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1.
J Vis Exp ; (185)2022 07 05.
Article in English | MEDLINE | ID: covidwho-1954156

ABSTRACT

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.


Subject(s)
COVID-19 , Celiac Disease , Diabetes Mellitus, Type 1 , Autoantibodies , COVID-19/diagnosis , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/epidemiology , Glutamate Decarboxylase , Humans , SARS-CoV-2 , Sensitivity and Specificity
2.
Arch Dis Child ; 107(8): 747-751, 2022 08.
Article in English | MEDLINE | ID: covidwho-1950042

ABSTRACT

OBJECTIVE: European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) guidelines on coeliac disease (CD) recommend that children who have IgA-based antitissue transglutaminase (TGA-IgA) titre ≥10× upper limit of normal (ULN) and positive antiendomysial antibody, can be reliably diagnosed with CD via the no-biopsy pathway. The aim of this study was to examine the relationship between TGA-IgA ≥5×ULN and histologically confirmed diagnosis of CD. METHODS: Data including TGA-IgA levels at upper gastrointestinal endoscopy and histological findings from children diagnosed with CD following endoscopy from 2006 to 2021 were analysed. CD was confirmed by Marsh-Oberhuber histological grading 2 to 3 c. Statistical analysis was performed using χ² analysis (p<0.05= significant). RESULTS: 722 of 758 children had histological confirmation of CD. 457 children had TGA-IgA ≥5×ULN and 455 (99.5%) of these had histological confirmation for CD; the two that did not had eventual diagnosis of CD based on clinicopathological features. 114 of 457 had between TGA-IgA ≥5×ULN and <10×ULN, all had confirmed CD. The likelihood of a positive biopsy with TGA-IgA ≥5×ULN (455/457) compared with TGA-IgA <5×ULN (267/301) has strong statistical significance (p<0.00001). The optimal TGA-IgA cut-off from receiver operating characteristic curve analysis was determined to be below 5×ULN for the two assays used. CONCLUSION: 99.5% of children with TGA-IgA ≥5×ULN had histological confirmation of CD, suggesting that CD diagnosis can be made securely in children with TGA-IgA ≥5×ULN. If other studies confirm this finding, there is a case to be made to modify the ESPGHAN guidelines to a lower threshold of TGA-IgA for serological diagnosis of CD.


Subject(s)
Celiac Disease , Transglutaminases , Autoantibodies , Biopsy , Celiac Disease/diagnosis , Child , Humans , Immunoglobulin A , Transglutaminases/blood
3.
Diabetes Technol Ther ; 24(7): 502-509, 2022 07.
Article in English | MEDLINE | ID: covidwho-1864939

ABSTRACT

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.


Subject(s)
COVID-19 , Celiac Disease , Diabetes Mellitus, Type 1 , Autoantibodies , Celiac Disease/diagnosis , Child , Humans , Sensitivity and Specificity
4.
Arch Dis Child ; 107(6): 536-537, 2022 06.
Article in English | MEDLINE | ID: covidwho-1861594
6.
Ann Med ; 54(1): 617-621, 2022 12.
Article in English | MEDLINE | ID: covidwho-1692413

ABSTRACT

BACKGROUND: The coronavirus disease 2019 (COVID-19), an acute respiratory disease caused by a novel coronavirus (SARS-CoV-2), is emerging as a worldwide public health emergency. Several scientific contributions reported the potential relevance of human leukocyte antigen (HLA) polymorphism and susceptibility to viruses, such as SARS-CoV. In our study, we examined a population of coeliac subjects presenting the HLA haplotype DQ2 and/or DQ8. Our aim was to evaluate whether HLA DQ2 and/or DQ8 haplotype play a role in SARS-CoV-2-infection. The aim was also to evaluate the difficulty in following the gluten-free diet due to all the adversities produced by the pandemic, such as the food supply disruption, and the difficulties in managing the clinical follow-up. METHODS: 191 consecutive coeliac patients completed a questionnaire on their current clinical status, psychological effects, and management of the gluten-free diet experienced during the COVID-19 pandemic and questions regarding possible SARS-CoV-2 infection. RESULTS: Out of the 191 patients who participated in the study, 42 were full-blown coeliac and 149 were in remission. From the answers provided, 84.8% of patients declared that they no longer consider themselves vulnerable to COVID-19 as they suffer from coeliac disease; 94.2% of patients did not encounter any difficulties in managing the gluten-free diet or in acquiring specific foods and 64.9% of patients in our study underwent diagnostic testing for SARS-CoV-2. Out of this number, 31.5% did so due to contacts with subjects affected by COVID-19, 26.6% for work related reasons, 11.3% due to flu-like symptoms and 30.6% for other reasons. Only 5.8% of the enrolled patients received a diagnosis of COVID-19. Out of all the patients in our population who were diagnosed with COVID-19, 94.8% developed no symptoms and none of them needed hospitalization or intensive care. CONCLUSION: The hypothesis that the HLADQ2 and/or DQ8 haplotype plays a protective role against SARS-CoV-2 infection, as against other viral infections, is intriguingly suggestive.KEY MESSAGESCOVID-19 as a public health emergency;SARS-CoV-2 and possible complications in coeliac disease;Role of HLA DQ2 and/or DQ8 in SARS-CoV-2 infection.


Subject(s)
COVID-19 , Celiac Disease , HLA-DQ Antigens/genetics , COVID-19/complications , COVID-19/genetics , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Celiac Disease/genetics , Critical Care , Haplotypes , Humans , Pandemics , SARS-CoV-2
7.
BMJ Paediatr Open ; 5(1): e001152, 2021.
Article in English | MEDLINE | ID: covidwho-1476631

ABSTRACT

Introduction: Coeliac disease (CD) occurs in 1% of the population, develops early in life and is severely underdiagnosed. Undiagnosed and untreated disease is associated with short-term and long-term complications. The current healthcare approach is unable to solve the underdiagnosis of CD and timely diagnosis and treatment is only achieved by active case finding. Aim: to perform a case finding project to detect CD children who visit the Youth Health Care Centres (YHCCs) in a well-described region in the Netherlands to evaluate whether it is feasible, cost-effective and well accepted by the population. Methods/analysis: Prospective intervention cohort study. Parents of all children aged 12 months and 4 years attending the YHCCs for a regular visit are asked whether their child has one or more CD-related symptoms from a standardised list. If so, they will be invited to participate in the case finding study. After informed consent, a point of care test (POCT) to assess CD-specific antibodies against tissue transglutaminase (TG2A) is performed onsite the YHCCs. If the POCT is positive, CD is highly suspected and the child will be referred to hospital for definitive diagnosis according to the Guideline Coeliac Disease of the European Society for Pediatric Gastroenterology, Hepatology and Nutrition guideline. Main outcomes: Incidence rate of new CD diagnoses in the study region in comparison to the one in the same age diagnosed by standard of care in the rest of the Netherlands.Feasibility and cost-effectiveness of active CD case finding at the YHCCs. All costs of active case finding, diagnostics and treatment of CD and the potential short-term and long-term consequences of the disease will be calculated for the setting with and without case finding.Ethical acceptability: by questionnaires on parental and healthcare professionals' satisfaction.A statistical analysis plan was prepared and is published on the GLUTENSCREEN website (Statistical-Analysis-Plan-11-5-2021_def.pdf (glutenscreen.nl) and added as annex 1). Ethics and dissemination: The Medical Ethics Committee Leiden approved this study. If we prove that case finding at the YHCC is feasible, cost-effective and well accepted by the population, implementation is recommended. Trial registration number: NL63291.058.17.


Subject(s)
Celiac Disease , Adolescent , Celiac Disease/diagnosis , Child , Cohort Studies , Delivery of Health Care , Early Diagnosis , Humans , Infant , Netherlands/epidemiology , Prospective Studies
8.
Eur J Gastroenterol Hepatol ; 33(11): 1460-1461, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1450469
9.
Curr Opin Gastroenterol ; 37(6): 619-624, 2021 11 01.
Article in English | MEDLINE | ID: covidwho-1377994

ABSTRACT

PURPOSE OF REVIEW: This review highlights literature from the past year and explores the impact on current understanding of celiac disease pathogenesis, diagnosis, and management. RECENT FINDINGS: In contrast to earlier clinical trials, recent data suggests that early gluten introduction may protect against the development of celiac disease. Celiac disease is underdiagnosed, associated with high burden of disease and linked to excess mortality risk, yet, there remains considerable uncertainty regarding the utility of mass screening in asymptomatic individuals. The gut microbiome is increasingly implicated in celiac disease pathogenesis, although the exact mechanism is undefined. Probiotics have been proposed as a disease-modifying option for celiac disease but most studies assessing efficacy are of low-quality. Patients with celiac disease do not appear to be at increased risk of contracting or developing adverse outcomes from COVID-19. Little is known about the pathogenesis of nonceliac gluten sensitivity; however, recent findings suggest an autoimmune basis for the condition. SUMMARY: Current understanding of celiac disease continues to advance, though significant knowledge gaps remain. Large, rigorous, prospectively designed studies are needed to further characterize celiac disease pathogenesis, management and therapeutic options.


Subject(s)
COVID-19 , Celiac Disease , Celiac Disease/diagnosis , Celiac Disease/therapy , Diet, Gluten-Free , Glutens , Humans , SARS-CoV-2
10.
Clin Med (Lond) ; 21(2): 127-130, 2021 03.
Article in English | MEDLINE | ID: covidwho-1357645

ABSTRACT

Coeliac disease (CD) is a common autoimmune-mediated gluten sensitive enteropathy, with a prevalence of around 1%. While the incidence of CD has increased over the last 2 decades, many cases still remain undiagnosed. The presentation of CD is variable and can be subtle, with it being important to explore both gastrointestinal and extra-intestinal features. The cornerstone of management is adherence to a strict gluten free diet, which requires support and education from an expert gastrointestinal dietitian. Persisting symptoms in individuals requires re-evaluation, with repeat duodenal biopsies sometimes required. Refractory CD affects a small subset of individuals with CD, requiring specialist input.


Subject(s)
Celiac Disease , Biopsy , Celiac Disease/diagnosis , Celiac Disease/epidemiology , Celiac Disease/therapy , Diet, Gluten-Free , England/epidemiology , Humans , State Medicine
11.
Eur Rev Med Pharmacol Sci ; 25(12): 4400-4404, 2021 06.
Article in English | MEDLINE | ID: covidwho-1296350

ABSTRACT

OBJECTIVE: Celiac disease (CD) is an autoimmune disorder, characterized by increased susceptibility to bacterial and viral infections. Therefore, the CD patients could be exposed to an increased risk of contracting SARS-CoV-2, a virus for which the WHO declared a pandemic status in March 2020. This study aims to investigate the incidence of SARS-CoV-2 infection in CD patients, to assess the impact of CD on the risk of contracting this virus. PATIENTS AND METHODS: This retrospective multicentric cohort study evaluated 542 celiac patients, who answered a questionnaire concerning both the underlying disease (adherence to the gluten-free diet, residual symptoms) and the possible SARS-CoV-2 infection (swab outcome, presence and characteristics of symptoms and type of treatment received), referring to the period between 20th January 2020 and 27th October 2020. RESULTS: Five patients (0.92%) tested positive; of these, 2 were asymptomatic and 3 developed symptoms of COVID-19. The incidence of SARS-CoV-2 infection in CD patients was not significantly different from the general population. The ratio of positive/diagnostic swabs tends to be higher in CD patients than in the general population (IR: 0.15; 0.06; p=0.06), whereas the number of subjects who performed the swab in this group is significantly lower (IR: 0.06; 0.15; p<0.001). CONCLUSIONS: Although CD patients are more susceptible to infections, the incidence of SARS-CoV-2 infection in our sample was not significantly different from the general population. However, the positive/diagnostic swabs ratio seems to be higher, probably also due to the lower number of patients tested.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Celiac Disease/diagnosis , Celiac Disease/epidemiology , COVID-19/therapy , COVID-19 Testing/methods , Celiac Disease/therapy , Cohort Studies , Diet, Gluten-Free/methods , Humans , Italy/epidemiology , Retrospective Studies
12.
World J Gastroenterol ; 27(12): 1213-1225, 2021 Mar 28.
Article in English | MEDLINE | ID: covidwho-1172998

ABSTRACT

BACKGROUND: We recently demonstrated that the odds of contracting coronavirus disease 2019 (COVID-19) in patients with celiac disease (CeD) is similar to that of the general population. However, how patients with CeD perceive their COVID-19 risk may differ from their actual risk. AIM: To investigate risk perceptions of contracting COVID-19 in patients with CeD and determine the factors that may influence their perception. METHODS: We distributed a survey throughout 10 countries between March and June 2020 and collected data on demographics, diet, COVID-19 testing, and risk perceptions of COVID-19 in patients with CeD. Participants were recruited through various celiac associations, clinic visits, and social media. Risk perception was assessed by asking individuals whether they believe patients with CeD are at an increased risk of contracting COVID-19 when compared to the general population. Logistic regression was used to determine the influencing factors associated with COVID-19 risk perception, such as age, sex, adherence to a gluten-free diet (GFD), and comorbidities such as cardiac conditions, respiratory conditions, and diabetes. Data was presented as adjusted odds ratios (aORs). RESULTS: A total of 10737 participants with CeD completed the survey. From them, 6019 (56.1%) patients with CeD perceived they were at a higher risk or were unsure if they were at a higher risk of contracting COVID-19 compared to the non-CeD population. A greater proportion of patients with CeD perceived an increased risk of contracting COVID-19 when compared to infections in general due to their CeD (56.1% vs 26.7%, P < 0.0001). Consequently, 34.8% reported taking extra COVID-19 precautions as a result of their CeD. Members of celiac associations were less likely to perceive an increased risk of COVID-19 when compared to non-members (49.5% vs 57.4%, P < 0.0001). Older age (aOR: 0.99; 95%CI: 0.99 to 0.99, P < 0.001), male sex (aOR: 0.84; 95%CI: 0.76 to 0.93, P = 0.001), and strict adherence to a GFD (aOR: 0.89; 95%CI: 0.82 to 0.96, P = 0.007) were associated with a lower perception of COVID-19 risk and the presence of comorbidities was associated with a higher perception of COVID-19 risk (aOR: 1.38; 95%CI: 1.22 to 1.54, P < 0.001). CONCLUSION: Overall, high levels of risk perceptions, such as those found in patients with CeD, may increase an individual's pandemic-related stress and contribute to negative mental health consequences. Therefore, it is encouraged that public health officials maintain consistent communication with the public and healthcare providers with the celiac community. Future studies specifically evaluating mental health in CeD could help determine the consequences of increased risk perceptions in this population.


Subject(s)
COVID-19 , Celiac Disease , Aged , COVID-19 Testing , Celiac Disease/diagnosis , Humans , Male , Perception , SARS-CoV-2
14.
Eur J Gastroenterol Hepatol ; 32(12): 1523-1526, 2020 12.
Article in English | MEDLINE | ID: covidwho-1020322

ABSTRACT

OBJECTIVES: Recent guidelines for celiac disease have allowed a biopsy-free approach in endomysial antibodies (EMAs) positive children with high antitransglutaminase (TGA-IgA) titer [>10 time upper limit of normal (ULN)]. Esophagogastroduodenoscopy is still necessary for diagnosis in children with lower title. Because elective pediatric endoscopy has been substantially shouted down during coronavirus disease (COVID-19) pandemic, many children remained undiagnosed - and therefore untreated - for a long time. We aimed to analyze the feasibility and accuracy of a biopsy-free approach in suspected celiac disease children with TGA-IgA values <10 ULN to facilitate the diagnostic process by avoiding endoscopy. METHODS: In this study cohort, we retrospectively analyzed all biopsy-confirmed diagnosis of celiac disease in our center (between 2014 and 2019). The positive predictive value (PPV) of TGA-IgA titers between 5 and 10 ULN and positive EMA in diagnosing celiac disease were determined. Mucosal atrophy and resolution of symptoms after gluten-free diet (GFD) were considered to confirm initial diagnosis. RESULTS: Of 430 celiac disease patients (F: 274; mean age 7.54 years) diagnosed by endoscopy, 84 (F: 46; mean age 8 years) with TGA-IgA between 5 and 10 ULN and positive EMA were identified. The PPV of TGA-IgA between 5 and 10 ULN and positive EMA was 0.93 (95% confidence interval 0.90-0.96). All these children had a symptom resolution and antibodies normalization after GFD. CONCLUSION: During the COVID-19 outbreak, a temporarily reduction of the TGA-IgA threshold for biopsy-sparing approach seems feasible in EMA positive children with TGA-IgA between 5 and 10 ULN.


Subject(s)
Autoantibodies/blood , Betacoronavirus , Celiac Disease/diagnosis , Coronavirus Infections/epidemiology , Pneumonia, Viral/epidemiology , Practice Guidelines as Topic , Transglutaminases/immunology , Autoantibodies/immunology , Biopsy , COVID-19 , Celiac Disease/epidemiology , Celiac Disease/immunology , Child , Comorbidity , Coronavirus Infections/enzymology , Coronavirus Infections/immunology , Endoscopy, Digestive System , Female , Humans , Male , Pandemics , Pneumonia, Viral/enzymology , Pneumonia, Viral/immunology , Retrospective Studies , SARS-CoV-2 , Transglutaminases/blood
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