Previous SARS-CoV-2 Infection Is Not Associated With Increased Celiac Disease Autoimmunity in Children and Adolescents.

INTRODUCTION: Recent reports suggest severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections may increase the risk of celiac disease autoimmunity. This study aims to evaluate potential associations between coronavirus disease 2019 infection and tissue transglutaminase autoantibodies (TGA) immunoglobulin A. METHODS: From 2020 to 2021, cross-sectional screening for SARS-CoV-2 antibodies and TGA was offered to 4,717 children in Colorado through the Autoimmunity Screening for Kids study. Multivariable logistic regression assessed association between previous SARS-CoV-2 infection and TGA positivity. RESULTS: Previous SARS-CoV-2 infection was not associated with TGA positivity (odds ratio 1.02, 95% confidence interval 0.63-1.59; P = 0.95). DISCUSSION: In this large-scale analysis, previous SARS-CoV-2 infection was not associated with celiac disease autoimmunity in Colorado children.

Similar Time Course of Humoral Response to SARS-CoV-2 mRNA Vaccines in People With and Without Type 1 Diabetes.

Objective: To assess whether the immunogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines or breakthrough infection rates differ between patients with type 1 diabetes (T1D) and control subjects. Research Design and Methods: A prospective 12-month follow-up of 27 adults with T1D and 89 control subjects who received at least two doses of either the mRNA-1273 or BNT162b2 vaccine. Primary outcomes: total antibodies against the receptor-binding domain and neutralizing antibodies. A multivariate repeated measures model evaluated potential determinants of antibody response. Results: Neither antibody levels nor breakthrough infection rates after vaccination differed in T1D and non-T1D groups. Older age predicted lower antibody levels, whereas SARS-CoV-2 infection or booster vaccine resulted in higher antibody levels in both groups. mRNA-1273 was associated with higher antibody levels than BNT162b2 until 6 months after the first dose. Conclusions: Persons with and without T1D have similar humoral antibody responses to SARS-CoV-2 mRNA vaccines during 12-months of follow-up.

SARS-CoV-2 Infections and Presymptomatic Type 1 Diabetes Autoimmunity in Children and Adolescents From Colorado, USA, and Bavaria, Germany.

This study screens more than 50 000 youths in diverse populations of Colorado and Bavaria to assess whether previous SARS-CoV-2 infection was associated with autoimmunity, which predicts future type 1 diabetes.

A High-throughput Multiplexed Screening for Type 1 Diabetes, Celiac Diseases, and COVID-19.

An ongoing clinical trial, Autoimmunity Screening for Kids (ASK), is the first screening study in the general population for type 1 diabetes (T1D) and celiac disease in the United States. With the coronavirus disease 2019 (COVID-19) pandemic, the epidemiology of COVID-19 in the general population and knowledge about the association between COVID-19 infection and T1D development are urgently needed. The currently standard screening method of the radio-binding assay (RBA) has met two great challenges: low efficiency with a single assay format and low disease specificity with a large proportion of low-affinity antibodies generated in screening. With the platform of the multiplex electrochemiluminescence (ECL) assay we established previously, a novel 6-Plex ECL assay was developed that combines, in a single well, all four islet autoantibodies (IAbs) to insulin, glutamic acid decarboxylase (GAD65), insulinoma antigen 2 (IA-2), and Zinc transporter 8 (ZnT8) for T1D, transglutaminase autoantibodies (TGA) for celiac disease, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) antibodies for COVID-19. The assay was validated in blind using 880 samples from the ASK study, including 325 positive samples and 555 all antibody-negative samples, and compared with the standard RBAs and a single ECL assay. With the advantages of high efficiency, low cost, and low serum volume, this assay has been accepted as the primary screening tool for the ASK study.

SARS-CoV-2 Infection Is Not Associated with Presence of Islet Autoantibodies in Children: Autoimmunity Screening for Kids (ASK)

Viral infections may trigger islet autoimmunity leading to type 1 diabetes (T1D) . We hypothesized SARS-CoV-2 infection is associated with presence of islet autoantibodies (IAb) in children. Between 8/2020 and 12/2021, ASK screened 47general population Colorado children aged 1-17 y for IAb to GAD, insulin, IA-2 and ZnT8 as well as antibodies to SARS-CoV-2 receptor binding domain (CoV-2 RBDAb) - a sensitive and specific marker of infection. Of those, 4172 (89%) have not previously received SARS-CoV-2 vaccine. During the study period, prevalence of CoV-2 RBDAb increased in unvaccinated from 1% to 58% and up to 100% among vaccinated. Among all children, the prevalence increased from 1% to 72% - an estimate of herd immunity (Figure) . Among the unvaccinated, prevalence of multiple or single high-affinity IAb did not differ between children positive vs. negative for CoV-2 RBDAb, respectively 1.23% (16/1297) vs. 1.00% (29/2875) , p=0.52. In multivariate logistic regression, presence of IAb was not associated with presence of CoV-2 RBDAb (OR=1.40, p=0.31) , adjusting for age, sex, race/ethnicity, and family history of T1D. While we found no association between past SARS-CoV-2 infection and islet autoimmunity, a confirmation in a larger population is warranted. Longer follow-up will help assess whether SARS-CoV2 infection accelerates progression from islet autoimmunity to diabetes.

High-Throughput Multiplex Electrochemiluminescence Assay Applicable to General Population Screening for Type 1 Diabetes and Celiac Disease.

Objective: Large-scale screening of the general population for islet autoantibodies (IAbs) to detect type 1 diabetes (T1D) has started worldwide. The standard screening method of separate radio-binding assay (RBA) for each IAb is an inefficient bottleneck. Furthermore, most positive results by RBA in screening of general population individuals without a clinical diagnosis of T1D are low-affinity and not predictive of future diabetes. Research Design and Methods: We have developed and validated a novel 6-Plex assay based on electrochemiluminescence (ECL) technology that combines in a single well high-affinity IAbs (to insulin, GAD, IA-2, and ZnT8), transglutaminase autoantibodies for celiac disease, and severe acute respiratory syndrome coronavirus 2 antibodies. The Autoimmunity Screening for Kids (ASK) provided 880 serum samples, from 828 children aged 1-17 years without diabetes who were previously tested for IAbs using single ECL assays and RBA assays. Results: Levels of all six antibodies in the 6-Plex ECL assay correlated well with respective single ECL assay levels. Similar to single ECL assays, the 6-Plex ECL assay positivity was congruent with the RBA in 95% (35/37) of children who later developed T1D and in 88% (105/119) high-risk children with multiple IAbs. In contrast, only 56% (86/154, P < 0.0001) of children with persistent single IAb by RBA were found to be positive by 6-Plex ECL assay. Of 555 samples negative for all IAbs by RBA, few (0.2%-0.5%) were positive at low levels in the 6-Plex ECL assay. Conclusions: The study demonstrated that the 6-Plex ECL assay compares favorably to the standard RBAs in terms of disease specificity for general population screening in children. The 6-Plex ECL assay was therefore adopted as the primary screening tool in the general population screening ASK program with advantages of high efficiency, low cost, and low serum volume.

Prevalence of SARS-CoV-2 Antibodies in Children and Adults with Type 1 Diabetes.

Objective: As diabetes is a risk factor for severe symptoms, hospitalization, and death with COVID-19 disease, we aimed to assess the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in children and adults with and without type 1 diabetes in Colorado during 2020. Research Design and Methods: We developed a highly sensitive and specific test for antibodies against SARS-CoV-2 and measured the antibodies in children and adults with new-onset (n = 129) and established type 1 diabetes (n = 94) seen for routine diabetes care at our center between January and October 2020. The antibodies were also measured in 562 children and 102 adults from the general population of Colorado. Results: The prevalence of SARS-CoV-2 antibodies in persons with new-onset type 1 diabetes (0.8%; 95% confidence interval 0.1%-4.2%) or those with established disease (4.3%; 1.7%-10.4%) did not differ from that in the general population children (2.8%; 1.8%-4.6%) or adults (3.9%; 1.5%-9.7%). In a subset of individuals with positive antibodies (n = 31), antibodies remained positive for up to 9 months, although the levels decreased starting 3 months after the infection (P = 0.007). Conclusions: From January to October 2020, the prevalence of SARS-CoV-2 antibodies were not different in children and adults with and without type 1 diabetes in Colorado. We found no evidence for increased prevalence of COVID-19 infections among youth with newly diagnosed type 1 diabetes. (COMIRB Protocol 20-1007).