Calcifediol Treatment and Hospital Mortality Due to COVID-19: A Cohort Study

Abstract

Context. Calcifediol has been proposed as a potential treatment for COVID-19 patients. Objective: To compare the administration or not of oral calcifediol on mortality risk of patients hospitalized because of COVID-19. Design: Retrospective, multicenter, open, non-randomized cohort study. Settings: Hospitalized care. Patients: Patients with laboratory-confirmed COVID-19 between 5 February and 5 May 2020 in five hospitals in the South of Spain. Intervention: Patients received calcifediol (25-hydroxyvitamin D3) treatment (0.266 mg/capsule, 2 capsules on entry and then one capsule on day 3, 7, 14, 21, and 28) or not. Main Outcome Measure: In-hospital mortality during the first 30 days after admission. Results: A total of 537 patients were hospitalized with COVID-19 (317 males (59%), median age, 70 years), and 79 (14.7%) received calcifediol treatment. Overall, in-hospital mortality during the first 30 days was 17.5%. The OR of death for patients receiving calcifediol (mortality rate of 5%) was 0.22 (95% CI, 0.08 to 0.61) compared to patients not receiving such treatment (mortality rate of 20%; p < 0.01). Patients who received calcifediol after admission were more likely than those not receiving treatment to have comorbidity and a lower rate of CURB-65 score for pneumonia severity ≥ 3 (one point for each of confusion, urea > 7 mmol/L, respiratory rate ≥ 30/min, systolic blood pressure < 90 mm Hg or diastolic blood pressure ≤ 60 mm Hg, and age ≥ 65 years), acute respiratory distress syndrome (moderate or severe), c-reactive protein, chronic kidney disease, and blood urea nitrogen. In a multivariable logistic regression model, adjusting for confounders, there were significant differences in mortality for patients receiving calcifediol compared with patients not receiving it (OR = 0.16 (95% CI 0.03 to 0.80). Conclusion: Among patients hospitalized with COVID-19, treatment with calcifediol, compared with those not receiving calcifediol, was significantly associated with lower in-hospital mortality during the first 30 days. The observational design and sample size may limit the interpretation of these findings.

Vitamin D supplementation and clinical outcomes in COVID-19: a systematic review and meta-analysis

“…After a scrupulous literature search and a meticulous study selection process, we included 13 studies in the present meta-analysis [7][8][9][10][11][12][13][14][15][22][23][24][25], pooling data retrieved from 2933 patients with COVID-19 (Fig. 1).…”

“…Five studies catered to the use of vitamin D before the diagnosis of COVID-19 [9,12,14,23,24], while seven studies had reported the use of vitamin D after the diagnosis of COVID-19 [7,10,11,13,15,22,25]. Annweiler et al [8] had considered the use of oral cholecalciferol in the week following the suspicion or diagnosis of COVID-19 or during the previous month.…”

“…The majority of the studies had used oral cholecalciferol, while Entrenas Castillo et al [11] and Alcala-Diaz et al [22] had used oral calcifediol. The dose of cholecalciferol used was highly variable across the included studies, ranging from 80,000 IU within a few hours of diagnosis of COVID-19 to a maximum of 400,000 IU supplemented as bolus oral cholecalciferol daily for 2 consecutive days (the second and third day of the in-hospital stay) [7,10].…”

Lung-Centric Inflammation of COVID-19: Potential Modulation by Vitamin D

“…A recent meta-analysis indicates that low levels of vitamin D (20–30 ng/mL) are associated with a greater susceptibility to SARS-CoV-2 infection, as well as severity and mortality of COVID-19 [ 62 ]. Conversely, in a multicenter retrospective study, supplemental 25-OHD during the first month of hospitalization reduced in-hospital mortality [ 63 ]. Thus, it is not surprising that vitamin D has been touted as a potential therapeutic adjunct to conventional approaches in the treatment of COVID-19 [ 56 , 57 , 60 , 64 ].…”

“…To this end, the PubMed database was mined for vitamin D/VDR data relevant to the aberrant immune response of COVID-19 and yielded the following. Studies addressing the prophylactic or therapeutic efficacy of vitamin D for the ARDS of COVID-19 are limited [ 57 , 63 , 65 , 66 , 67 ]. A transgenic murine model of COVID-19 that mimics the disease in humans is available [ 68 , 69 ]; however, it has not been used for interventional studies of vitamin D/VDR signaling.…”