Investigation of the Relationship between Vitamin D Deficiency and Vitamin D-Binding Protein Polymorphisms in Severe COVID-19 Patients

This study explores the association of vitamin D-binding protein (VDBP) gene polymorphisms, vitamin D levels, and the severity of COVID-19, including the need for intensive care unit (ICU) hospitalization. We analyzed a cohort of 56 consecutive age- and gender-matched adult COVID-19-positive patients and categorized them into three groups: outpatients with mild illness, inpatients with moderate disease, and ICU patients. We measured levels of free, total, and bioavailable 25-hydroxyvitamin D [25(OH)D], VDBP, and albumin. VDBP polymorphisms <i>rs5488</i> and <i>rs7041</i> were identified using real-time PCR. A significant proportion of ICU patients were vitamin D-deficient (56.25%) compared to outpatients (10%) and inpatients (5%) (<i>p</i> = 0.0003). ICU patients also had notably lower levels of VDBP (median: 222 mg/L) and total 25(OH)D (median: 18.8 ng/mL). Most patients carried heterozygous <i>rs7041</i> (60.7%) and wild-type <i>rs4588</i> (58.9%) genotypes. The distribution of <i>rs7041</i> SNP varied significantly among groups (<i>p</i> = 0.0301), while <i>rs4588</i> SNP distribution did not (<i>p</i> = 0.424). Heterozygous <i>rs4588</i> patients had significantly lower VDBP levels (<i>p</i> = 0.029) and reduced bioavailable 25(OH)D compared to those with wild-type <i>rs4588</i> (<i>p</i> = 0.020). Our findings indicate that VDBP gene polymorphisms, particularly <i>rs7041</i> and rs4588, are associated with vitamin D status and the severity of COVID-19. The lower VDBP levels and bioavailable vitamin D in ICU patients suggest that these genetic variants may influence disease severity and hospitalization needs. These results highlight the potential role of VDBP polymorphisms in COVID-19 severity, suggesting that genetic screening could be valuable in assessing the risk of severe outcomes and guiding personalized treatment strategies.