Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression
et al., The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2025.106879, Jan 2026
Vitamin D for COVID-19
8th treatment shown to reduce risk in
October 2020, now with p < 0.00000000001 from 136 studies, recognized in 18 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,400+ studies for
210+ treatments. c19early.org
|
Prospective case-control study of 95 COVID-19 patients and 75 healthy controls in Iraq showing strong associations between vitamin D deficiency, VDR gene polymorphism, and COVID-19 severity and mortality.
Awla et al., 31 Jan 2026, prospective, Iraq, peer-reviewed, 9 authors, study period 4 May, 2021 - 4 October, 2021.
Contact: harem.awla@su.edu.krd, drbaghawanjaff@gmail.com, dawan.rafeeq@koyauniversity.org, smail@su.edu.krd, raya.yashooa@uohamdaniya.edu.iq, asmaa.ameen@cihanuniversity.edu.iq, shwann.pharma@gmail.com, christer.janson@medsci.uu.se.
Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression
The Journal of Steroid Biochemistry and Molecular Biology, doi:10.1016/j.jsbmb.2025.106879
Background: Vitamin D is a known immunomodulator, but its predictive value in COVID-19 remains incompletely understood. This study investigates the role of vitamin D across molecular, biochemical, and histopathological levels to evaluate its association with COVID-19 severity and mortality. Methods: A prospective case-control study was conducted in the Kurdistan Region of Iraq from May to October 2021. Ninety-five confirmed COVID-19 patients (75 survivors, 20 non-survivors) and 75 healthy controls were enrolled. Serum 25(OH)D levels were quantified by ELISA. Clinical severity was assessed using CURB-65, NEWS, and SOFA scores. Genotyping for the FokI (rs2228570) polymorphism in the VDR gene was performed via allelespecific PCR. Lung tissue from five survivors (biopsy) and five non-survivors (autopsy) underwent immunohistochemical staining to evaluate VDR expression. Results: Serum vitamin D concentrations were markedly reduced in non-survivors (20.34 ± 0.46 ng/mL) relative to survivors (40.11 ± 0.28 ng/mL, p < 0.001). Vitamin D exhibited a negative correlation with CURB-65 (r = -0.828), NEWS (r = -0.794), and SOFA (r = -0.762) scores. Regression analysis established that vitamin D was independently associated with disease severity in our population. The TT genotype of the FokI VDR polymorphism correlated with markedly reduced vitamin D levels and elevated severity scores. Mortality exhibited a strong association with the TT genotype (OR = 10.29, 95 % CI: 2.204-49.19, p = 0.003) and the T allele (OR = 3.923, p = 0.0006). ROC analysis determined a vitamin D threshold of ≤ 20.56 ng/mL as indicative of mortality (AUC = 0.784, p < 0.0001). Immunohistochemistry demonstrated elevated VDR expression in lung tissues of deceased COVID-19 patients relative to VDR-negative controls. Conclusion: This study indicates that serum vitamin D levels, VDR gene polymorphism (rs2228570), and lung tissue VDR expression are strongly correlated with the severity and mortality of COVID-19. These findings validate the clinical use of vitamin D and VDR profiling may have associative markers and prospective treatment targets in the management of COVID-19.
Ethical Approval and Informed Consent The study protocol received ethical clearance from the University of Salahaddin's Ethical Committee (approval number SU-RE/2021/119) in March 2021. All procedures adhered strictly to the Declaration of Helsinki. Written informed consent was obtained from all participants or, where patients were incapacitated, from their legally authorized representatives.
Author contributions Harem Khdir Awla contributed to the conceptualization of the study, methodology design, data curation, and drafting of the original manuscript. Baghawan Ahmed Othman was responsible for statistical analysis, data interpretation, and figure preparation. Dawan Dlshad Rafeeq carried out the experimental procedures, including sample processing and data collection. Shukur Wasman Smail supervised the overall project, contributed to study design, critically reviewed the manuscript, and approved the final version for submission. Raya Kh. Yashooa participated in literature review, data validation, and assisted in manuscript editing. Asmaa Ameen Ghareeb supported laboratory work, data entry, and logistical coordination. Rebaz Hamza Salih and Shwan Ali Omar were involved in clinical evaluation, patient recruitment, and ensured adherence to ethical standards. Christer Janson provided expert consultation on study design and interpretation of findings, and contributed to the critical revision of the manuscript for important intellectual content.
CRediT authorship contribution..
References
Abbas, Salloom, Misha, Taqi, Vitamin d receptor rs2228570 and rs1544410 genetic polymorphisms frequency in Iraqi thalassemia patients compared to other ethnic populations, Gene Rep
Abdalfatah, Shareef, Saleh, Rajab, Smail et al., The association of VDR/fokI gene polymorphism and protein expression with histopathological alterations in patients with thyroid colloid nodule, Anal Cell Pathol (Amst)
Adams, Hewison, Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity, Nat. Clin. Pr. Endocrinol. Metab
Al-Daghri, Amer, Alotaibi, Aldisi, Enani et al., Vitamin d status of arab gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study, J. Transl. Med
Alguwaihes, Sabico, Hasanato, Al-Sofiani, Megdad et al., Severe vitamin d deficiency is not related to SARS-CoV-2 infection but May increase mortality risk in hospitalized adults: a retrospective case-control study in an arab gulf country, Aging Clin. Exp. Res
Alhammadin, Jarrar, Madani, Lee, Exploring the influence of VDR genetic variants taqI, apaI, and fokI on COVID-19 severity and long-COVID-19 symptoms, J. Pers. Med
Amrein, Scherkl, Hoffmann, Neuwersch-Sommeregger, Köstenberger et al., Vitamin d deficiency 2.0: an update on the current status worldwide, Eur. J. Clin. Nutr
Apaydin, Polat, Dincer Yazan, Ilgin, Elbasan et al., Effects of vitamin d receptor gene polymorphisms on the prognosis of COVID-19, Clin. Endocrinol
Aranow, Vitamin d and the immune system, J. Invest. Med
Ashique, Gupta, Gupta, Mishra, Singh et al., Vitamin D-A prominent immunomodulator to prevent COVID-19 infection, Int. J. Rheum. Dis
Bikle, Vitamin d regulation of immune function during covid-19, Rev. Endocr. Metab. Disord
Biswas, Rahaman, Biswas, Haque, Ibrahim, Association of sex, age, and comorbidities with mortality in COVID-19 patients: a systematic review and meta-analysis, Intervirology
Bossuyt, Reitsma, Bruns, Gatsonis, Glasziou et al., an updated list of essential items for reporting diagnostic accuracy studies, BMJ
Bradley, Sbaih, Chandler, Furmanek, Ramirez et al., Pneumonia severity index and CURB-65 score are good predictors of mortality in hospitalized patients with SARS-CoV-2 Community-Acquired pneumonia, Chest
Button, Ioannidis, Mokrysz, Nosek, Flint et al., Power failure: why small sample size undermines the reliability of neuroscience, Nat. Rev. Neurosci
Cashman, Dowling, Škrabáková, Gonzalez-Gross, Valtueña et al., Vitamin d deficiency in Europe: pandemic?, Am. J. Clin. Nutr
Ciotti, Ciccozzi, Terrinoni, Jiang, Wang et al., The COVID-19 pandemic, Crit. Rev. Clin. Lab Sci
Cohen, Statistical power analysis for the behavioral sciences
Contes, Liu, Epidemiology, clinical significance, and diagnosis of respiratory viruses and their Co-Infections in the Post-COVID era, Pathogens
Enzel, Kriventsov, Sataieva, Malygina, Cellular and molecular genetic mechanisms of lung fibrosis development and the role of vitamin D: a review, Int J. Mol. Sci
Faul, Erdfelder, Lang, Buchner, G* power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences, Behav. Res Methods
Ghasemian, Shamshirian, Heydari, Malekan, Alizadeh-Navaei et al., The role of vitamin d in the age of COVID-19: a systematic review and meta-analysis, Int. J. Clin. Pract
Giner-Sorolla, Montoya, Reifman, Carpenter, Lewis et al., Power to detect what? Considerations for planning and evaluating sample size, Pers. Soc. Psychol. Rev
Grant, Lahore, Mcdonnell, Baggerly, French et al., Evidence that vitamin d supplementation could reduce risk of influenza and COVID-19 infections and deaths, Nutrients
Harvey, Burne, Mcgrath, Eyles, Developmental vitamin D3 deficiency induces alterations in immune organ morphology and function in adult offspring, J. Steroid Biochem Mol. Biol
Hattersley, Mccarthy, What makes a good genetic association study?, Lancet
Horner, Ambrose, Taylor, Erinle, Intensive care society state of the art (SOA) 2023 Congress abstracts, J. Intensive Care Soc
Ioannidis, Trikalinos, Ntzani, Contopoulos-Ioannidis, Genetic associations in large versus small studies: an empirical assessment, Lancet
Jafari, Pirouzi, Anoosheh, Farnia, Tajik, Rapid and simultaneous detection of vitamin d receptor gene polymorphisms by a single ARMS-PCR assay, Mol. Diagn. Ther
Jafari-Vayghan, Rahimlou, Almasi-Hashiani, Aframehr, Saleh-Ghadimi, Effect of the vitamin d supplementation on clinical outcomes and inflammatory status in COVID-19 patients: an umbrella review, BMC Nutr
Katz, Yue, Xue, Increased risk for COVID-19 in patients with vitamin d deficiency, Nutrition
Kilic, Halu, De Marzio, Maiorino, Duvall et al., Vitamin d constrains inflammation by modulating the expression of key genes on Chr17q12-21, Elife
Kongsbak, Levring, Geisler, Von Essen, The vitamin d receptor and t cell function, Front Immunol
Kumar, Himani, Gupta, Singh, Kumar et al., Unveiling molecular associations of polymorphic variants of VDR gene (fokI, bsmI and apaI) in multiple myeloma patients of Indian population, J. Steroid Biochem Mol. Biol
Kılınç Toker, Çelik, Toker, Eren, Quick COVID-19 severity index, CURB-65 and quick SOFA scores comparison in predicting mortality and risk factors of COVID-19 patients, Arch. Iran. Med
Larysz, Recław, Suchanecka, Dziurawiec, Tkacz et al., Vitamin d genetics beyond serum 25 (OH) D: VDR rs2228570 (fokI) polymorphism, inflammation, and quality of life in orthopedic patients, Nutrients
Libertini, Corbi, Shubernetskaya, Komici, Ferrara, Diseases deriving from alterations of the ecological Niche-Part I: not regarding the holobiont
Lim, Van Der Eerden, Laing, Boersma, Karalus et al., Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study, Thorax
Liu, Stenger, Li, Wenzel, Tan et al., Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response, Science
Majed, Dzay, Yashooa, Mustafa, Outbreak of SARS-CoV-2 variants in Iraqi kurdistan region, J. Infect. Dev. Ctries
Matilainen, Räsänen, Gynther, Väisänen, The genes encoding cytokines IL-2, IL-10 and IL-12B are primary 1alpha,25(OH)2D3 target genes, J. Steroid Biochem Mol. Biol
Merzon, Tworowski, Gorohovski, Vinker, Golan Cohen et al., Low plasma 25 (OH) vitamin d level is associated with increased risk of COVID-19 infection: an Israeli population-based study, FEBS J
Missilmani, Maarabouni, Salem-Sokhn, Karras, Fakhoury et al., Evaluation of vitamin d status, vitamin d receptor expression, and innate immune mediators in COVID-19, Front Endocrinol
Mohamed, Alanazi, Ahmed, Elfiky, Ghafar et al., FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children, Cytokine
Noh, Chow, Quach, Groothuis, Tirona et al., Significance of the vitamin d receptor on crosstalk with nuclear receptors and regulation of enzymes and transporters, Aaps J
Ochoa-Ramírez, Corona-Angulo, Ríos-Burgueño, Sánchez-Zazueta, Becerra-Loaiza et al., Vitamin d receptor gene polymorphisms role in COVID-19 severity: results of a Mexican patients' cohort, Int J. Immunogenet
Pandey, Kajal, Mishra, Vitamin d and influenza: immunological insights and therapeutic potential for respiratory health, Nutr. Rev
Pepe, Janes, Longton, Leisenring, Newcomb, Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker, Am. J. Epidemiol
Sabico, Enani, Sheshah, Aljohani, Aldisi et al., Effects of a 2-Week 5000 IU versus 1000 IU vitamin D3 supplementation on recovery of symptoms in patients with mild to moderate Covid-19: a randomized clinical trial, Nutrients
Sartini, Del Puente, Carbone, Schinca, Ottria et al., The effect of vitamin d supplementation post COVID-19 infection and related outcomes: a systematic review and Meta-Analysis, Nutrients
Score, 2: standardising the assessment of acute-illness severity in the NHS, updated report of a working party
Soo, Zuege, Fick, Niven, Berthiaume et al., Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients, Crit. care (Lond. Engl. )
Teasdale, Maas, Lecky, Manley, Stocchetti et al., The glasgow coma scale at 40 years: standing the test of time, Lancet Neurol
Turner, Bird, Higgins, The impact of study size on meta-analyses: examination of underpowered studies in cochrane reviews, PloS One
Vincent, Moreno, Takala, Willatts, De Mendonça et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on Sepsis-Related problems of the european society of intensive care Medicine, Intensive Care Med
Vincent, Moreno, Takala, Willatts, De Mendonça et al., The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the working group on Sepsis-Related problems of the european society of intensive care Medicine (see contributors to the project in the appendix), Intensive Care Med
Voiculescu, Nelson Twakor, Jerpelea, Pantea Stoian, Vitamin D: beyond traditional Roles-Insights into its biochemical pathways and physiological impacts, Nutrients
Wahl, Cooper, Ebeling, Eggersdorfer, Hilger et al., A global representation of vitamin d status in healthy populations, Arch. Osteoporos
Waldron, Ashby, Cornes, Bechervaise, Razavi et al., Vitamin D: a negative acute phase reactant, J. Clin. Pathol
Williams, Alberti, Ball, Royal college for physicians: national early warning score (NEWS): standardising the assessment of Acute-Illness severity in the NHS
Williams, The National early warning score: from concept to NHS implementation, Clin. Med
Zeidan, Lateef, Selim, Razek, Abd-Elrehim et al., Vitamin d deficiency and vitamin d receptor fokI polymorphism as risk factors for COVID-19, Pedia Res
Zhao, Ye, Liu, Zhang, Park et al., Research waste in temporomandibular disorders among registered randomised controlled trials: a Meta-Epidemiologic study, J. Oral. Rehabil
Zhu, Zhang, Li, Zou, Bing et al., Vitamin d supplementation for managing COVID-19 in patients with vitamin d deficiency: a systematic review and meta-analysis of randomised controlled trials, BMJ Open
DOI record:
{
"DOI": "10.1016/j.jsbmb.2025.106879",
"ISSN": [
"0960-0760"
],
"URL": "http://dx.doi.org/10.1016/j.jsbmb.2025.106879",
"alternative-id": [
"S0960076025002079"
],
"article-number": "106879",
"assertion": [
{
"label": "This article is maintained by",
"name": "publisher",
"value": "Elsevier"
},
{
"label": "Article Title",
"name": "articletitle",
"value": "Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression"
},
{
"label": "Journal Title",
"name": "journaltitle",
"value": "The Journal of Steroid Biochemistry and Molecular Biology"
},
{
"label": "CrossRef DOI link to publisher maintained version",
"name": "articlelink",
"value": "https://doi.org/10.1016/j.jsbmb.2025.106879"
},
{
"label": "Content Type",
"name": "content_type",
"value": "article"
},
{
"label": "Copyright",
"name": "copyright",
"value": "© 2025 The Author(s). Published by Elsevier Ltd."
}
],
"author": [
{
"affiliation": [],
"family": "Awla",
"given": "Harem Khdir",
"sequence": "first"
},
{
"affiliation": [],
"family": "Othman",
"given": "Baghawan Ahmed",
"sequence": "additional"
},
{
"affiliation": [],
"family": "rafeeq",
"given": "Dawan dlshad",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Smail",
"given": "Shukur Wasman",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Yashooa",
"given": "Raya Kh.",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Ghareeb",
"given": "Asmaa Ameen",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Salih",
"given": "Rebaz Hamza",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Omar",
"given": "Shwan Ali",
"sequence": "additional"
},
{
"affiliation": [],
"family": "Janson",
"given": "Christer",
"sequence": "additional"
}
],
"container-title": "The Journal of Steroid Biochemistry and Molecular Biology",
"container-title-short": "The Journal of Steroid Biochemistry and Molecular Biology",
"content-domain": {
"crossmark-restriction": true,
"domain": [
"elsevier.com",
"sciencedirect.com"
]
},
"created": {
"date-parts": [
[
2025,
10,
23
]
],
"date-time": "2025-10-23T01:49:44Z",
"timestamp": 1761184184000
},
"deposited": {
"date-parts": [
[
2026,
1,
29
]
],
"date-time": "2026-01-29T15:58:29Z",
"timestamp": 1769702309000
},
"funder": [
{
"DOI": "10.13039/501100020034",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100020034",
"id-type": "DOI"
}
],
"name": "Bror Hjerpstedts stiftelse"
},
{
"DOI": "10.13039/501100007051",
"doi-asserted-by": "publisher",
"id": [
{
"asserted-by": "publisher",
"id": "10.13039/501100007051",
"id-type": "DOI"
}
],
"name": "Uppsala University"
}
],
"indexed": {
"date-parts": [
[
2026,
1,
30
]
],
"date-time": "2026-01-30T06:17:13Z",
"timestamp": 1769753833811,
"version": "3.49.0"
},
"is-referenced-by-count": 0,
"issued": {
"date-parts": [
[
2026,
1
]
]
},
"language": "en",
"license": [
{
"URL": "https://www.elsevier.com/tdm/userlicense/1.0/",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
1,
1
]
],
"date-time": "2026-01-01T00:00:00Z",
"timestamp": 1767225600000
}
},
{
"URL": "https://www.elsevier.com/legal/tdmrep-license",
"content-version": "tdm",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2026,
1,
1
]
],
"date-time": "2026-01-01T00:00:00Z",
"timestamp": 1767225600000
}
},
{
"URL": "http://creativecommons.org/licenses/by/4.0/",
"content-version": "vor",
"delay-in-days": 0,
"start": {
"date-parts": [
[
2025,
10,
22
]
],
"date-time": "2025-10-22T00:00:00Z",
"timestamp": 1761091200000
}
}
],
"link": [
{
"URL": "https://api.elsevier.com/content/article/PII:S0960076025002079?httpAccept=text/xml",
"content-type": "text/xml",
"content-version": "vor",
"intended-application": "text-mining"
},
{
"URL": "https://api.elsevier.com/content/article/PII:S0960076025002079?httpAccept=text/plain",
"content-type": "text/plain",
"content-version": "vor",
"intended-application": "text-mining"
}
],
"member": "78",
"original-title": [],
"page": "106879",
"prefix": "10.1016",
"published": {
"date-parts": [
[
2026,
1
]
]
},
"published-print": {
"date-parts": [
[
2026,
1
]
]
},
"publisher": "Elsevier BV",
"reference": [
{
"DOI": "10.1080/10408363.2020.1783198",
"article-title": "The COVID-19 pandemic",
"author": "Ciotti",
"doi-asserted-by": "crossref",
"first-page": "365",
"journal-title": "Crit. Rev. Clin. Lab Sci.",
"key": "10.1016/j.jsbmb.2025.106879_bib1",
"volume": "57",
"year": "2020"
},
{
"DOI": "10.3855/jidc.19351",
"article-title": "Outbreak of SARS-CoV-2 variants in Iraqi kurdistan region",
"author": "Majed",
"doi-asserted-by": "crossref",
"first-page": "S73",
"journal-title": "J. Infect. Dev. Ctries",
"key": "10.1016/j.jsbmb.2025.106879_bib2",
"volume": "18",
"year": "2024"
},
{
"DOI": "10.3390/pathogens14030262",
"article-title": "Epidemiology, clinical significance, and diagnosis of respiratory viruses and their Co-Infections in the Post-COVID era",
"author": "Contes",
"doi-asserted-by": "crossref",
"first-page": "262",
"journal-title": "Pathogens",
"key": "10.1016/j.jsbmb.2025.106879_bib3",
"volume": "14",
"year": "2025"
},
{
"DOI": "10.1159/000512592",
"article-title": "Association of sex, age, and comorbidities with mortality in COVID-19 patients: a systematic review and meta-analysis",
"author": "Biswas",
"doi-asserted-by": "crossref",
"first-page": "36",
"journal-title": "Intervirology",
"key": "10.1016/j.jsbmb.2025.106879_bib4",
"volume": "64",
"year": "2021"
},
{
"DOI": "10.1016/j.nut.2020.111106",
"article-title": "Increased risk for COVID-19 in patients with vitamin d deficiency",
"author": "Katz",
"doi-asserted-by": "crossref",
"journal-title": "Nutrition",
"key": "10.1016/j.jsbmb.2025.106879_bib5",
"volume": "84",
"year": "2021"
},
{
"DOI": "10.3390/nu12040988",
"article-title": "Evidence that vitamin d supplementation could reduce risk of influenza and COVID-19 infections and deaths",
"author": "Grant",
"doi-asserted-by": "crossref",
"first-page": "988",
"journal-title": "Nutrients",
"key": "10.1016/j.jsbmb.2025.106879_bib6",
"volume": "12",
"year": "2020"
},
{
"DOI": "10.1111/ijcp.14675",
"article-title": "The role of vitamin d in the age of COVID-19: a systematic review and meta-analysis",
"author": "Ghasemian",
"doi-asserted-by": "crossref",
"journal-title": "Int. J. Clin. Pract.",
"key": "10.1016/j.jsbmb.2025.106879_bib7",
"volume": "75",
"year": "2021"
},
{
"article-title": "Vitamin d and influenza: immunological insights and therapeutic potential for respiratory health",
"author": "Pandey",
"journal-title": "Nutr. Rev.",
"key": "10.1016/j.jsbmb.2025.106879_bib8",
"year": "2025"
},
{
"DOI": "10.3390/ijms25168946",
"article-title": "Cellular and molecular genetic mechanisms of lung fibrosis development and the role of vitamin D: a review",
"author": "Enzel",
"doi-asserted-by": "crossref",
"first-page": "8946",
"journal-title": "Int J. Mol. Sci.",
"key": "10.1016/j.jsbmb.2025.106879_bib9",
"volume": "25",
"year": "2024"
},
{
"DOI": "10.3390/nu17050803",
"article-title": "Vitamin D: beyond traditional Roles—Insights into its biochemical pathways and physiological impacts",
"author": "Voiculescu",
"doi-asserted-by": "crossref",
"first-page": "803",
"journal-title": "Nutrients",
"key": "10.1016/j.jsbmb.2025.106879_bib10",
"volume": "17",
"year": "2025"
},
{
"DOI": "10.2310/JIM.0b013e31821b8755",
"article-title": "Vitamin d and the immune system",
"author": "Aranow",
"doi-asserted-by": "crossref",
"first-page": "881",
"journal-title": "J. Invest. Med",
"key": "10.1016/j.jsbmb.2025.106879_bib11",
"volume": "59",
"year": "2011"
},
{
"DOI": "10.1208/s12248-022-00719-9",
"article-title": "Significance of the vitamin d receptor on crosstalk with nuclear receptors and regulation of enzymes and transporters",
"author": "Noh",
"doi-asserted-by": "crossref",
"first-page": "71",
"journal-title": "Aaps J.",
"key": "10.1016/j.jsbmb.2025.106879_bib12",
"volume": "24",
"year": "2022"
},
{
"DOI": "10.3389/fimmu.2013.00148",
"article-title": "The vitamin d receptor and t cell function",
"author": "Kongsbak",
"doi-asserted-by": "crossref",
"first-page": "148",
"journal-title": "Front Immunol.",
"key": "10.1016/j.jsbmb.2025.106879_bib13",
"volume": "4",
"year": "2013"
},
{
"DOI": "10.3389/fendo.2025.1600623",
"article-title": "Evaluation of vitamin d status, vitamin d receptor expression, and innate immune mediators in COVID-19",
"author": "Missilmani",
"doi-asserted-by": "crossref",
"first-page": "1600623",
"journal-title": "Front Endocrinol.",
"key": "10.1016/j.jsbmb.2025.106879_bib14",
"volume": "16",
"year": "2025"
},
{
"article-title": "Vitamin d receptor rs2228570 and rs1544410 genetic polymorphisms frequency in Iraqi thalassemia patients compared to other ethnic populations",
"author": "Abbas",
"journal-title": "Gene Rep.",
"key": "10.1016/j.jsbmb.2025.106879_bib15",
"volume": "23",
"year": "2021"
},
{
"DOI": "10.1111/cen.14664",
"article-title": "Effects of vitamin d receptor gene polymorphisms on the prognosis of COVID-19",
"author": "Apaydin",
"doi-asserted-by": "crossref",
"first-page": "819",
"journal-title": "Clin. Endocrinol.",
"key": "10.1016/j.jsbmb.2025.106879_bib16",
"volume": "96",
"year": "2022"
},
{
"DOI": "10.3390/nu17182926",
"article-title": "Vitamin d genetics beyond serum 25 (OH) D: VDR rs2228570 (fokI) polymorphism, inflammation, and quality of life in orthopedic patients",
"author": "Larysz",
"doi-asserted-by": "crossref",
"first-page": "2926",
"journal-title": "Nutrients",
"key": "10.1016/j.jsbmb.2025.106879_bib17",
"volume": "17",
"year": "2025"
},
{
"DOI": "10.34172/aim.2022.73",
"article-title": "Quick COVID-19 severity index, CURB-65 and quick SOFA scores comparison in predicting mortality and risk factors of COVID-19 patients",
"author": "Kılınç Toker",
"doi-asserted-by": "crossref",
"first-page": "443",
"journal-title": "Arch. Iran. Med.",
"key": "10.1016/j.jsbmb.2025.106879_bib18",
"volume": "25",
"year": "2022"
},
{
"DOI": "10.1136/thorax.58.5.377",
"article-title": "Defining community acquired pneumonia severity on presentation to hospital: an international derivation and validation study",
"author": "Lim",
"doi-asserted-by": "crossref",
"first-page": "377",
"journal-title": "Thorax",
"key": "10.1016/j.jsbmb.2025.106879_bib19",
"volume": "58",
"year": "2003"
},
{
"DOI": "10.7861/clinmed.2022-news-concept",
"article-title": "The National early warning score: from concept to NHS implementation",
"author": "Williams",
"doi-asserted-by": "crossref",
"first-page": "499",
"journal-title": "Clin. Med",
"key": "10.1016/j.jsbmb.2025.106879_bib20",
"volume": "22",
"year": "2022"
},
{
"DOI": "10.1186/s13054-019-2459-9",
"article-title": "Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients",
"author": "Soo",
"doi-asserted-by": "crossref",
"first-page": "186",
"journal-title": "Crit. care (Lond. Engl. )",
"key": "10.1016/j.jsbmb.2025.106879_bib21",
"volume": "23",
"year": "2019"
},
{
"article-title": "Intensive care society state of the art (SOA) 2023 Congress abstracts",
"author": "Horner",
"first-page": "196",
"journal-title": "J. Intensive Care Soc.",
"key": "10.1016/j.jsbmb.2025.106879_bib22",
"volume": "24",
"year": "2023"
},
{
"DOI": "10.1007/BF01709751",
"article-title": "The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure. On behalf of the working group on Sepsis-Related problems of the european society of intensive care Medicine",
"author": "Vincent",
"doi-asserted-by": "crossref",
"first-page": "707",
"journal-title": "Intensive Care Med",
"key": "10.1016/j.jsbmb.2025.106879_bib23",
"volume": "22",
"year": "1996"
},
{
"DOI": "10.3758/BF03193146",
"article-title": "G* power 3: a flexible statistical power analysis program for the social, behavioral, and biomedical sciences",
"author": "Faul",
"doi-asserted-by": "crossref",
"first-page": "175",
"journal-title": "Behav. Res Methods",
"key": "10.1016/j.jsbmb.2025.106879_bib24",
"volume": "39",
"year": "2007"
},
{
"author": "Cohen",
"key": "10.1016/j.jsbmb.2025.106879_bib25",
"series-title": "Statistical power analysis for the behavioral sciences",
"year": "2013"
},
{
"DOI": "10.1016/S1474-4422(14)70120-6",
"article-title": "The glasgow coma scale at 40 years: standing the test of time",
"author": "Teasdale",
"doi-asserted-by": "crossref",
"first-page": "844",
"journal-title": "Lancet Neurol.",
"key": "10.1016/j.jsbmb.2025.106879_bib26",
"volume": "13",
"year": "2014"
},
{
"author": "Williams",
"key": "10.1016/j.jsbmb.2025.106879_bib27",
"series-title": "Royal college for physicians: national early warning score (NEWS): standardising the assessment of Acute-Illness severity in the NHS. 2012 London",
"year": "2012"
},
{
"DOI": "10.1155/ancp/6796922",
"article-title": "The association of VDR/fokI gene polymorphism and protein expression with histopathological alterations in patients with thyroid colloid nodule",
"author": "Abdalfatah",
"doi-asserted-by": "crossref",
"first-page": "6796922",
"journal-title": "Anal Cell Pathol (Amst)",
"key": "10.1016/j.jsbmb.2025.106879_bib28",
"volume": "2025",
"year": "2025"
},
{
"DOI": "10.1007/s40291-013-0060-5",
"article-title": "Rapid and simultaneous detection of vitamin d receptor gene polymorphisms by a single ARMS-PCR assay",
"author": "Jafari",
"doi-asserted-by": "crossref",
"first-page": "97",
"journal-title": "Mol. Diagn. Ther.",
"key": "10.1016/j.jsbmb.2025.106879_bib29",
"volume": "18",
"year": "2014"
},
{
"DOI": "10.1007/s40520-021-01831-0",
"article-title": "Severe vitamin d deficiency is not related to SARS-CoV-2 infection but May increase mortality risk in hospitalized adults: a retrospective case-control study in an arab gulf country",
"author": "Alguwaihes",
"doi-asserted-by": "crossref",
"first-page": "1415",
"journal-title": "Aging Clin. Exp. Res.",
"key": "10.1016/j.jsbmb.2025.106879_bib30",
"volume": "33",
"year": "2021"
},
{
"DOI": "10.3390/nu13072170",
"article-title": "Effects of a 2-Week 5000 IU versus 1000 IU vitamin D3 supplementation on recovery of symptoms in patients with mild to moderate Covid-19: a randomized clinical trial",
"author": "Sabico",
"doi-asserted-by": "crossref",
"journal-title": "Nutrients",
"key": "10.1016/j.jsbmb.2025.106879_bib31",
"volume": "13",
"year": "2021"
},
{
"DOI": "10.1186/s12967-021-02838-x",
"article-title": "Vitamin d status of arab gulf residents screened for SARS-CoV-2 and its association with COVID-19 infection: a multi-centre case-control study",
"author": "Al-Daghri",
"doi-asserted-by": "crossref",
"first-page": "166",
"journal-title": "J. Transl. Med",
"key": "10.1016/j.jsbmb.2025.106879_bib32",
"volume": "19",
"year": "2021"
},
{
"DOI": "10.1016/j.jsbmb.2010.03.020",
"article-title": "The genes encoding cytokines IL-2, IL-10 and IL-12B are primary 1alpha,25(OH)2D3 target genes",
"author": "Matilainen",
"doi-asserted-by": "crossref",
"first-page": "142",
"journal-title": "J. Steroid Biochem Mol. Biol.",
"key": "10.1016/j.jsbmb.2025.106879_bib33",
"volume": "121",
"year": "2010"
},
{
"DOI": "10.1111/1756-185X.14477",
"article-title": "Vitamin D-A prominent immunomodulator to prevent COVID-19 infection",
"author": "Ashique",
"doi-asserted-by": "crossref",
"first-page": "13",
"journal-title": "Int. J. Rheum. Dis.",
"key": "10.1016/j.jsbmb.2025.106879_bib34",
"volume": "26",
"year": "2023"
},
{
"DOI": "10.1007/s11154-021-09707-4",
"article-title": "Vitamin d regulation of immune function during covid-19",
"author": "Bikle",
"doi-asserted-by": "crossref",
"first-page": "279",
"journal-title": "Rev. Endocr. Metab. Disord.",
"key": "10.1016/j.jsbmb.2025.106879_bib35",
"volume": "23",
"year": "2022"
},
{
"DOI": "10.1016/j.chest.2021.10.031",
"article-title": "Pneumonia severity index and CURB-65 score are good predictors of mortality in hospitalized patients with SARS-CoV-2 Community-Acquired pneumonia",
"author": "Bradley",
"doi-asserted-by": "crossref",
"first-page": "927",
"journal-title": "Chest",
"key": "10.1016/j.jsbmb.2025.106879_bib36",
"volume": "161",
"year": "2022"
},
{
"author": "Score",
"key": "10.1016/j.jsbmb.2025.106879_bib37",
"series-title": "2: standardising the assessment of acute-illness severity in the NHS, updated report of a working party",
"year": "2017"
},
{
"DOI": "10.1016/j.jsbmb.2010.03.050",
"article-title": "Developmental vitamin D3 deficiency induces alterations in immune organ morphology and function in adult offspring",
"author": "Harvey",
"doi-asserted-by": "crossref",
"first-page": "239",
"journal-title": "J. Steroid Biochem Mol. Biol.",
"key": "10.1016/j.jsbmb.2025.106879_bib38",
"volume": "121",
"year": "2010"
},
{
"DOI": "10.1007/BF01709751",
"article-title": "The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure: on behalf of the working group on Sepsis-Related problems of the european society of intensive care Medicine (see contributors to the project in the appendix)",
"author": "Vincent",
"doi-asserted-by": "crossref",
"first-page": "707",
"journal-title": "Intensive Care Med",
"key": "10.1016/j.jsbmb.2025.106879_bib39",
"volume": "22",
"year": "1996"
},
{
"DOI": "10.1111/iji.12674",
"article-title": "Vitamin d receptor gene polymorphisms role in COVID-19 severity: results of a Mexican patients’ cohort",
"author": "Ochoa-Ramírez",
"doi-asserted-by": "crossref",
"first-page": "235",
"journal-title": "Int J. Immunogenet.",
"key": "10.1016/j.jsbmb.2025.106879_bib40",
"volume": "51",
"year": "2024"
},
{
"DOI": "10.1038/s41390-022-02275-6",
"article-title": "Vitamin d deficiency and vitamin d receptor fokI polymorphism as risk factors for COVID-19",
"author": "Zeidan",
"doi-asserted-by": "crossref",
"first-page": "1383",
"journal-title": "Pedia Res",
"key": "10.1016/j.jsbmb.2025.106879_bib41",
"volume": "93",
"year": "2023"
},
{
"DOI": "10.1016/j.cyto.2025.156958",
"article-title": "FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children",
"author": "Mohamed",
"doi-asserted-by": "crossref",
"journal-title": "Cytokine",
"key": "10.1016/j.jsbmb.2025.106879_bib42",
"volume": "191",
"year": "2025"
},
{
"DOI": "10.1016/j.jsbmb.2020.105588",
"article-title": "Unveiling molecular associations of polymorphic variants of VDR gene (fokI, bsmI and apaI) in multiple myeloma patients of Indian population",
"author": "Kumar",
"doi-asserted-by": "crossref",
"journal-title": "J. Steroid Biochem Mol. Biol.",
"key": "10.1016/j.jsbmb.2025.106879_bib43",
"volume": "199",
"year": "2020"
},
{
"DOI": "10.3390/jpm13121663",
"article-title": "Exploring the influence of VDR genetic variants taqI, apaI, and fokI on COVID-19 severity and long-COVID-19 symptoms",
"author": "Alhammadin",
"doi-asserted-by": "crossref",
"first-page": "1663",
"journal-title": "J. Pers. Med",
"key": "10.1016/j.jsbmb.2025.106879_bib44",
"volume": "13",
"year": "2023"
},
{
"DOI": "10.1093/aje/kwh101",
"article-title": "Limitations of the odds ratio in gauging the performance of a diagnostic, prognostic, or screening marker",
"author": "Pepe",
"doi-asserted-by": "crossref",
"first-page": "882",
"journal-title": "Am. J. Epidemiol.",
"key": "10.1016/j.jsbmb.2025.106879_bib45",
"volume": "159",
"year": "2004"
},
{
"DOI": "10.1136/bmj.h5527",
"article-title": "STARD 2015: an updated list of essential items for reporting diagnostic accuracy studies",
"author": "Bossuyt",
"doi-asserted-by": "crossref",
"first-page": "h5527",
"journal-title": "BMJ",
"key": "10.1016/j.jsbmb.2025.106879_bib46",
"volume": "351",
"year": "2015"
},
{
"DOI": "10.7554/eLife.89270.4",
"article-title": "Vitamin d constrains inflammation by modulating the expression of key genes on Chr17q12-21.1",
"author": "Kilic",
"doi-asserted-by": "crossref",
"journal-title": "Elife",
"key": "10.1016/j.jsbmb.2025.106879_bib47",
"volume": "12",
"year": "2024"
},
{
"DOI": "10.1038/ncpendmet0716",
"article-title": "Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity",
"author": "Adams",
"doi-asserted-by": "crossref",
"first-page": "80",
"journal-title": "Nat. Clin. Pr. Endocrinol. Metab.",
"key": "10.1016/j.jsbmb.2025.106879_bib48",
"volume": "4",
"year": "2008"
},
{
"article-title": "Diseases deriving from alterations of the ecological Niche—Part I: not regarding the holobiont",
"author": "Libertini",
"first-page": "57",
"key": "10.1016/j.jsbmb.2025.106879_bib49",
"series-title": "The Essential Revolution of Evolutionary Medicine: Interpreting Diseases and Population Aging",
"year": "2025"
},
{
"DOI": "10.1136/jclinpath-2012-201301",
"article-title": "Vitamin D: a negative acute phase reactant",
"author": "Waldron",
"doi-asserted-by": "crossref",
"first-page": "620",
"journal-title": "J. Clin. Pathol.",
"key": "10.1016/j.jsbmb.2025.106879_bib50",
"volume": "66",
"year": "2013"
},
{
"DOI": "10.1038/s41430-020-0558-y",
"article-title": "Vitamin d deficiency 2.0: an update on the current status worldwide",
"author": "Amrein",
"doi-asserted-by": "crossref",
"first-page": "1498",
"journal-title": "Eur. J. Clin. Nutr.",
"key": "10.1016/j.jsbmb.2025.106879_bib51",
"volume": "74",
"year": "2020"
},
{
"DOI": "10.1126/science.1123933",
"article-title": "Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response",
"author": "Liu",
"doi-asserted-by": "crossref",
"first-page": "1770",
"journal-title": "Science (New York N. Y. )",
"key": "10.1016/j.jsbmb.2025.106879_bib52",
"volume": "311",
"year": "2006"
},
{
"DOI": "10.1111/febs.15495",
"article-title": "Low plasma 25 (OH) vitamin d level is associated with increased risk of COVID-19 infection: an Israeli population-based study",
"author": "Merzon",
"doi-asserted-by": "crossref",
"first-page": "3693",
"journal-title": "FEBS J.",
"key": "10.1016/j.jsbmb.2025.106879_bib53",
"volume": "287",
"year": "2020"
},
{
"DOI": "10.1186/s40795-025-01060-y",
"article-title": "Effect of the vitamin d supplementation on clinical outcomes and inflammatory status in COVID-19 patients: an umbrella review",
"author": "Jafari-Vayghan",
"doi-asserted-by": "crossref",
"first-page": "86",
"journal-title": "BMC Nutr.",
"key": "10.1016/j.jsbmb.2025.106879_bib54",
"volume": "11",
"year": "2025"
},
{
"article-title": "The effect of vitamin d supplementation post COVID-19 infection and related outcomes: a systematic review and Meta-Analysis",
"author": "Sartini",
"journal-title": "Nutrients",
"key": "10.1016/j.jsbmb.2025.106879_bib55",
"year": "2024"
},
{
"article-title": "Vitamin d supplementation for managing COVID-19 in patients with vitamin d deficiency: a systematic review and meta-analysis of randomised controlled trials",
"author": "Zhu",
"journal-title": "BMJ Open",
"key": "10.1016/j.jsbmb.2025.106879_bib56",
"volume": "15",
"year": "2025"
},
{
"DOI": "10.1038/nrn3475",
"article-title": "Power failure: why small sample size undermines the reliability of neuroscience",
"author": "Button",
"doi-asserted-by": "crossref",
"first-page": "365",
"journal-title": "Nat. Rev. Neurosci.",
"key": "10.1016/j.jsbmb.2025.106879_bib57",
"volume": "14",
"year": "2013"
},
{
"DOI": "10.1016/S0140-6736(03)12516-0",
"article-title": "Genetic associations in large versus small studies: an empirical assessment",
"author": "Ioannidis",
"doi-asserted-by": "crossref",
"first-page": "567",
"journal-title": "Lancet",
"key": "10.1016/j.jsbmb.2025.106879_bib58",
"volume": "361",
"year": "2003"
},
{
"DOI": "10.1177/10888683241228328",
"article-title": "Power to detect what? Considerations for planning and evaluating sample size",
"author": "Giner-Sorolla",
"doi-asserted-by": "crossref",
"first-page": "276",
"journal-title": "Pers. Soc. Psychol. Rev.",
"key": "10.1016/j.jsbmb.2025.106879_bib59",
"volume": "28",
"year": "2024"
},
{
"DOI": "10.1016/S0140-6736(05)67531-9",
"article-title": "What makes a good genetic association study?",
"author": "Hattersley",
"doi-asserted-by": "crossref",
"first-page": "1315",
"journal-title": "Lancet",
"key": "10.1016/j.jsbmb.2025.106879_bib60",
"volume": "366",
"year": "2005"
},
{
"DOI": "10.1371/journal.pone.0059202",
"article-title": "The impact of study size on meta-analyses: examination of underpowered studies in cochrane reviews",
"author": "Turner",
"doi-asserted-by": "crossref",
"journal-title": "PloS One",
"key": "10.1016/j.jsbmb.2025.106879_bib61",
"volume": "8",
"year": "2013"
},
{
"DOI": "10.1111/joor.70002",
"article-title": "Research waste in temporomandibular disorders among registered randomised controlled trials: a Meta-Epidemiologic study",
"author": "Zhao",
"doi-asserted-by": "crossref",
"journal-title": "J. Oral. Rehabil.",
"key": "10.1016/j.jsbmb.2025.106879_bib62",
"year": "2025"
},
{
"DOI": "10.3945/ajcn.115.120873",
"article-title": "Vitamin d deficiency in Europe: pandemic?",
"author": "Cashman",
"doi-asserted-by": "crossref",
"first-page": "1033",
"journal-title": "Am. J. Clin. Nutr.",
"key": "10.1016/j.jsbmb.2025.106879_bib63",
"volume": "103",
"year": "2016"
},
{
"DOI": "10.1007/s11657-012-0093-0",
"article-title": "A global representation of vitamin d status in healthy populations",
"author": "Wahl",
"doi-asserted-by": "crossref",
"first-page": "155",
"journal-title": "Arch. Osteoporos.",
"key": "10.1016/j.jsbmb.2025.106879_bib64",
"volume": "7",
"year": "2012"
}
],
"reference-count": 64,
"references-count": 64,
"relation": {},
"resource": {
"primary": {
"URL": "https://linkinghub.elsevier.com/retrieve/pii/S0960076025002079"
}
},
"score": 1,
"short-title": [],
"source": "Crossref",
"special_numbering": "C",
"subject": [],
"subtitle": [],
"title": "Vitamin D pathway as a multi-level predictor of COVID-19 severity and mortality: Integrating serum levels, FokI (rs2228570) VDR polymorphism, and lung tissue expression",
"type": "journal-article",
"update-policy": "https://doi.org/10.1016/elsevier_cm_policy",
"volume": "255"
}
