Investigating the Relationship Between COVID-19 and Celiac Disease. A Dual Research Approach.

Background: Most evidence on the coronavirus disease 2019 (COVID-19) pandemic, has been obtained from web- or telephone-based surveys. In particular, few laboratory data, often incomplete, have been reported on the frequency of COVID-19-related serology at celiac disease (CD) diagnosis or on the effects of COVID-19 on the development of CD-specific autoimmunity. Objectives: The objective of this retrospective cross-sectional case/control study was to: (1) evaluate the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in 78 children and adolescents at CD diagnosis (CD, 44 females, median age 7.4 years); (2) evaluate the frequency of IgA-anti-transglutaminase antibodies (IgA-tTGAbs) in 97 nonceliac patients (50 females, median age 9.0 years) who contracted SARS-CoV-2 infection during the pandemic (February-April 2021). As a control (CTRL) group, we analyzed 141 healthy subjects (79 females, median age 9.8 years) enrolled during the pandemic. Methods: SARS-CoV-2 IgM- and IgG-antibodies were detected by chemiluminescent microparticle immunoassays. IgA-tTGAbs were detected by a fluid-phase radioimmunoassay. Results: Six out of 78 (7.7%) CD patients tested positive for SARS-CoV-2Abs, with a frequency not significantly different from CTRL subjects (9.2%). None of the 97 nonceliac COVID-19 patients tested positive for IgA-tTG antibodies. Conclusion: These 2 distinct research approaches showed (1) similar frequencies of SARS-CoV-2 immunoreactivities in CD patients and CTRL subjects and, (2) no ability of SARS-CoV-2 to induce a CD-specific immune response, at least in the 3-4 months following SARS-CoV-2 infection.

The Influence of Ketogenic Diet on Gut Microbiota: Potential Benefits, Risks and Indications.

The ketogenic diet (KD) restricts carbohydrate consumption, leading to an increase in ketone bodies, such as acetoacetate, ß-hydroxybutyrate, and acetone, which are utilized as energy substrates. This dietary approach impacts several biochemical processes, resulting in improved clinical management of various disorders, particularly in childhood. However, the exact mechanisms underlying the efficacy of KD remain unclear. Interestingly, KD may also impact the gut microbiota, which plays a pivotal role in metabolism, nutrition, and the development of the immune and nervous systems. KD has gained popularity for its potential benefits in weight loss, blood sugar control, and certain neurological conditions. This narrative review sums up KD-related studies published over 30 years. While short-term studies have provided valuable insights into the effects of KD on the gut microbiota, persistent uncertainties surround its long-term efficacy and potential for inducing dysbiosis. The significant influence of KD on epigenetic mechanisms, intracellular pathways, and gut microbial composition underscores its potential as a therapeutic choice. However, a judicious consideration of the potential risks associated with the strict adherence to a low-carbohydrate, high-fat, and high-protein regimen over prolonged periods is imperative. As KDs gain popularity among the adolescent and young adult demographic for weight management, it becomes imperative to undertake additional research to comprehensively assess their impact on nutritional status and gut microbiota, ensuring a holistic and sustainable approach to medical nutrition.

Refeeding Syndrome in Pediatric Age, An Unknown Disease: A Narrative Review.

Refeeding syndrome (RS) is characterized by electrolyte imbalances that can occur in malnourished and abruptly refed patients. Typical features of RS are hypophosphatemia, hypokalemia, hypomagnesemia, and thiamine deficiency. It is a potentially life-threatening condition that can affect both adults and children, although there is scarce evidence in the pediatric literature. The sudden increase in food intake causes a shift in the body's metabolism and electrolyte balance, leading to symptoms such as weakness, seizures, and even heart failure. A proper management with progressive increase in nutrients is essential to prevent the onset of this condition and ensure the best possible outcomes. Moreover, an estimated incidence of up to 7.4% has been observed in pediatric intensive care unit patients receiving nutritional support, alone or as an adjunct. To prevent RS, it is important to carefully monitor feeding resumption, particularly in severely malnourished individuals. A proper strategy should start with small amounts of low-calorie fluids and gradually increasing the calorie content and amount of food over several days. Close monitoring of electrolyte levels is critical and prophylactic use of dietary supplements such as thiamine may be required to correct any imbalances that may occur. In this narrative review, we aim to provide a comprehensive understanding of RS in pediatric clinical practice and provide a possible management algorithm.

Ketogenic diet in children and adolescents: The effects on growth and nutritional status.

The ketogenic diet is known to be a possible adjuvant treatment in several medical conditions, such as in patients with severe or drug-resistant forms of epilepsy. Its use has recently been increasing among adolescents and young adults due to its supposed weight-loss effect, mediated by lipolysis and lowered insulin levels. However, there are still no precise indications on the possible use of ketogenic diets in pediatric age for weight loss. This approach has also recently been proposed for other types of disorder such as inherited metabolic disorders, Prader-Willi syndrome, and some specific types of cancers. Due to its unbalanced ratio of lipids, carbohydrates and proteins, a clinical evaluation of possible side effects with a strict evaluation of growth and nutritional status is essential in all patients following a long-term restrictive diet such as the ketogenic one. The prophylactic use of micronutrients supplementation should be considered before starting any ketogenic diet. Lastly, while there is sufficient literature on possible short-term side effects of ketogenic diets, their possible long-term impact on growth and nutritional status is not yet fully understood, especially when started in pediatric age.

Neurological impairment and malnutrition in children: The role of home enteral nutrition in real life.

Objective: Recent decades have brought an increased survival of children with Neurologic Impairment (NI) but malnutrition and digestive comorbidity remain important challenges to face. We designed the present study to assess the course of nutritional status following standardized Home Enteral Nutrition (HEN) program and to evaluate impact of changing mode of feeding, as a part of overall multidisciplinary management, on digestive co-morbidity as Gastro-Esophageal Reflux Disease (GERD), Oropharyngeal Dysphagia (OPD), constipation and airway aspiration. Methods: We performed a retrospective analysis on NI children entered into Institutional HEN program due to NI disorders between January 2011 and 2019. Demographic, anthropometric characteristics (BMI z-score and weight for age z-score) and symptoms (GERD, OPD constipation and airway aspiration) were collected at the enrolment and during the follow up. Results: We enrolled 402 patients (median age: 39 months); overall survival was 97%. Nutritional status was significantly improved by HEN; in particular growth profile significantly changed within the first 2 years following HEN beginning; GERD and airways aspirations decreased after HEN beginning. Constipation and OPD remained unchanged over time. Conclusions: Malnutrition and digestive complaints are distinctive features of NI children. Nutritional status improve after 2 years from the beginning of standardized nutritional interventions. Overall multidisciplinary care, including standardized HEN protocols, seems to also impact on GERD and airway aspirations, which can decrease over time. It is possible that constipation and OPD, unchanged over time, are more dependent on underlying diseases than on overall treatments.

Enteral formula compared to Nissen-Fundoplication: Data from a retrospective analysis on tolerance, utility, applicability, and safeness in children with neurological diseases.

Objectives and study: Approximately 46-90% of children with neurological disorders (NDs) suffer from gastrointestinal diseases, such as gastro-esophageal reflux disease (GERD), constipation, or malnutrition. Therefore, enteral feeding is often necessary to achieve nutritional requirements. The treatment of GERD could be based on pharmacological therapy, nutritional treatment (changing the type of formula), or surgical treatment (Nissen Fundoplication, NF). The aim of this study was to describe and compare resource consumption between NE based on different formulas and NF in patients with ND. Methods: We performed a retrospective analysis on all children with neurological damage (age: 29 days-17 years) treated from January 2009 to January 2019 due to nutritional problems and food and/or gastrointestinal intolerances. For all patients, demographic and anthropometric characteristics, symptoms, type of nutrition (formula and enteral access), and number and type of outpatient or emergency room visits were collected. Patients with <24 months of age at the closing of the database and with <24 months of follow-up were excluded. Results: Out of 376 children, 309 children (M: 158; median age: 4 IQR 1-10) were enrolled, among which, 65 patients (NF group M: 33; median age: 5.3 IQR 1.8-10.7) underwent NF. Vomit, GERD, and dysphagia were more represented in the NF group (p < 0.05). Our analysis shows that the NF group seems to present a lower number of hospitalization and a lower number of visits for non-GI disorders, but a higher number of visits for GI disorders compared to non-NF. In the NF group, a higher prevalence of the use of amino-acid-based formula and free diet is observed, with a trend for the lower prevalence of casein-based or whey+casein-based formula (Fisher test p = 0.072). The median cost of a patient enrolled in the database is € 19,515 ± 540 ($ 20,742.32 ± 573.96) per year, with no significant difference between the two groups. Regarding formula, at baseline, 76 children consumed a free diet, 24 a casein-based formula, 139 a whey+casein-based formula, 46 a whey-based formula, and 24 an amino-acid-based formula. Conclusions: In conclusion, compared to EN, NF may not improve the clinical aspect and related costs in children with NDs. Considering the psychological and QoL burden for patients, in a "step-up" strategy, EN could be proposed as an efficient alternative to NF.

Cohort profile: Celiac disease genomic, environmental, microbiome and metabolome study; a prospective longitudinal birth cohort study of children at-risk for celiac disease.

The Celiac Disease Genomic, Environmental, Microbiome and Metabolomic (CDGEMM) study is an international prospective birth cohort in children at-risk of developing celiac disease (CD). The CDGEMM study has been designed to take a multi-omic approach to predicting CD onset in at-risk individuals. Participants are required to have a first-degree family member with biopsy diagnosed CD and must be enrolled prior to the introduction of solid food. Participation involves providing blood and stool samples longitudinally over a period of five years as well as answering questionnaires related to the participant, their family, and environment. Recruitment and data collection have been ongoing since 2014. As of 2022 we have a total of 554 participants and the average age of the cohort is 56.4 months. A total of 54 participants have developed positive antibodies for CD and 31 have confirmed CD. Approximately 80% of the 54 participants with CD have developed it by 3 years of age. To date we have identified several microbial strains, pathways, and metabolites occurring in increased abundance and detected before CD onset, which have previously been linked to autoimmune and inflammatory conditions while others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects. Our ongoing analysis includes expanding our metagenomic and metabolomic analyses, evaluating environmental risk factors linked to CD onset, and mechanistic studies investigating how alterations in the microbiome and metabolites may protect against or contribute to CD development.

Role of age in dynamics of autoantibodies in pediatric Celiac disease.

BACKGROUND: Celiac disease (CD) is characterized by elevated serum titers of autoantibodies IgA anti-tissue transglutaminase 2 (TGA-IgA) and IgA anti-endomysial (EMA), with small bowel mucosa atrophy. We evaluated age differences between CD children exhibiting variable antibody titers at diagnosis. METHODS: CD children diagnosed between January 2014 and June 2019, according to 2012 ESPGHAN guidelines were studied. All had EMA and TGA-IgA measurements, while a proportion of them underwent esophagogastroduodenoscopy (EGD). Patients were grouped based on serum TGA-IgA titers normalized to the upper limit of normal (ULN) and differences in median age (years) assessed by analysis of variance (ANOVA) and creation of orthogonal contrasts. RESULTS: CD was diagnosed in 295 subjects (median age: 4.4 [IQR: 2.60-8.52]) with a biopsy sparing protocol (high titer: ≥ 10xULN) and in 204 by EGD biopsy. Of the latter, 142 (median age: 8.5 [IQR: 5.81-11.06]) and 62 (median age: 9.5 [IQR: 6.26-12.76]) had a low (< 5xULN) and a moderate (≥ 5 < 10xULN) TGA-IgA titer, respectively. Potential CD was diagnosed in 20 patients (median age: 3.6 [IQR: 2.47-6.91]). The median age was significantly lower in the no-biopsy group (ANOVA: F(3, 516) = 25.98, p < .001) than in low- and moderate titer groups (p < 0.0001), while there was no statistical difference between biopsy-sparing and potential CD groups. CONCLUSION: CD patients with greatly elevated antibody titers (≥ 10xULN) were diagnosed at an earlier age than those with lower titers. This may indicate that an increase in TGA-IgA is independent of age and suggests a polarization of autoimmunity in younger individuals with higher serum antibody levels.

Early Antibody Dynamics in a Prospective Cohort of Children At Risk of Celiac Disease.

INTRODUCTION: The purpose of this study was to identify possible serum biomarkers predicting celiac disease (CD) onset in children at risk. METHODS: A subgroup from an ongoing, international prospective study of children at risk of CD was classified according to an early trajectory of deamidated gliadin peptides (DGPs) immunoglobulin (Ig) G and clinical outcomes (CD, potential CD, and CD autoimmunity). RESULTS: Thirty-eight of 325 children developed anti-tissue transglutaminase IgA antibody (anti-tTG IgA) seroconversion. Twenty-eight of 38 children (73.6%) showed an increase in anti-DGPs IgG before their first anti-tTG IgA seroconversion. DISCUSSION: Anti-DGPs IgG can represent an early preclinical biomarker predicting CD onset in children at risk.

Prevalence and detection rate of celiac disease in Italy: Results of a SIGENP multicenter screening in school-age children.

BACKGROUND: Celiac disease is a common lifelong disorder. Recent studies indicate that the number of clinically detected cases has increased over the last decades, however little is known about changes in the prevalence and the detection rate of celiac disease. AIM: To evaluate the current prevalence and detection rate of celiac disease in Italy by a multicenter, mass screening study on a large sample of school-age children. METHODS: children aged 5-11 years were screened at school by HLA-DQ2 and -DQ8 determination on a drop of blood in six Italian cities; total serum IgA and IgA anti-transglutaminase were determined in children showing HLA-DQ2 and/or -DQ8 positivity. Diagnosis of celiac disease was confirmed according to the European guidelines. RESULTS: 5994 children were eligible, 4438 participated and 1873 showed predisposing haplotypes (42.2%, 95% CI=40.7-43.7). The overall prevalence of celiac disease was 1.65% (95% CI, 1.34%-2.01%). Only 40% of celiac children had been diagnosed prior to the school screening. Symptoms evoking celiac disease were as common in celiac children as in controls. CONCLUSION: In this multicenter study the prevalence of celiac disease in school-age Italian children was one of the highest in the world. Determination of HLA predisposing genotypes is an easy and fast first-level screening test for celiac disease. Without a mass screening strategy, 60% of celiac patients remain currently undiagnosed in Italy.

Management of Nutritional Needs in Pediatric Oncology: A Consensus Statement.

Malnutrition, intended as both overnutrition and undernutrition, is a common problem in children with cancer, impacting quality of life as well as survival. In addition, nutritional imbalances during childhood can significantly affect proper growth. Nevertheless, there is currently a lack of a systematic approach to this issue in the pediatric oncology population. To fill this gap, we aimed to provide practice recommendations for the uniform management of nutritional needs in children with cancer. Twenty-one clinical questions addressing evaluation and treatment of nutritional problems in children with cancer were formulated by selected members from four Italian Association of Pediatric Hematology and Oncology (AIEOP) centers and from the Survivorship Care and Nutritional Support Working Group of Alliance Against Cancer. A literature search in PubMed was performed; during two consensus meetings, all recommendations were discussed and finalized using the nominal group technique. Members representing every institution voted on each recommendation. Finally, recommendations were approved by all authors.

Real food in enteral nutrition for chronically ill children: overview and practical clinical cases.

BACKGROUND: Many feeding strategies may be used in chronically ill children on enteral nutrition. Interest is currently growing in real food-based enteral nutrition. A new tube feeding formula with real food ingredients is currently commercially available in Europe. CASE REPORTS: By focusing on four clinical cases, this article illustrates the use of a tube feeding formula with real food ingredients in pediatric patients with various complex conditions. The formula contains a milk-based mixture of peas, green beans, peaches, carrots, and chicken, and provides 1.2 kcal/ml. It was offered under medical supervision and after full consideration of all feeding options. CONCLUSIONS: Formula choice appears to be based on clinical experience and must be individualized to patients' characteristics and needs. Real food-containing formulas seem to improve tolerance and feeding outcomes as well as promote family inclusion and mealtime engagement, but further studies are warranted.

Five-Year Inpatient Management of Teenagers With Anorexia Nervosa: Focus on Nutritional Issues.

OBJECTIVES: In patients with Anorexia Nervosa (AN) malnutrition can lead to life-long nutritional treatments. The refeeding process can combine natural feeding (NF) with specific nutritional strategies, including oral nutritional supplements (ONS) and nasogastric feeding (NGF). Aims of the present study were to assess the efficacy of hospital protocol and identify the most effective inpatient nutritional strategies for weight restoration. METHODS: All patients hospitalized from April 2015 to April 2020 were enrolled. According to hospital protocol, NF was proposed to all patients; ONS were combined with NF if caloric intake was <70% of the requirements and NGF was added if caloric intake did not reach 30% in the first week from admission. RESULTS: Overall, 186 patients [M = 20; median age 14 (interquartile range 1316)] were included. Nutritional issues were the main indication to admission (56.6%). A significant effect of combination treatment, with a shorter duration of hospitalization when using ONS with NGF in addition to NF was found (ß: -20.28 [95% confidence interval -34.92:-5.65], P  < 0.001). Only one patient showed a significant but limited increase of liver enzymes. CONCLUSIONS: We provide a safe and effective standardized protocol to treat the malnutrition of teenagers with AN in an inpatient setting. Malnutrition was the most important cause of admission, and more than half of the patients admitted were severely malnourished. The combination of NF, ONS, and NGF was the most effective strategy to achieve the weight restoration; however, this result should be validated on larger series of patients treated with NGF and NF.

Maintenance Therapy With the Lowest Effective Dose of Oral Viscous Budesonide in Children With Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an immune-mediated condition characterized by symptoms of esophageal dysfunction and an eosinophilic inflammation of the esophagus.1 Swallowed topical steroids represent one of the possible strategies for inducing and maintaining remission in EoE.2 To date, a validated maintenance strategy has yet to be defined, especially in children. The available evidence suggests decreasing the dose after a successful induction therapy.3 No study has reported the efficacy of a continuous progressive dose reduction; thus, it is unknown if all patients need to use the same dosages and for how long.4,5.

A new double immunohistochemistry method to detect mucosal anti-transglutaminase IgA deposits in coeliac children.

BACKGROUND: Intestinal transglutaminase (TG2) IgA deposits represent early marker of coeliac disease (CeD) and can predict the evolution towards intestinal atrophy. AIMS: To validate a double immunohistochemistry method for the determination of intestinal TG2 IgA deposits on formalin-fixed paraffin-embedded biopsies. METHODS: Immunohistochemistry was tested on: 1) children with overt CeD [persistently positive serum IgA anti-tissue transglutaminase type 2 (TGA-IgA) with moderate or low titer, and histological findings of CeD]; 2) potential CeD (persistently positive serum TGA-IgA and normal intestinal mucosa) and 3) controls (negative serum TGA-IgA and normal intestinal mucosa). RESULTS: Samples from 61 children were analyzed (32 overt CeD, 14 potential CeD, and 15 controls). Deposits appeared as focal, multifocal, or confluent extracellular foci of red and brown staining colocalization in the sub-epithelium and around mucosal vessels. Deposits were present in all 32 children with overt CeD and in 9/14 potential CeD. Deposits were never observed in the 15 controls. Patients with higher serum level of TGA-IgA and with mucosal atrophy showed mostly a multifocal/diffuse pattern of deposits distribution. The bulb appeared most severely involved. In potential CeD deposits showed mainly a focal distribution. CONCLUSION: Our results indicate double immunohistochemistry as promising diagnostic tool to improve diagnosis of CeD.

Microbiome signatures of progression toward celiac disease onset in at-risk children in a longitudinal prospective cohort study.

Other than exposure to gluten and genetic compatibility, the gut microbiome has been suggested to be involved in celiac disease (CD) pathogenesis by mediating interactions between gluten/environmental factors and the host immune system. However, to establish disease progression markers, it is essential to assess alterations in the gut microbiota before disease onset. Here, a prospective metagenomic analysis of the gut microbiota of infants at risk of CD was done to track shifts in the microbiota before CD development. We performed cross-sectional and longitudinal analyses of gut microbiota, functional pathways, and metabolites, starting from 18 mo before CD onset, in 10 infants who developed CD and 10 matched nonaffected infants. Cross-sectional analysis at CD onset identified altered abundance of six microbial strains and several metabolites between cases and controls but no change in microbial species or pathway abundance. Conversely, results of longitudinal analysis revealed several microbial species/strains/pathways/metabolites occurring in increased abundance and detected before CD onset. These had previously been linked to autoimmune and inflammatory conditions (e.g., Dialister invisus, Parabacteroides sp., Lachnospiraceae, tryptophan metabolism, and metabolites serine and threonine). Others occurred in decreased abundance before CD onset and are known to have anti-inflammatory effects (e.g., Streptococcus thermophilus, Faecalibacterium prausnitzii, and Clostridium clostridioforme). Additionally, we uncovered previously unreported microbes/pathways/metabolites (e.g., Porphyromonas sp., high mannose-type N-glycan biosynthesis, and serine) that point to CD-specific biomarkers. Our study establishes a road map for prospective longitudinal study designs to better understand the role of gut microbiota in disease pathogenesis and therapeutic targets to reestablish tolerance and/or prevent autoimmunity.

COVID-19 and celiac disease: A pathogenetic hypothesis for a celiac outbreak.

BACKGROUND: A growing body of evidence supports the intestinal trophism of SARS-CoV-2, with ciliated cells and intestinal enterocytes being target cells because of the high expression of ACE2 and TMPRSS2. Indeed, COVID-19 promotes a "cytokine storm" in the intestinal mucosa: the resulting epithelial damage leads to increased barrier permeability, allowing the passage of gliadin in the intestinal lamina. METHODS: Based on current literature, we hypothesize the role of COVID-19 as a potential trigger factor for celiac disease in predisposed patients. CONCLUSIONS: Genetically predisposed patients could be more likely to develop celiac disease following SARS-CoV-2 infection, making COVID-19 a candidate culprit for a potential outbreak of celiac disease in the forthcoming future.

Association between Elevated TGA-IgA Titers and Older Age at Diagnosis with Absence of HBV Seroconversion in Celiac Children.

Patients with celiac disease can have a low rate of protective hepatitis B (HBV) antibody titers after vaccination. We aimed to evaluate the HBV seroconversion in celiac disease (CD) children at the time of diagnosis as well as to identify the presence of possible predictive factors. Celiac disease children were prospectively enrolled and tested for antibodies against the S protein of HBV (HBsAg) at time of diagnosis between January 2009 and February 2020. Based on the serologic response to the vaccine, "responders" and "non-responders" were identified. Statistical analysis has been performed through R statistical software (3.5.1 version, R core Team) Of 96 CD children evaluated, 41.7% (n = 40) showed non-protective or absent antibody titers against HBV. Elevated IgA-antibodies against transglutaminase 2 (TGA-IgA) values and older age at diagnosis were associated with an absent seroconversion to HBV vaccine, while presenting symptoms were not significant. An elevated prevalence of absent seroconversion to HBV vaccine exists in this cohort of CD patients at the time of disease diagnosis. Elevated TGA-IgA titers and older age at diagnosis seem to negatively predict seroconversion. Further studies are needed to identify the real profile of "non-responders", aiming to organize surveillance and eventual revaccination strategy.

ESPGHAN 'biopsy-sparing' guidelines for celiac disease in children with low antitransglutaminase during COVID-19.

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.