Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D3 in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial

Miguel Cervero; Daniel López-Wolf; Guiomar Casado; Maria Novella-Mena; Pablo Ryan-Murua; María Luisa Taboada-Martínez; Sara Rodríguez-Mora; Lorena Vigón; Mayte Coiras; Montserrat Torres

doi:10.3389/fphar.2022.863587

Beneficial Effect of Short-Term Supplementation of High Dose of Vitamin D₃ in Hospitalized Patients With COVID-19: A Multicenter, Single-Blinded, Prospective Randomized Pilot Clinical Trial

Front Pharmacol. 2022 Jul 4:13:863587. doi: 10.3389/fphar.2022.863587. eCollection 2022.

Affiliations

¹ Internal Medicine Service, Hospital Universitario Severo Ochoa, Leganés, Spain.
² Internal Medicine Service, Hospital Universitario Fundación Alcorcón, Alcorcón, Spain.
³ Immunopathology Unit, National Center of Microbiology, Instituto de Salud Carlos III, Madrid, Spain.
⁴ Internal Medicine Service, Hospital Universitario Príncipe de Asturias, Madrid, Spain.
⁵ Internal Medicine Service, Hospital Universitario Infanta Leonor, Madrid, Spain.
⁶ Internal Medicine Service, Hospital Universitario de Cabueñes, Gijón, Spain.

Abstract

There is now sufficient evidence to support that vitamin D deficiency may predispose to SARS-CoV-2 infection and increase COVID-19 severity and mortality. It has been suggested that vitamin D₃ supplementation may be used prophylactically as an affordable and safe strategy that could be added to the existing COVID-19 standard treatment. This multicenter, single-blinded, prospective randomized pilot clinical trial aimed to evaluate the safety, tolerability, and effectiveness of 10,000 IU/day in comparison with 2000 IU/day of cholecalciferol supplementation for 14 days to reduce the duration and severity of COVID-19 in 85 hospitalized individuals. The median age of the participants was 65 years (Interquartile range (IQR): 53-74), most of them (71%) were men and the mean baseline of 25-hydroxyvitamin D (25(OH)D) in serum was 15 ng/ml (standard deviation (SD):6). After 14 days of supplementation, serum 25(OH)D levels were significantly increased in the group who received 10,000IU/day (p < 0.0001) (n = 44) in comparison with the 2,000IU/day group (n = 41), especially in overweight and obese participants, and the higher dose was well tolerated. A fraction of the individuals in our cohort (10/85) developed acute respiratory distress syndrome (ARDS). The median length of hospital stay in these patients with ARDS was significantly different in the participants assigned to the 10,000IU/day group (n = 4; 7 days; IQR: 4-13) and the 2,000IU/day group (n = 6; 27 days; IQR: 12-45) (p = 0.04). Moreover, the inspired oxygen fraction was reduced 7.6-fold in the high dose group (p = 0.049). In terms of blood parameters, we did not identify overall significant improvements, although the platelet count showed a modest but significant difference in those patients who were supplemented with the higher dose (p = 0.0492). In conclusion, the administration of 10,000IU/day of vitamin D₃ for 14 days in association with the standard clinical care during hospitalization for COVID-19 was safe, tolerable, and beneficial, thereby helping to improve the prognosis during the recovery process.

Keywords: COVID-19; SARS-CoV-2; biochemical parameters; risk factors; vitamin D3 supplementation.