Vitamin D

Reduced vitamin D levels associated with increased COVID-19 related deaths (2021)

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Type of publication:
Conference abstract

Author(s):
*Moudgil N.; *Oyegunle T.; *Makan A.; *Crawford E.; *Srinivasan K.S.; *Ahmad N.; *Dev D.; *Moudgil H

Citation:
American Journal of Respiratory and Critical Care Medicine; May 2021; vol. 203 (no. 9)

Abstract:
RATIONALE: Vitamin D supports immunity and inflammation by inhibiting proinflammatory cytokine release from macrophages and up-regulating the expression of anti-microbial peptides exhibiting anti-viral activity. Respiratory epithelial cells also convert inactive 25(OH)D (main circulating vitamin D) to 1,25(OH)2D3 enabling high local concentrations of this biologically active form to increase the expression of vitamin D-regulated genes. Studies continue to investigate the therapeutic effects and establish the optimal serum levels of 25(OH)D required to reduce the impact of respiratory tract infections whilst avoiding toxic hypercalcaemic high-dose 'blind' supplementation. Analysing patients admitted to hospital with COVID-19 (SARS-CoV-2 RNA) during the first phase of the pandemic, objectives and focus on reporting were to (1) document the population where measured vitamin D levels are readily available whilst quantifying those on supplements and (2) compare
outcome at discharge depending on most recent available vitamin D status. METHOD(S): Computer data including clinical outcomes were examined for the 516 patients (55% male) with mean age 67.4 (SD 18.3, range 0 to 100) years admitted from our semi-rural predominantly white European population to our District General Hospitals (Teaching) during the 4 months (March to June 2020) in the first phase of the COVID-19 illness in the UK. Outcomes (death during admission versus discharged alive) were analysed with SPSS comparing those with reduced versus adequate vitamin D levels. RESULT(S): Collectively (n=516), vitamin D levels (historical or updated) were available on 163 (31.5%) of patients; 17 (3.3%) undertaken during the admission. Data were skewed with median level 47 (interquartile range 24.1 to 66.9) nmol/L. 74 (14.3%) were already on vitamin D supplements and for an additional 10 (1.9%) this was initiated during the admission. Among the 163 patients, 86 (52.7%) had reduced vitamin D levels (deficient or insufficient) and these had worse outcomes with 29/86 (33.7%) having died during the admission compared with 13/74 (17.6%) of those with adequate levels: X2 (df 1, n=163) 6.02, p=.014. Table 1 categorises
distribution of values. CONCLUSION(S): Data highlight (1) less than a third of admitted COVID-19 patients have recorded vitamin D levels and of these more than half have reduced levels, (2) 14.3% are already taking vitamin D, (3) very few get
tested during the acute admission or get started on supplements, and (4) there is a statistical difference highlighting adverse outcome (death versus discharged alive) for those with reduced vitamin D levels.

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Design and implementation of a custom next generation sequencing panel for selected vitamin D associated genes (2017)

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Type of publication:
Journal article

Author(s):
Benson K.A.; Maxwell A.P.; Smyth L.J.; Kilner J.; McKnight A.J.; *Chand S. ; Borrows R.

Citation:
BMC Research Notes; Jul 2017; vol. 10 (no. 1); p. 348

Abstract:
 BACKGROUND: Biologically active vitamin D has an important regulatory role within the genome. It binds the vitamin D receptor (VDR) in order to control the expression of a wide range of genes as well as interacting with the epigenome to modify chromatin and methylation status. Vitamin D deficiency is associated with several human diseases including end-stage renal disease.METHODS: This article describes the design and testing of a custom, targeted next generation sequencing (NGS) panel for selected vitamin D associated genes. Sequencing runs were used to determine the effectiveness of the panel for variant calling, to compare efficiency and data across different sequencers, and to perform representative, proof of principle association analyses. These analyses were underpowered for significance testing. Amplicons were designed in two pools (163 and 166 fragments respectively) and used to sequence two cohorts of renal transplant recipients on the Ion Personal Genome Machine (PGM)TM and Ion S5TM XL desktop sequencers.RESULTS: Coverage was provided for 43.8 kilobases across seven vitamin D associated genes (CYP24A1, CUBN, VDR, GC, NADSYN1, CYP27B1, CYP2R1) as well as 38 prioritised SNPs. Sequencing runs provided sufficient sequencing quality, data output and validated the effective library preparation and panel design.CONCLUSIONS: This novel, custom-designed, validated panel provides a fast, cost effective, and specific approach for the analysis of vitamin D associated genes in a wide range of patient cohorts. This article does not report results from a controlled health-care intervention.

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