Calcifediol Treatment and COVID-19-Related Outcomes

J Clin Endocrinol Metab. 2021 Sep 27;106(10):e4017-e4027. doi: 10.1210/clinem/dgab405.


Context: COVID-19 is a major health problem because of saturation of intensive care units (ICU) and mortality. Vitamin D has emerged as a potential treatment able to reduce the disease severity.

Objective: This work aims to elucidate the effect of 25(OH)D3 (calcifediol) treatment on COVID-19-related outcomes.

Methods: This observational cohort study was conducted from March to May 2020, among patients admitted to COVID-19 wards of Hospital del Mar, Barcelona, Spain. A total of 930 patients with COVID-19 were included; 92 were excluded because of previous calcifediol intake. Of the remaining 838, a total of 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), whereas 391 were not treated at the time of hospital admission (intention-to-treat). Of the latter, 53 patients were treated later during ICU admission and were allocated in the treated group in a second analysis. In healthy individuals, calcifediol is about 3.2-fold more potent on a weight basis than cholecalciferol. Main outcome measures were ICU admission and mortality.

Results: ICU assistance was required by 102 (12.2%) participants. Out of 447 patients treated with calcifediol at admission, 20 (4.5%) required the ICU, compared to 82 (21%) out of 391 nontreated (P < .001). Logistic regression of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25-hydroxyvitamin D levels at baseline, and comorbidities showed that treated patients had a reduced risk of requiring the ICU (odds ratio [OR] 0.13; 95% CI 0.07-0.23). Overall mortality was 10%. In the intention-to-treat analysis, 21 (4.7%) out of 447 patients treated with calcifediol at admission died compared to 62 patients (15.9%) out of 391 nontreated (P = .001). Adjusted results showed a reduced mortality risk with an OR of 0.21 (95% CI, 0.10-0.43). In the second analysis, the obtained OR was 0.52 (95% CI, 0.27-0.99).

Conclusion: In patients hospitalized with COVID-19, calcifediol treatment significantly reduced ICU admission and mortality.

Keywords: COVID-19; ICU admission; calcifediol; mortality; vitamin D.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • COVID-19 / blood
  • COVID-19 / epidemiology
  • COVID-19 Drug Treatment*
  • Calcifediol / administration & dosage*
  • Cholecalciferol / administration & dosage
  • Cohort Studies
  • Comorbidity
  • Female
  • Hospital Mortality
  • Hospitalization
  • Humans
  • Intensive Care Units
  • Male
  • Middle Aged
  • SARS-CoV-2*
  • Spain
  • Treatment Outcome
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood
  • Vitamin D Deficiency / blood
  • Vitamin D Deficiency / complications
  • Vitamin D Deficiency / epidemiology


  • Vitamin D
  • Cholecalciferol
  • 25-hydroxyvitamin D
  • Calcifediol