Treatment With 25-Hydroxyvitamin D3 (Calcifediol) Is Associated With a Reduction in the Blood Neutrophil-to-Lymphocyte Ratio Marker of Disease Severity in Hospitalized Patients With COVID-19: A Pilot Multicenter, Randomized, Placebo-Controlled, Double-Blinded Clinical Trial

Abstract

Objective: The goal of this randomized, double-blinded, placebo-controlled clinical trial was to investigate the therapeutic efficacy of oral 25-hydroxyvitamin D₃ (25(OH)D₃) in improving vitamin D status in vitamin D-deficient/vitamin D-insufficient patients infected with the SARS-CoV-2 (COVID-19) virus.

Methods: This is a multicenter, randomized, double-blinded, placebo-controlled clinical trial. Participants were recruited from 3 hospitals that are affiliated to [Institution Blinded for Review] and [Institution Blinded for Review].

Results: A total 106 hospitalized patients who had a circulating 25(OH)D₃ concentration of <30 ng/mL were enrolled in this study. Within 30 and 60 days, 76.4% (26 of 34) and 100% (24 of 24) of the patients who received 25(OH)D₃ had a sufficient circulating 25(OH)D₃ concentration, whereas ≤12.5% of the patients in the placebo group had a sufficient circulating 25(OH)D₃ concentration during the 2-month follow-up. We observed an overall lower trend for hospitalization, intensive care unit duration, need for ventilator assistance, and mortality in the 25(OH)D₃ group compared with that in the placebo group, but differences were not statistically significant. Treatment with oral 25(OH)D₃ was associated with a significant increase in the lymphocyte percentage and decrease in the neutrophil-to-lymphocyte ratio in the patients. The lower neutrophil-to-lymphocyte ratio was significantly associated with reduced intensive care unit admission days and mortality.

Conclusion: Our analysis indicated that oral 25(OH)D₃ was able to correct vitamin D deficiency/insufficiency in patients with COVID-19 that resulted in improved immune function by increasing blood lymphocyte percentage. Randomized controlled trials with a larger sample size and higher dose of 25(OH)D₃ may be needed to confirm the potential effect of 25(OH)D₃ on reducing clinical outcomes in patients with COVID-19.

Keywords: 25-hydroxyvitamin D(3); COVID-19; lymphocyte; supplementation; viral infection; vitamin D deficiency.