{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,19]],"date-time":"2026-07-19T04:13:48Z","timestamp":1784434428977,"version":"3.55.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T00:00:00Z","timestamp":1755561600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background and objectives<\/jats:title><jats:p>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 (<jats:italic>VDR<\/jats:italic>), along with innate immune mediators such as antimicrobial peptides (e.g., <jats:italic>DEFA1-3<\/jats:italic>) and inflammatory chemokines (e.g., <jats:italic>CCL20<\/jats:italic>), plays a critical role in antiviral defense. This study aimed to determine how serum vitamin D status and gene expression of <jats:italic>VDR<\/jats:italic>, <jats:italic>DEFA1-3<\/jats:italic>, and <jats:italic>CCL20<\/jats:italic> associate with COVID-19 risk in a Lebanese cohort.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>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 <jats:italic>ORF1<\/jats:italic>, <jats:italic>N<\/jats:italic>, and <jats:italic>E<\/jats:italic> genes) and quantified serum 25-hydroxyvitamin D [25(OH)D]. In a subset of 70 individuals stratified by COVID-19 status, we measured <jats:italic>VDR<\/jats:italic>, <jats:italic>DEFA1-3<\/jats:italic>, <jats:italic>CCL20<\/jats:italic>, and <jats:italic>GAPDH<\/jats:italic> expression by RT-qPCR. Multiple logistic regression and Pearson correlation analyses were performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Serum vitamin D levels and <jats:italic>CCL20<\/jats:italic> expression were not significantly associated with COVID-19 status. Elevated <jats:italic>VDR<\/jats:italic> expression in nasopharyngeal tissue correlated with lower COVID-19 risk (OR = 0.40, <jats:italic>p<\/jats:italic> = 0.05) and inversely with 25(OH)D levels (r = \u20130.61, <jats:italic>p<\/jats:italic> = 0.04). Higher <jats:italic>DEFA1\u20133<\/jats:italic> expression reduced COVID-19 risk by 81.6% (OR = 0.184, <jats:italic>p<\/jats:italic> = 0.012). Among COVID-19 negatives, <jats:italic>VDR<\/jats:italic> correlated with <jats:italic>CCL20<\/jats:italic> (r = 0.59, <jats:italic>p<\/jats:italic> &amp;lt; 0.01); among positives, <jats:italic>VDR<\/jats:italic> correlated with <jats:italic>DEFA1-3<\/jats:italic> (r = 0.45, <jats:italic>p<\/jats:italic> &amp;lt; 0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1600623","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T04:10:40Z","timestamp":1755576640000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19"],"prefix":"10.3389","volume":"16","author":[{"given":"Ferdos","family":"Missilmani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dima","family":"Maarabouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elie","family":"Salem-Sokhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon N.","family":"Karras","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana M. 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