Evaluation of Vitamin D Status, Vitamin D Receptor Expression, and Innate Immune Mediators in COVID-19

Ferdos Missilmani¹Dima Maarabouni¹Elie Salem-Sokhn¹Spyridon N. Karras²Hana M.A. Fakhoury^3*Said El Shamieh^1*

• ¹Department of Medical Laboratory Technology, Faculty of Health Sciences, Beirut Arab University, Beirut, Lebanon
• ²Laboratory of Biological Chemistry Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece
• ³Alfaisal University, Riyadh, Saudi Arabia

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 (VDR-1), along with innate immune mediators such as antimicrobial peptides (e.g., DEFA1-3) and inflammatory chemokines (e.g., CCL20), plays a critical role in antiviral defense. This study aimed to determine how serum vitamin D status and gene expression of VDR-1, DEFA1-3, and CCL20 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 ORF1, N, and E genes) and quantified serum 25-hydroxyvitamin D [25(OH)D]. In a subset of 70 individuals stratified by COVID-19 status, we measured VDR-1, DEFA1-3, CCL20, and GAPDH expression by RT-qPCR. Multiple logistic regression and Pearson correlation analyses were performed. Results: Serum vitamin D levels and CCL20 expression were not significantly associated with COVID-19 status. Elevated VDR-1 expression in nasopharyngeal tissue correlated with lower COVID-19 risk (OR = 0.40, p = 0.05) and inversely with 25(OH)D levels (r = -0.61, p = 0.04).Higher DEFA1-3 expression reduced COVID-19 risk by 81.6% (OR = 0.184, p = 0.012).Among COVID-19 negatives, VDR-1 correlated with CCL20 (r = 0.59, p < 0.01); among positives, VDR-1 correlated with DEFA1-3 (r = 0.45, p < 0.05).Our findings reveal a complex interplay between systemic vitamin D status, local VDR-1 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.