Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19.

BACKGROUND AND OBJECTIVES

The Coronavirus disease 2019 (COVID-19) pandemic underscored the importance of identifying host factors that influence susceptibility to infection. Vitamin D signaling, mediated via its receptor (), along with innate immune mediators such as antimicrobial peptides (e.g., ) and inflammatory chemokines (e.g., ), plays a critical role in antiviral defense. This study aimed to determine how serum vitamin D status and gene expression of , , and associate with COVID-19 risk in a Lebanese cohort.

METHODS

This prospective observational study assessed serum vitamin D concentrations and nasopharyngeal gene expression in Lebanese participants tested for SARS-CoV-2 between January and March 2024. We enrolled 264 patients undergoing RT-qPCR (targeting , , and genes) and quantified serum 25-hydroxyvitamin D [25(OH)D]. In a subset of 70 individuals stratified by COVID-19 status, we measured , , , and expression by RT-qPCR. Multiple logistic regression and Pearson correlation analyses were performed.

RESULTS

Serum vitamin D levels and expression were not significantly associated with COVID-19 status. Elevated expression in nasopharyngeal tissue correlated with lower COVID-19 risk (OR = 0.40, = 0.05) and inversely with 25(OH)D levels (r = -0.61, = 0.04). Higher expression reduced COVID-19 risk by 81.6% (OR = 0.184, = 0.012). Among COVID-19 negatives, correlated with (r = 0.59, < 0.01); among positives, correlated with (r = 0.45, < 0.05).

CONCLUSION

Our findings reveal a complex interplay between systemic vitamin D status, local VDR expression, and innate inflammatory mediators in COVID-19. They support a model in which both micronutrient levels and tissue-specific vitamin D signaling modulate host susceptibility and disease severity.

Copyright © 2025 Missilmani, Maarabouni, Salem-Sokhn, Karras, Fakhoury and El Shamieh.