Abstract

Vitamin D might play a role in counteracting COVID-19, albeit strong evidence is still lacking in the literature. The present multicenter real-practice study aimed to evaluate the differences of 25(OH)D3 serum levels in adults tested for SARS-CoV-2 (acute COVID-19 patients, subjects healed from COVID-19, and non-infected ones) recruited over a 6-month period (March–September 2021). In a sample of 117 subjects, a statistically significant difference was found, with acute COVID-19 patients demonstrating the lowest levels of serum 25(OH)D3 (9.63 ± 8.70 ng/mL), significantly lower than values reported by no-COVID-19 patients (15.96 ± 5.99 ng/mL, p = 0.0091) and healed COVID-19 patients (11.52 ± 4.90 ng/mL, p > 0.05). Male gender across the three groups displayed unfluctuating 25(OH)D3 levels, hinting at an inability to ensure adequate levels of the active vitamin D3 form (1α,25(OH)2D3). As a secondary endpoint, we assessed the correlation between serum 25(OH)D3 levels and pro-inflammatory cytokine interleukin-6 (IL-6) in patients with extremely low serum 25(OH)D3 levels (<1 ng/mL) and in a subset supplemented with 1α,25(OH)2D3. Although patients with severe hypovitaminosis-D showed no significant increase in IL-6 levels, acute COVID-19 patients manifested high circulating IL-6 at admission (females = 127.64 ± 22.24 pg/mL, males = 139.28 ± 48.95 ng/mL) which dropped drastically after the administration of 1α,25(OH)2D3 (1.84 ± 0.77 pg/mL and 2.65 ± 0.92 ng/mL, respectively). Taken together, these findings suggest that an administration of 1α,25(OH)2D3 might be helpful for treating male patients with an acute COVID-19 infection. Further studies on rapid correction of vitamin D deficiency with fast acting metabolites are warranted in COVID-19 patients.

Highlights

  • The current pandemic infection of coronavirus disease 2019 (COVID-2019) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel RNA β-coronavirus that shares 79% sequence homology with SARS-CoV [1]

  • As per our primary endpoint, we evaluated the existence of a statistical difference in

  • The fact that calcitriol is formed in many tissues including immune system cells, its intracellular concentration may be higher than that found in the circulation, leading us to not assume that only those with chronic renal failure are short of calcitriol in their immune tissues. This is the first study that: (i) evaluated patients in the real-life context, without exclusion for co-morbidities; (ii) investigated the levels of vitamin D in h-COVID-19; (iii) assessed the patients in a very short time and this excluded the possibility that sun exposition could modify 25(OH)D3 levels; (iv) performed a stratification by gender; (v) proved how calcitriol can be useful in COVID-19 patients with chronic renal failure. The findings of this multicenter cross-sectional study showed insufficient 25(OH)D3 serum levels in real-life patients with and without COVID-19, and in subjects healed from COVID-19

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Summary

Introduction

The current pandemic infection of coronavirus disease 2019 (COVID-2019) is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), a novel RNA β-coronavirus that shares 79% sequence homology with SARS-CoV [1]. COVID-19, several pharmacological treatments, including vitamin D3, could negatively influence the infection progression acting on the immune system [1,2]. Both immune dysfunction and cytokine storm are involved in the development of COVID-19 [3,4]; some authors have documented that vitamin D3 is able to improve the symptoms of SARS-CoV-2 infection because it acts on the immune system and modulates lung function [3], other authors have suggested that vitamin D3 supplementation may reduce the risk of SARS-CoV-2 infection [4,5]. The first takes place in the liver and it is mediated by the 25-hydroxylase, most likely cytochrome P450 CYP2R1, which forms. The second reaction takes place in the kidney and is mediated by the 1α-hydroxylase

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