Prospective Evaluation of the ESPGHAN Guidelines for Diagnosis of Celiac Disease in New Zealand Children.

OBJECTIVE: The 2012 European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) guideline for diagnosis of celiac disease (CD) questioned the requirement for intestinal biopsy to confirm the diagnosis. The guideline recommends that in symptomatic patients with consistent human leukocyte antigen (HLA) subtypes, the diagnostic accuracy of strongly positive serology is sufficient to confirm the diagnosis. We prospectively assessed these guidelines in a "real-life" clinical setting. METHODS: One hundred and four children referred for evaluation of possible CD were prospectively recruited. Following informed consent, blood was drawn for serological testing and HLA analysis at upper gastrointestinal endoscopy. Histological findings according to Marsh criteria were correlated with blood results and the accuracy of the guideline analyzed.The study also examined the role of deamidated gliadin peptide (DGP) in the diagnosis of CD. RESULTS: For symptomatic patients with consistent HLA subtypes, strongly positive serology (as described in the ESPGHAN guidelines) accurately predicted biopsy-proven CD in >95% of cases. DGP was positive in fewer patients than anti-TG2 or EMA. Incorporation of DGP as a second confirmatory serological test in place of EMA was associated with maintained predictive value of guideline, but fewer patients fulfilling criteria for biopsy-free diagnosis. CONCLUSIONS: The ESPGHAN guideline performs well in our population. Adoption of the guideline would reduce the number of patients requiring endoscopy without compromise in diagnostic accuracy. The involvement of pediatric gastroenterological expertise, however, remains key to diagnosis of CD.

SARS-CoV-2 antibodies in the Southern Region of New Zealand, 2020.

During New Zealand's first outbreak in early 2020 the Southern Region had the highest per capita SARS-CoV-2 infection rate. Polymerase chain reaction (PCR) testing was initially limited by a narrow case definition and limited laboratory capacity, and cases may have been missed. Our objectives were to evaluate the Abbott SARS-CoV-2 IgG nucleocapsid assay, alongside spike-based assays, and to determine the frequency of antibodies among PCR-confirmed and probable cases, and higher risk individuals in the Southern Region of New Zealand. Pre-pandemic sera (n=300) were used to establish assay specificity and sera from PCR-confirmed SARS-CoV-2 patients (n=78) to establish sensitivity. For prevalence analysis, all samples (n=1214) were tested on the Abbott assay, and all PCR-confirmed cases (n=78), probable cases (n=9), and higher risk individuals with 'grey-zone' (n=14) or positive results (n=11) were tested on four additional SARS-CoV-2 serological assays. The median time from infection onset to serum collection for PCR-confirmed cases was 14 weeks (range 11-17 weeks). The Abbott assay demonstrated a specificity of 99.7% (95% CI 98.2-99.99%) and a sensitivity of 76.9% (95% CI 66.0-85.7%). Spike-based assays demonstrated superior sensitivity ranging 89.7-94.9%. Nine previously undiagnosed sero-positive individuals were identified, and all had epidemiological risk factors. Spike-based assays demonstrated higher sensitivity than the Abbott IgG assay, likely due to temporal differences in antibody persistence. No unexpected SARS-CoV-2 infections were found in the Southern Region of New Zealand, supporting the elimination status of the country at the time this study was conducted.

Comprehensive analysis of SARS-CoV-2 antibody dynamics in New Zealand.

OBJECTIVES: Circulating antibodies are important markers of previous infection and immunity. Questions remain with respect to the durability and functionality of SARS-CoV-2 antibodies. This study explored antibody responses in recovered COVID-19 patients in a setting where the probability of re-exposure is effectively nil, owing to New Zealand's successful elimination strategy. METHODS: A triplex bead-based assay that detects antibody isotype (IgG, IgM and IgA) and subclass (IgG1, IgG2, IgG3 and IgG4) responses against Nucleocapsid (N) protein, the receptor binding domain (RBD) and Spike (S) protein of SARS-CoV-2 was developed. After establishing baseline levels with pre-pandemic control sera (n = 113), samples from PCR-confirmed COVID-19 patients with mild-moderate disease (n = 189) collected up to 8 months post-infection were examined. The relationship between antigen-specific antibodies and neutralising antibodies (NAbs) was explored with a surrogate neutralisation assay that quantifies inhibition of the RBD/hACE-2 interaction. RESULTS: While most individuals had broad isotype and subclass responses to each antigen shortly after infection, only RBD and S protein IgG, as well as NAbs, were relatively stable over the study period, with 99%, 96% and 90% of samples, respectively, having responses over baseline 4-8 months post-infection. Anti-RBD antibodies were strongly correlated with NAbs at all time points (Pearson's r ≥ 0.87), and feasibility of using finger prick sampling to accurately measure anti-RBD IgG was demonstrated. CONCLUSION: Antibodies to SARS-CoV-2 persist for up to 8 months following mild-to-moderate infection. This robust response can be attributed to the initial exposure without immune boosting given the lack of community transmission in our setting.