Several strands of evidence have indicated that vitamin D supplementation might be helpful for COVID-19 infections. Now we also have a study testing whether it works.
Spanish researchers evaluated the effect of calcifediol treatment on Intensive Care Unit Admission and Mortality rate among patients hospitalized for COVID-19 in a randomized, double blind clinical trial. A total of 76 consecutive patients hospitalized with COVID-19 infection and 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) were included. All patients received as best available therapy the same standard care. This consisted 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 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.
Of the 50 patients treated with calcifediol, one required admission to the ICU (2%), while of 26 untreated patients, 13 required admission (50 %). 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.
The authors concluded as follows:
Our pilot study demonstrated that administration of calcifediol may improve the clinical outcome of subjects requiring hospitalization for COVID-19. Whether that would also apply to patients with an earlier stage of the disease and whether baseline vitamin D status modifies these results is unknown. Therefore, a multicenter randomized controlled trial using calcifediol, properly matched (Prevention and Treatment With Calcifediol of COVID-19 Induced Acute Respiratory Syndrome (COVIDIOL)), in 15 Spanish hospitals, funded by Clinical Research Program at COVID-19 “Progreso y Salud” Foundation and Foundation for Biomedical Research of Córdoba (FIBICO), Spain, (registered as NCT04366908 in NIH Trialnet database) will be carried out with the number of patients recalculated from the data provided by this study.
An interesting perspective of the new COVIDIOL trial with the recently available information, could be to evaluate calcifediol associated to dexamethasone or other corticoid vs. dexamethasone or other corticosteroid, since dexamethasone, which has potent anti-inflammatory actions, has recently been shown to reduce mortality in hospitalized patients on Covid-19 who are on respiratory assistance; so that treatment guidelines have been updated to recommend the use of glucocorticoids (including dexametasone), now proposed as the best available treatment in many hospitals around the world.
It is undeniable that this trial has several important limitations (and its authors are very honest to point them out). However, it is equally undeniable, in my view, that it is an important contribution to our current knowledge.