“Effect of calcifediol treatment and best available therapy versus best available therapy on intensive care unit admission and mortality among patients hospitalized for COVID-19: A pilot randomized clinical study”

Under a Creative Commons license
open access

Highlights

?

The vitamin D endocrine system have a variety of actions on cells and tissues involved in COVID-19 progression.

?

Early calcifediol (25-hydroxyvitamin D) treatment to hospitalized COVID-19 patients significantly reduced intensive care unit admissions-Calcifediol seems to be able to reduce severity of the COVID-19.

?

Calcifediol seems to be able to reduce severity of the disease.

Abstract

Objective

The vitamin D endocrine system may have a variety of actions on cells and tissues involved in COVID-19 progression especially by decreasing the Acute Respiratory Distress Syndrome. Calcifediol can rapidly increase serum 25OHD concentration. We therefore evaluated the effect of calcifediol treatment, on Intensive Care Unit Admission and Mortality rate among Spanish patients hospitalized for COVID-19.

Design

Parallel pilot randomized open label, double-masked clinical trial.

Setting

University hospital setting (Reina Sofia University Hospital, Córdoba Spain.)

Participants

76 consecutive patients hospitalized with COVID-19 infection, clinical picture of acute respiratory infection, confirmed by a radiographic pattern of viral pneumonia and by a positive SARS-CoV-2 PCR with CURB65 severity scale (recommending hospital admission in case of total score > 1).

Procedures

All hospitalized patients received as best available therapy the same standard care, (per hospital protocol), of a combination of hydroxychloroquine (400 mg every 12 h on the first day, and 200 mg every 12 h for the following 5 days), azithromycin (500 mg orally for 5 days. Eligible patients were allocated at a 2 calcifediol:1 no calcifediol ratio through electronic randomization on the day of admission to take oral calcifediol (0.532 mg), or not. Patients in the calcifediol treatment group continued with oral calcifediol (0.266 mg) on day 3 and 7, and then weekly until discharge or ICU admission. Outcomes of effectiveness included rate of ICU admission and deaths.

Results

Of 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %) p value X2 Fischer test p < 0.001. Univariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment versus without Calcifediol treatment: 0.02 (95 %CI 0.002?0.17). Multivariate Risk Estimate Odds Ratio for ICU in patients with Calcifediol treatment vs Without Calcifediol treatment ICU (adjusting by Hypertension and T2DM): 0.03 (95 %CI: 0.003-0.25). Of the patients treated with calcifediol, none died, and all were discharged, without complications. The 13 patients not treated with calcifediol, who were not admitted to the ICU, were discharged. Of the 13 patients admitted to the ICU, two died and the remaining 11 were discharged.

Conclusion

Our pilot study demonstrated that administration of a high dose of Calcifediol or 25-hydroxyvitamin D, a main metabolite of vitamin D endocrine system, significantly reduced the need for ICU treatment of patients requiring hospitalization due to proven COVID-19. Calcifediol seems to be able to reduce severity of the disease, but larger trials with groups properly matched will be required to show a definitive answer.

Keywords

COVID-19
SARS-CoV-2
Vitamin D
Vitamin D3 or cholecalciferol
Calcifediol or 25-hydroxyvitamin D3
1α, 25(OH)2D or 1α, 25-dihydroxyvitamin D or calcitriol
Acute respiratory distress syndrome (ARDS)
Cytokine/Chemokine storm
Renin-angiotensin system
Hypercoagulability
Hydroxychloroquine
Chloroquine
Covidiol
Neutrophil activity
Vitamin D endocrine system
Cuboidal alveolar coating cells type II
Cathelicidin peptide
Defensins
TLR co-receptor CD14
Vitamin D receptor
View Abstract