ABSTRACT
Background: Randomised controlled trials (RCT) to determine the influence of vitamin D on bone mineral content (BMC) and fracture risk in children of Black African ancestry are lacking.Methods: We conducted a sub-study nested within a Phase 3 RCT of weekly oral supplementation with 10,000 IU vitamin D3 in HIV-uninfected Cape Town schoolchildren of Black African ancestry aged 6-11 years. Outcomes were BMC at the whole body less head (WBLH) and lumbar spine (LS) and serum concentrations of 25-hydroxyvitamin D3 (25[OH]D3), parathyroid hormone (PTH) and bone turnover markers. Incidence of fractures was an outcome of the main trial.Findings: 1682 children were enrolled in the main trial, of whom 450 also participated in the sub-study. Among sub-study participants, end-trial serum 25(OH)D3 concentrations were higher for participants allocated to vitamin D vs. placebo (adjusted mean difference [aMD] 39.9 nmol/L, 95% CI 36.1 to 43.6, P<0.001) and serum PTH concentrations were lower (aMD -0.55 pmol/L, 95% CI -0.94 to -0.17, P=0.005). However, no interarm differences were seen for WBLH BMC (aMD -8.0 g, 95% CI -30.7 to 14.7) or LS BMC (aMD -0.3 g, 95% CI -1.3 to 0.8), or for serum concentrations of bone turnover markers (P≥0.28). In the main trial, allocation did not influence fracture risk (adjusted odds ratio 0.70, 95% CI 0.27 to 1.85, P=0.48).Interpretation: Weekly vitamin D supplementation elevated serum 25(OH)D3 concentrations and suppressed serum PTH concentrations in HIV-uninfected South African schoolchildren of Black African ancestry but did not influence BMC, bone turnover markers or fracture risk.FUNDING: Medical Research CouncilTrial Registration: Registered on the South African National Clinical Trials Register (DOH-27-0916-5527) and ClinicalTrials.gov (ref NCT02880982).Funding: This research was funded by the UK Medical Research Council (refs MR/R023050/1 and MR/M026639/1, both awarded to ARM). RJW was supported by Wellcome (104803, 203135). He also received support from the Francis Crick Institute which is funded by Cancer Research UK (FC2112), the UK Medical Research Council (FC2112) and Wellcome (FC2112). Declaration of Interest: ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests.Ethical Approval: The trial was sponsored by Queen Mary University of London, approved by the University of Cape Town Faculty of Health Sciences Human Research Ethics Committee (Ref: 796/2015) and the London School of Hygiene and Tropical Medicine Observational/Interventions Research Ethics Committee (Ref: 7450-2).
Subject(s)
HIV Infections , Bone Diseases, Metabolic , Musculoskeletal Diseases , Parathyroid Diseases , COVID-19 , Fractures, BoneABSTRACT
Background: Controlling the spread of the COVID-19 pandemic relies heavily on worldwide immunization programs. Most of the current approved vaccines utilise a two-dose strategy to prime-boost the immune system. To enable larger groups of patients to receive the first dose, the UK government increased the gap between the two doses from three to 12 weeks. Here we report on the immunogenicity of the first dose.Methods: Anti SARS-CoV-2 IgG production (quantitative Abbott immunoassays) and vitamin D (25-hydroxyvitamin D (25(OH)D; LCMS) and 1-α,25-dihydroxyvitamin D (1,25(OH) 2 D, LCMS)) were measured in a group of 105 HCW, post immunization with the Pfizer/BioNTech vaccine.Findings: The anti-Spike IgG Ab response showed minimal change within the first week, rapidly peaked 3·2 weeks post immunization, subsequently decreasing to the nadir at 8 weeks prior to the scheduled second dose being administered. All subjects who responded with positive anti-Spike IgG Abs, retained significant levels at 8 weeks. Response to immunization was significantly modified by age and replete vitamin D status (25(OH)D>50 nmol/L).Interpretation: The results indicate that in this cohort 1) Ab levels are greatest 3-4 weeks post the first dose of the Pfizer/BioNTech vaccine 2) Abs are still circulating eight weeks post first dose 3) age significantly modifies the initial Ab response, the youngest decile having a greater peak and faster decline, resulting in 4) no significant difference in Ab concentration with age at W8 and 5) baseline vitamin D affected the peak of response, with vitamin D replete individuals showing the strongest Ab response.Funding Information: Abbott Diagnostics Ltd supplied the kits used to quantify the anti-SARS -CoV-2 Spike IgG and technical support as well as provided financial support for sample collections.Declaration of Interests: Abbott Diagnostics Ltd provided the necessary immunoassay for analysis of the samples for SARS-CoV-2 IgG and financial support for collection of samples. SR and MB work at Abbott Diagnostics Ltd. All other authors have no conflict of interest. Ethics Approval Statement: All participants provided written informed consent. The study was approved by the Health Research Authority Health and Care Research Wales ethical committee (IRAS#292799).
Subject(s)
COVID-19ABSTRACT
BackgroundIn the emergency of the SARS-CoV-2 pandemic, great efforts were made to quickly provide serology testing to the medical community however, these methods have been introduced into clinical practice without the complete validation usually required by the regulatory organizations. MethodsSARS-CoV-2 patient samples (n=43) were analysed alongside pre-pandemic control specimen (n=50), confirmed respiratory infections (n=50), inflammatory polyarthritis (n=22) and positive for thyroid stimulating immunoglobulin (n=30). Imprecision, diagnostic sensitivity and specificity and concordance were evaluated on IgG serologic assays from EuroImmun, Epitope Diagnostics (EDI), Abbott Diagnostics and DiaSorin and a rapid IgG/IgM test from Healgen. ResultsEDI and EuroImmun imprecision was 0.02-14.0% CV. Abbott and DiaSorin imprecision (CV) ranged from 5.2% - 8.1% and 8.2% - 9.6% respectively. Diagnostic sensitivity of the assays were 100% (CI: 80-100%) for Abbott, EDI and EuroImmun and 95% (CI: 73-100%) for DiaSorin at [≥]14 days post PCR. Only the Abbott assay had a diagnostic specificity of 100% (CI: 91-100%). EuroImmun cross-reacted in 3 non-SARS-CoV-2 respiratory infections and 2 controls. The DiaSorin displayed more false negative results and cross-reacted in six cases across all conditions tested. EDI had one cross-reactive sample. The Healgen rapid test showed excellent sensitivity and specificity. Overall, concordance of the assays ranged from 76.1% to 97.9%. ConclusionsSerological tests for SARS-CoV-2 showed good analytical performance. The head-to-head analysis of samples revealed differences in results that may be linked to the use of nucleocapsid or spike proteins. The point of care device tested demonstrated adequate performance for antibody detection.