Calcifediol may prevent ICU admission, death in COVID-19

Treatment with calcifediol shortly after hospitalization with COVID-19 results in a significant reduction in intensive care unit (ICU) admission and death by more than 50 percent, reveals a study. In addition, baseline 25(OH)D levels are negatively associated with both ICU admission and mortality.

“These findings point to the relevance of attaining an adequate 25-hydroxyvitamin D (25[OH]D) status as soon as possible in the setting of SARS-CoV-2 infection,” the researchers said. “This is particularly attractive in the current epidemiologic situation as 25(OH)D deficiency is an easily modifiable factor.”

A team of researchers performed an observational cohort study from March to May 2020 among patients admitted to COVID-19 wards of Hospital del Mar in Barcelona, Spain. Of the 930 patients with COVID-19 enrolled, 92 were excluded due to previous calcifediol intake. Among those that remained in the analysis, 447 received calcifediol (532 μg on day 1 plus 266 μg on days 3, 7, 15, and 30), while 391 were not treated at the time of hospital admission (intention-to-treat).

In the intention-to-treat group, 53 patients received treatment later during ICU admission and were brought to the treated group for a second analysis. On a weight basis, calcifediol was about 3.2-fold more potent than cholecalciferol among healthy individuals.

More than one in 10 patients (12.2 percent) required ICU assistance: 20 (4.5 percent) out of 447 patients received calcifediol at admission whereas 82 (21 percent) out of 391 did not (p<0.001). [J Clin Endocrinol Metab 2021;106:e4017-e4027]

In logistic regression analysis of calcifediol treatment on ICU admission, adjusted by age, sex, linearized 25(OH)D levels at baseline, and comorbidities, patients with COVID-19 who received treatment had a lower chance of needing ICU assistance (odds ratio [OR], 0.13, 95 percent confidence interval [CI], 0.07–0.23).

Overall, the mortality rate stood at 10 percent. In the intention-to-treat analysis, 21 out of 447 patients (4.7 percent) who had received calcifediol at admission died, which were significantly fewer than those in the nontreated group with 62 out of 391 patients (15.9 percent) succumbing to COVID-19 (p=0.001). Adjusted results confirmed this lower mortality risk (OR, 0.21, 95 percent CI, 0.10–0.43), as did the second analysis (OR, 0.52, 95 percent CI, 0.27–0.99).

Studies with cholecalciferol had shown varied results, but one research reported that supplementation with vitamin D₃ in a bolus of 80,000 IU a month before or a week following diagnosis of COVID-19 resulted in less severe disease progression and better survival rate in frail, older patients. [J Steroid Biochem Mol Biol 2020;204:105771]

Additionally, regular vitamin D₃ supplementation in boluses administered during the year prior to diagnosis was found to reduce the risk of mortality and improve clinical outcomes in older patients with COVID-19. [Aging (Albany NY) 2020;12:24522-24534; Nutrients 2020;12:3799]

“Nonetheless, additional studies are necessary to fully elucidate the effects of circulating 25(OH)D levels and 25(OH)D treatment on COVID-19 disease severity in other populations with different baseline vitamin D status,” the researchers said.

“Calcifediol, a prehormone of the vitamin D endocrine system … was selected, rather than the more commonly used cholecalciferol or native vitamin D₃ threshold system nutrient, because of its excellent pharmacokinetic profile, including a high intestinal absorption, a time to a maximum of approximately 4 hours resulting in a rapid increase in serum 25(OH)D, and a half-life of 12 to 22 days,” they noted. [Osteoporos Int 2018;29:1697-1711]