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

Background and objectivesThe 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), along with innate immune mediators such as antimicrobial peptides (e.g.,...

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Main Authors: Ferdos Missilmani, Dima Maarabouni, Elie Salem-Sokhn, Spyridon N. Karras, Hana M. A. Fakhoury, Said El Shamieh
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-08-01
Series:Frontiers in Endocrinology
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Online Access:https://www.frontiersin.org/articles/10.3389/fendo.2025.1600623/full
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author Ferdos Missilmani
Dima Maarabouni
Elie Salem-Sokhn
Spyridon N. Karras
Hana M. A. Fakhoury
Said El Shamieh
author_facet Ferdos Missilmani
Dima Maarabouni
Elie Salem-Sokhn
Spyridon N. Karras
Hana M. A. Fakhoury
Said El Shamieh
author_sort Ferdos Missilmani
collection DOAJ
description Background and objectivesThe 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), 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, DEFA1-3, and CCL20 associate with COVID-19 risk in a Lebanese cohort.MethodsThis 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, DEFA1-3, CCL20, and GAPDH expression by RT-qPCR. Multiple logistic regression and Pearson correlation analyses were performed.ResultsSerum vitamin D levels and CCL20 expression were not significantly associated with COVID-19 status. Elevated VDR 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 correlated with CCL20 (r = 0.59, p < 0.01); among positives, VDR correlated with DEFA1-3 (r = 0.45, p < 0.05).ConclusionOur 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.
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spelling doaj-art-7ea7603d89f74979b9b4a874b77b00c02025-08-20T03:44:11ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922025-08-011610.3389/fendo.2025.16006231600623Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19Ferdos Missilmani0Dima Maarabouni1Elie Salem-Sokhn2Spyridon N. Karras3Hana M. A. Fakhoury4Said El Shamieh5Molecular Testing Laboratory, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, LebanonMolecular Testing Laboratory, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, LebanonMolecular Testing Laboratory, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, LebanonLaboratory of Biological Chemistry, Medical School, Aristotle University, Thessaloniki, GreeceCollege of Medicine, Alfaisal University, Riyadh, Saudi ArabiaMolecular Testing Laboratory, Department of Medical Laboratory Sciences, Faculty of Health Sciences, Beirut Arab University, Beirut, LebanonBackground and objectivesThe 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), 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, DEFA1-3, and CCL20 associate with COVID-19 risk in a Lebanese cohort.MethodsThis 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, DEFA1-3, CCL20, and GAPDH expression by RT-qPCR. Multiple logistic regression and Pearson correlation analyses were performed.ResultsSerum vitamin D levels and CCL20 expression were not significantly associated with COVID-19 status. Elevated VDR 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 correlated with CCL20 (r = 0.59, p < 0.01); among positives, VDR correlated with DEFA1-3 (r = 0.45, p < 0.05).ConclusionOur 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.https://www.frontiersin.org/articles/10.3389/fendo.2025.1600623/fullCOVID-19vitamin DVDRinnate immunityinflammatory biomarkers
spellingShingle Ferdos Missilmani
Dima Maarabouni
Elie Salem-Sokhn
Spyridon N. Karras
Hana M. A. Fakhoury
Said El Shamieh
Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
Frontiers in Endocrinology
COVID-19
vitamin D
VDR
innate immunity
inflammatory biomarkers
title Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
title_full Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
title_fullStr Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
title_full_unstemmed Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
title_short Evaluation of vitamin D status, vitamin D receptor expression, and innate immune mediators in COVID-19
title_sort evaluation of vitamin d status vitamin d receptor expression and innate immune mediators in covid 19
topic COVID-19
vitamin D
VDR
innate immunity
inflammatory biomarkers
url https://www.frontiersin.org/articles/10.3389/fendo.2025.1600623/full
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