Highlights from the 24th workshop on vitamin D in Austin, September 2022.

The 24th Workshop on Vitamin D was held September 7-9, 2022 in Austin, Texas and covered a wide diversity of research in the vitamin D field from across the globe. Here, we summarize the meeting, individual sessions, awards and presentations given.

Age and vitamin D affect the magnitude of the antibody response to the first dose of the SARS-CoV-2 BNT162b2 vaccine.

BACKGROUND: Most approved vaccines utilise a two-dose strategy. To enable larger groups of patients to receive the first dose, the UK government increased the gap between the two doses from three to twelve weeks. Here we report on the immunogenicity of the first dose, including effect of age and vitamin D status on these levels over an 8 week-period. METHODS: Blood samples were collected from healthcare workers (HCW) receiving their first BNT162b2 vaccine dose between January and February 2021. Antibody (Ab) production was measured, prior to and weekly for 4 weeks post immunization, and a final measurement was performed at 8 weeks. Serum vitamin D concentrations were also measured at baseline. FINDINGS: Immunization of 97 HCW induced an Ab response that peaked 3•2 weeks post immunization to decrease thereafter. Ab levels remained positive at 8 weeks. IgG peak concentration was negatively associated with age (ß=-0•440, p<0.001). Response to immunization was also significantly affected by vitamin D status (p=0•022), on average 29•3% greater peak value in individuals with 25(OH)D>50nmol/L. No other variable showed significant effect. INTERPRETATION: The first dose of BNT162b2 produced Ab levels that remained positive after 8 weeks. Peak was greater in younger subjects and 25(OH)D>50nmol/L was beneficial. Booster campaigns should take into consideration vitamin D status which is at its highest following a period of sunshine exposure or following oral supplementation (400-1000IU daily). FUNDING: 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.

Performance of the Abbott SARS-CoV-2 IgG II Quantitative Antibody Assay Including the New Variants of Concern, VOC 202012/V1 (United Kingdom) and VOC 202012/V2 (South Africa), and First Steps towards Global Harmonization of COVID-19 Antibody Methods.

In the initial stages of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) COVID-19 pandemic, a plethora of new serology tests were developed and introduced to the global market. Many were not evaluated rigorously, and there is a significant lack of concordance in results across methods. To enable meaningful clinical decisions to be made, robustly evaluated, quantitative serology methods are needed. These should be harmonized to a primary reference material, allowing for the comparison of trial data and improved clinical decision making. A comprehensive evaluation of the new Abbott IgG II anti-SARS-CoV-2 IgG method was undertaken using CLSI-based protocols. Two different candidate primary reference materials and verification panels were assessed with a goal to move toward harmonization. The Abbott IgG II method performed well across a wide range of parameters with excellent imprecision (<3.5%) and was linear throughout the positive range (tested to 38,365 AU/ml). The sensitivity (based on ≥14-day post-positive reverse transcription-PCR [RT-PCR] samples) and specificity were 98.3% (90.6% to 100.0%) and 99.5% (97.1% to 100%), respectively. The candidate reference materials showed poor correlation across methods, with mixed responses noted in methods that use the spike protein versus the nucleocapsid proteins as their binding antigen. The Abbott IgG II anti-SARS-CoV-2 measurement appears to be the first linear method potentially capable of monitoring the immune response to natural infection, including from new emerging variants. The candidate reference materials assessed did not generate uniform results across several methods, and further steps are needed to enable the harmonization process.

Performance of SARS-CoV-2 serology tests: Are they good enough?

In 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. SARS-CoV-2 patient samples (n = 43) were analyzed 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. EDI 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 was 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%. Serological 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.