.

Living systematic review of randomized trials in adults with confirmed COVID-19 comparing vitamin D supplementation with placebo or standard care. The included active intervention arms came from 4 studies and 305 participants overall, spanning hospitalized patients with moderate to severe disease and outpatients with mild or asymptomatic disease.

Vitamin D supplementation was tested in several oral regimens, including calcifediol (25(OH) vitamin D3) 0.532 mg on day 1, then 0.266 mg on days 3 and 7 and weekly thereafter until discharge or ICU admission; cholecalciferol (vitamin D3) 200,000 IU as a single oral dose; and cholecalciferol 60,000 IU/day for 7 days with continued dosing if 25(OH)D remained low. Comparators were placebo or standard care.

Overall, there is insufficient evidence to determine whether vitamin D helps or harms adults treated for COVID-19. One small trial in hospitalized patients reported fewer ICU admissions with calcifediol, 1/50 versus 13/26, RR 0.04, 95% CI 0.01 to 0.29, but mortality was not clearly improved, 0/50 versus 2/26, RR 0.11, 95% CI 0.01 to 2.13. A larger Brazilian trial found no clear benefit for mortality, 9/119 versus 6/118, RR 1.49, 95% CI 0.55 to 4.04, mechanical ventilation, 9/119 versus 17/118, RR 0.52, 95% CI 0.24 to 1.13, or ICU admission, 19/119 versus 25/118, RR 0.75, 95% CI 0.44 to 1.29. Safety data were limited; one vomiting event was reported and no hypercalcemia was observed in the outpatient trial.

The evidence base is small and very uncertain, with only 4 trials and substantial heterogeneity in vitamin D form, dose, timing, baseline vitamin D status, and outcome reporting. Safety information was sparse, several prespecified outcomes were not reported across studies, and generalizability is limited by mixed settings and disease severities. Risk of bias concerns and inconsistent study quality further weaken confidence in the findings.