Vitamin D blood levels and vitamin D receptor polymorphisms contribute to post-acute sequelae of severe acute respiratory syndrome coronavirus 2 severity in the pediatric patients

DOI record: { "DOI": "10.21203/rs.3.rs-7146347/v1", "URL": "http://dx.doi.org/10.21203/rs.3.rs-7146347/v1", "abstract": "<title>Abstract</title>\n <p><italic><bold>Background and Aims</bold></italic><italic>:</italic> Vitamin D, through the vitamin D receptor (VDR), modulates immune responses and may reduce inflammation linked to prolonged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) symptoms. While vitamin D deficiency is tied to severe Coronavirus disease 2019 (COVID-19) outcomes, its role in post-acute sequelae of SARS-CoV-2 (PASC) is unclear. This study examines the relationship between PASC severity in children and their vitamin D levels or VDR genetic variants.\n<italic><bold>Methods</bold></italic><italic>:</italic> Children with persistent and prolonged symptoms following SARS-CoV-2 infection were recruited from a hospital. A detailed questionnaire was administered, and blood samples were collected for comprehensive biomedical test. Deoxyribonucleic acid (DNA) from peripheral blood mononuclear cells (PBMCs) of the enrolled patients was extracted for genotyping of VDR genetic variants. The effects of vitamin D levels and VDR genetic variants on PASC severity were analyzed.\n<italic><bold>Results</bold></italic><italic>:</italic> A total of 123 patients were enrolled in the study, with 90 completing the PASC severity survey and 109 providing results from biomedical tests. Vitamin D levels showed a significant negative correlation with PASC scores (<italic>p</italic>=0.0052). There was a significant positive correlation (<italic>p</italic>&lt;0.05) between vitamin D levels and both lactate dehydrogenase (LDH) and aspartate amino transferase (AST), while neutrophils, lymphocytes, and eosinophils demonstrated a significant negative correlation (<italic>p</italic>&lt;0.05) with vitamin D levels. Patients with the GG genotype of the VDR genetic variant rs2228570 had lower PASC scores compared to those with the AA or AG genotypes. The highest PASC scores were observed in patients with 25-hydroxyvitamin D [25(OH)D] levels &lt; 20 ng/ml and the AA/AG genotype.\n<italic><bold>Conclusions</bold></italic><italic>:</italic> Both vitamin D levels and VDR genetic variants contribute to the severity of PASC in children, with a combined additive effect on the condition's severity.</p>", "accepted": { "date-parts": [ [ 2025, 7, 17 ] ] }, "author": [ { "affiliation": [ { "name": "Department of Microbiology & Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan." } ], "family": "Chen", "given": "Pei-Chi", "sequence": "first" }, { "affiliation": [ { "name": "Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan." } ], "family": "Hsu", "given": "Yu-Lung", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Public Health, China Medical University, Taichung, Taiwan." } ], "family": "Chen", "given": "Yen-Hsi", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Public Health, China Medical University, Taichung, Taiwan." } ], "family": "Lin", "given": "Chih-Yu", "sequence": "additional" }, { "affiliation": [ { "name": "Research Center of Allergy, Immunology and Microbiome (A.I.M.), China Medical University Hospital, China Medical University, Taichung 404327, Taiwan." } ], "family": "Hsieh", "given": "Miao-Hsi", "sequence": "additional" }, { "affiliation": [ { "name": "Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Taiwan." } ], "family": "Tsai", "given": "Hui-Ju", "sequence": "additional" }, { "affiliation": [ { "name": "Research Center of Allergy, Immunology and Microbiome (A.I.M.), China Medical University Hospital, China Medical University, Taichung 404327, Taiwan." } ], "family": "Kuo", "given": "Wen-Shuo", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Nursing, National Tainan Junior College of Nursing, Tainan, Taiwan." } ], "family": "Kao", "given": "Hui-Fang", "sequence": "additional" }, { "affiliation": [ { "name": "School of post-baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan." } ], "family": "Wang", "given": "Shulhn-Der", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Allergy & Immunology, China Medical University Children's Hospital, China Medical University, Taichung 404327, Taiwan" } ], "family": "Ho", "given": "Yu-Shan", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Allergy & Immunology, China Medical University Children's Hospital, China Medical University, Taichung 404327, Taiwan" } ], "family": "Cai", "given": "Cheng-Ye", "sequence": "additional" }, { "affiliation": [ { "name": "Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan." } ], "family": "Wu", "given": "Lawrence Shih-Hsin", "sequence": "additional" }, { "affiliation": [ { "name": "Department of Allergy and Immunology, China Medical University Children’s Hospital, China Medical University, Taichung 404327, Taiwan" } ], "family": "Wang", "given": "Jiu-Yao", "sequence": "additional" } ], "container-title": [], "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2025, 7, 23 ] ], "date-time": "2025-07-23T08:38:45Z", "timestamp": 1753259925000 }, "deposited": { "date-parts": [ [ 2025, 7, 23 ] ], "date-time": "2025-07-23T08:39:05Z", "timestamp": 1753259945000 }, "group-title": "In Review", "indexed": { "date-parts": [ [ 2025, 7, 23 ] ], "date-time": "2025-07-23T09:10:18Z", "timestamp": 1753261818280, "version": "3.41.2" }, "institution": [ { "name": "Research Square" } ], "is-referenced-by-count": 0, "issued": { "date-parts": [ [ 2025, 7, 23 ] ] }, "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "unspecified", "delay-in-days": 0, "start": { "date-parts": [ [ 2025, 7, 23 ] ], "date-time": "2025-07-23T00:00:00Z", "timestamp": 1753228800000 } } ], "link": [ { "URL": "https://www.researchsquare.com/article/rs-7146347/v1", "content-type": "text/html", "content-version": "vor", "intended-application": "text-mining" }, { "URL": "https://www.researchsquare.com/article/rs-7146347/v1.html", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "297", "original-title": [], "posted": { "date-parts": [ [ 2025, 7, 23 ] ] }, "prefix": "10.21203", "published": { "date-parts": [ [ 2025, 7, 23 ] ] }, "publisher": "Springer Science and Business Media LLC", "reference": [ { "DOI": "10.7554/eLife.86002", "article-title": "Pathogenic mechanisms of post-acute sequelae of SARS-CoV-2 infection (PASC)", "author": "Sherif ZA", "doi-asserted-by": "crossref", "first-page": "e86002", "journal-title": "Elife", "key": "ref1", "unstructured": "Sherif ZA, Gomez CR, Connors TJ, Henrich TJ, Reeves WB, RECOVER Mechanistic Pathway Task Force (2023) Pathogenic mechanisms of 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