Mathematical analysis of Cordoba calcifediol trial suggests strong role for Vitamin D in reducing ICU admissions of hospitalized COVID-19 patients

Jungreis, I.; Kellis, M.

A randomized controlled trial of calcifediol (25-hydroxyvitamin D3) as a treatment for hospitalized COVID-19 patients in Cordoba, Spain, found that the treatment was associated with reduced ICU admissions with very large effect size and high statistical significance, but the study has had limited impact because it had only 76 patients and imperfect blinding, and did not measure vitamin D levels pre- and post-treatment or adjust for several comorbidities. Here we reanalyze the results of the study using rigorous and well established statistical techniques, and find that the randomization, large effect size, and high statistical significance address many of these concerns. In particular, we show that decreased ICU admissions were not due to uneven distribution of comorbidities or other prognostic indicators, to imperfect blinding, or to chance, but were instead associated with the calcifediol intervention. We conclude that the Cordoba study provides sufficient evidence to warrant immediate, well-designed pivotal clinical trials of calcifediol in a broader cohort of inpatients and outpatients with COVID-19, and to consider broad adoption of calcifediol treatment for vitamin-D-deficient hospitalized COVID-19 patients.