Effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in patients with moderate to severe COVID-19.
Fernandes, Alan L 1; Murai, Igor H 1; Reis, Bruna Z 1; Sales, Lucas P 1; Santos, Mayara D 1; Pinto, Ana J 6; Goessler, Karla F 6; Duran, Camila S C 1; Silva, Carla B R 1; Franco, Andre S 1; Macedo, Marina B 1, *; Dalmolin, Henrique H H 1; Baggio, Janaina 1; Balbi, Guilherme G M 1; Antonangelo, Leila 15; Caparbo, Valeria F 1; Gualano, Bruno 6, 18; Pereira, Rosa M R 1
[Article] The American Journal of Clinical Nutrition. 115(3):790-798, March 2022.

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Background: The modulating effect of vitamin D on cytokine concentrations in severe coronavirus disease 2019 (COVID-19) remains unknown.

Objectives: We aimed to investigate the effect of a single high dose of vitamin D3 on cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.

Methods: This is a post hoc, ancillary, and exploratory analysis from a multicenter, double-blind, placebo-controlled, randomized clinical trial. Patients with moderate to severe COVID-19 were recruited from 2 hospitals in Sao Paulo, Brazil. Of 240 randomly assigned patients, 200 were assessed in this study and randomly assigned to receive a single oral dose of 200,000 IU vitamin D3 (n = 101) or placebo (n = 99). The primary outcome was hospital length of stay, which has been published in our previous study. The prespecified secondary outcomes were serum concentrations of IL-1[beta], IL-6, IL-10, TNF-[alpha], and 25-hydroxyvitamin D. The post hoc exploratory secondary outcomes were IL-4, IL-12p70, IL-17A, IFN-[gamma], granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-8, IFN-inducible protein-10 (IP-10), macrophage inflammatory protein-1[beta] (MIP-1[beta]), monocyte chemoattractant protein-1 (MCP-1), vascular endothelial growth factor (VEGF), and leukocyte count. Generalized estimating equations for repeated measures, with Bonferroni's adjustment, were used for testing all outcomes.

Results: The study included 200 patients with a mean /- SD age of 55.5 /- 14.3 y and BMI of 32.2 /- 7.1 kg/m2, of which 109 (54.5%) were male. GM-CSF concentrations showed a significant group-by-time interaction effect (P = 0.04), although the between-group difference at postintervention after Bonferroni's adjustment was not significant. No significant effects were observed for the other outcomes.

Conclusions: The findings do not support the use of a single dose of 200,000 IU vitamin D3, compared with placebo, for the improvement of cytokines, chemokines, and growth factor in hospitalized patients with moderate to severe COVID-19.

This trial was registered at clinicaltrials.gov as NCT04449718.

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