Lymphoproliferation- a clue towards an underlying monogenic disorder of immune dysregulation- a retrospective analysis from a single center in India

Background: Lymphoproliferation is the persistent proliferation of lymphoid cells and it's incidence in inborn errors of immunity varies from 0.7 to 18%. Material(s) and Method(s): This is a retrospective analysis of patients referred to the department of Immunology, B. J. Wadia Hospital for Children, Mumbai between March 2017 to December 2022. Inclusion criteria consisted of 3 months duration of significant lymphadenopathy and/or splenomegaly or history of lymphoma. The clinical characteristics, laboratory and molecular findings of the included patients were analyzed. Result(s): A total of 66 patients were included. There was a male preponderance with male:female ratio of 25:8. Median age of onset of lymphoproliferation was 4.75 years(Range 1 year to 60 years). Splenomegaly was seen in 75%. Infections included recurrent pneumonia (14/66), recurrent ear infections(5/66), COVID(4/66), one episode of pneumonia(6/66), herpes zoster(3/66), recurrent subcutaneous abscess (3/66), abdominal koch(3/66), chronic sinusitis(2/66), dermatophytosis(2/66), esophageal candidiasis(2/66), recurrent malaria(1/66), recurrent varicella(1/66), cryptococcal meningitis(1/66), gram negative sepsis(1/66), BCG adenitis(1/66), pseudomonas osteomyelitis(1/66), impetigo (1/66), pseudomonas urinary tract infection (1/66), chicken pox(1/66), herpes keratitis(1/66), dengue(1/66), Other manifestations included Evans plus phenotype(10/66), Evans phenotype(8/66), Autoimmune hemolytic anemia(5/66), bronchiectasis(5/66), Type 1 diabetes(3/66), hyper reactive airway disease(2/66), inflammatory bowel disease(4/66), autoimmune thrombocytopenia(2/66), stroke(3/66), hemophagocytic lymphohistiocytosis(2/66), hypertriglyceridemia(2/66), hypothyroidism(2/66), celiac disease(1/66), Type 2 diabetes(1/66), autoimmune encephalitis(1/66), autoimmune hepatitis(2/66), anti-parietal cell antibody(1/66), arthritis(1/66), autoimmune enteropathy(1/66), systemic lupus erythromatosus(1/66), primary biliary cirrhosis requiring liver transplant(1/66), nephrotic syndrome(1/66), lymphoedema(1/66), hypersplenism(1/66), recurrent oral ulcers(1/66), gout(1/66), dermatitis(1/66), ovarian teratoma(1/66), alopecia areata(1/66). Hodgkin's lymphoma(HL) was the most common malignancy(9/66), followed by non Hodgkin lymphoma(NHL)(6/66), transformation from NHL to HL(1/66), Burkitt to T-cell lymphoma(1/66), HL to DLBCL(1/66), HL to anaplastic T-cell lymphoma(1/66). EBV driven lymphoproliferation was seen in biopsy of21/66. Genetic testing showed mutations in LRBA(11/66), PIK3CD(5/66), CTLA4(3/66), TET2(2/66), IL2RA (1/66), IL12RB1(1/66), BACH2(1/66), PRKCD(1/66), TNFSFR13B(1/66), TNFAIP3(1/66), FAS(2/66), FASL(1/66), Caspase8(1/66), CARD11(1/66), RTEL1(1/66), AICD(1/66), PIK3R1(1/66), IKBKB(1/66). Treatment included IVIG, chemotherapy, rituximab, sirolimus, abatacept, HSCT. Conclusion(s): All children with persistent lymphoproliferation, with or without autoimmunity and/or infections should be worked up for an underlying monogenic disorder of immune dysregulation. Lymphomas presenting at abnormal site and/or age, relapse and EBV driven lymphomas require further evaluation. Presence of monogenic cause helps in providing targeted therapy.Copyright © 2023 Elsevier Inc.

Coronavirus disease 2019 and gastrointestinal disorders in children.

During the past 3 years, the coronavirus disease 2019 (COVID-19) pandemic has had a great impact on people all over the world. However, it has become evident that disease manifestations and severity differ across age groups. Most children have a milder disease course than adults but possibly more pronounced gastrointestinal (GI) symptoms. Given the child's developing immune system, the impact of COVID-19 on disease development may differ compared to adults. This study reviews the potential bi-directional relationship between COVID-19 and GI diseases in children, focusing on common pediatric conditions such as functional GI disorders (FGID), celiac disease (CeD), and inflammatory bowel disease (IBD). Children with GI diseases, in general, and CeD and IBD, in particular, do not seem to have an increased risk of severe COVID-19, including risks of hospitalization, critical care need, and death. While infections are considered candidate environmental factors in both CeD and IBD pathogenesis, and specific infectious agents are known triggers for FGID, there is still not sufficient evidence to implicate COVID-19 in the development of either of these diseases. However, given the scarcity of data and the possible latency period between environmental triggers and disease development, future investigations in this field are warranted.

Autoimmune Enteropathy (AIE) in a Patient Diagnosed with Thymoma: A Case Report

Introduction: Autoimmune enteropathy (AIE) is a very rare immune disorder that mainly attacks the gastrointestinal tract by T-cell. The full pathology mechanism is not clear. Typically, characterized by intractable diarrhea and nutritional malabsorption with extra-intestinal manifestations. The proposed diagnostic criteria include small bowel villous atrophy not responding to diet restriction, circulating gut epithelial cell autoantibodies (GECA), and lack of immunodeficiency. We describe a case of AIE with extensive GI involvement, presenting in a 60-year-old patient diagnosed with Type AB thymoma. Case Description/Methods: Our gentleman with a history of Covid-19 complicated with pulmonary embolism and an incidental finding of malignant thymoma. A CT-guided biopsy was consistent with undifferentiated malignant thymoma supported by immunohistochemistry staining. Subsequently, complicated severe diarrhea erupted with significant weight loss. Conservative management, antibiotics, and diet restriction were ineffective. Diagnostic work-up was unremarkable except for anti-enterocytes antibodies (AEA) and anti-goblet cells antibodies (AGA). Bowel biopsy revealed villous blunting, loss of Paneth cells, and minimal intraepithelial lymphocytosis with no evidence of crypt abscesses. Corticosteroid and Octreotide have helped the patient's diarrhea. Thoracoscopy thymectomy performed with radiation therapy due to local and lymphovascular invasion. Discussion(s): AIE characterized by severe villous blunting with the absence of goblet cells and Paneth cells, intraepithelial lymphocytosis, and increased crypt apoptosis. In comparison, graft vs host disease lack crypt abscesses, celiac disease shows increase in the intraepithelial lymphocytosis with intact goblet and Paneth cells, whereas inflammatory bowel disease has intact goblet and Paneth cells, and CVID characterized by absence of plasma cell in the lamina propria. The presences of the GECA are nonspecific but it may help in confirming the diagnosis or may predict the prognosis and recurrence. Only AGA has been reported in IBD. Neither has been observed in celiac disease. The low incidence of AIE and the limited existing literature available on the optimal guidance in management. Oral nutritional supplementation as well as total parenteral nutrition is helpful. The target is to control diarrhea and optimize the nutritional status before surgery. The main treatment is thymectomy.

The risk for celiac disease after Covid-19 infection.

BACKGROUND: Celiac disease (CD) is an autoimmune disease leading to gastrointestinal symptoms and mineral deficiencies. The pathogenetic mechanisms, besides the clear HLA association, are elusive. Among environmental factors infections have been proposed. Covid-19 infection results in a systemic inflammatory response that often also involves the gastrointestinal tract. The aim of the present study was to investigate whether Covid-19 infection could increase the risk for CD. PATIENTS AND METHODS: All patients, both children and adults, in the county Skåne (1.4 million citizens) in southern Sweden with newly diagnosed biopsy- or serology-verified CD or a positive tissue transglutaminase antibody test (tTG-ab) during 2016-2021 were identified from registries at the Departments of Pathology and Immunology, respectively. Patients with a positive Covid-19 PCR or antigen test in 2020 and 2021 were identified from the Public Health Agency of Sweden. RESULTS: During the Covid-19 pandemic (March 2020 - December 2021), there were 201 050 cases of Covid-19 and 568 patients with biopsy- or serology-verified CD or a first-time positive tTG-ab tests, of which 35 patients had been infected with Covid-19 before CD. The incidence of verified CD and tTG-ab positivity was lower in comparison to before the pandemic (May 2018 - February 2020; 22.5 vs. 25.5 cases per 100 000 person-years, respectively, incidence rate difference (IRD) -3.0, 95% CI -5.7 - -0.3, p = 0.028). The incidence of verified CD and tTG-ab positivity in patients with and without prior Covid-19 infection was 21.1 and 22.4 cases per 100 000 person-years, respectively (IRD - 1.3, 95% CI -8.5-5.9, p = 0.75). CONCLUSIONS: Our results indicate that Covid-19 is not a risk factor for CD development. While gastrointestinal infections seem to be an important part of the CD pathogenesis, respiratory infections probably are of less relevance.

COVID-19 and celiac disease: a review.

The aim of this review is to broadly cover how the COVID-19 pandemic has affected individuals with celiac disease, including perceived risk, risk of contraction or severe infection, considerations regarding vaccination, access to gluten-free food during the pandemic, and possible long-term changes to the practice of celiac disease management spurred by the pandemic. While initially there was increased perceived risk about COVID-19 in the celiac disease population, studies have found that individuals with celiac disease are not at an increased risk of contracting or having a severe course compared to the general population. There is not yet evidence that COVID-19 infection will lead to an increase in celiac disease incidence, though more research on this topic with longer-term follow-up is necessary to make this determination. Limited access to in-person visits led to an increase in telemedicine, which was adopted swiftly by this patient population and may offer improved access in the long term. In summary, individuals with celiac disease do not appear to be at an increased risk of contracting COVID-19 or having a more severe disease course.

8th International Multidisciplinary Course on Iron Deficiency

The proceedings contain 37 papers. The topics discussed include: Are normal iron and hemoglobin levels needed for acquiring innate immunity and optimizing responses to COVID-19 vaccination?;management of iron deficiency in PBM: the pandemic's barriers;iron deficiency and celiac disease;treating iron deficiency in patients with ulcerative colitis;iron deficiency anemia in children: risk factors, prevention, diagnosis and therapy;iron therapy in children with inflammatory bowel disease (IBD);iron supplementation in pediatric patients with primary iron deficiency anemia: An IRIDA clinical case;iron-deficiency anemia and functional capacity in post-cardiac surgical patients: comparison between two martial treatments;iron prophylaxis in pregnant women and pregnancy outcomes;patient blood management: Anemia in obstetrics;and clinical safety and efficacy of iron supplementation in cancer patients.

Copper Deficiency Mimicking Myelodysplastic Syndrome: Zinc Supplementation in the Setting of COVID-19

While copper deficiency is rare, it can have serious consequences, including pancytopenia and neuropathy. This treatable micronutrient deficiency can present very similarly to myelodysplastic syndrome (MDS), a group of myeloid neoplasms which can carry devastating prognoses. Copper deficiency is an essential differential diagnosis in suspected MDS, as it can present with similar laboratory findings, bone marrow biopsy, and clinical picture. While copper deficiency has multiple potential causes, it typically occurs in patients with a predisposing gastrointestinal pathology. One possible cause of copper deficiency is zinc overload. Interestingly, zinc over-supplementation has been prevalent during the COVID-19 pandemic, as some believe that zinc can help prevent COVID-19 infection. Multiple case reports have illustrated the similarities between copper deficiency and MDS. They have also highlighted zinc over-supplementation as a potential cause. The following case report is unique in that our patient lacked gastrointestinal pathology. He still presented with the clinical and laboratory findings of MDS in the setting of copper deficiency. These include anemia, leukopenia, fatigue, and neuropathy. Further, this deficiency was caused by zinc over-supplementation in efforts to prevent COVID-19. The deficiency and the accompanying symptoms were treated with copper supplementation and cessation of zinc intake.

News

This section offers gastrointestinal health-related news briefs as of February 1, 2023, including a study which found that plant-based diet could reduce bowel cancer risk in men, a study which showed that the COVID-19 virus may have a profound effect on the gut microbiome balance, and the call by Coeliac UK for manufacturers to sign up for its labelling scheme in support of research which found that 76% of gluten-free consumers want to be labelled with the Crossed Grain trademark.

SARS-CoV-2 induction and COVID-19 manifestations related to autoimmune gastrointestinal diseases

The COVID-19 usually starts with respiratory symptoms and signs, but extrapulmonary presentations are continuously reported. Interestingly, the human gut occupies a major part of the list. The human intestine is a target organ for SARS-CoV-2. Gastrointestinal complaints like abdominal pains, diarrhea, nausea, vomiting, and hematochezia are the most prevalent. Hepatobiliary like transaminasemia-hepatitis, cholestasis-Jaundice, cholecystitis, and even hepatic failure were reported, as well as pancreatitis. The abdominal clinical symptoms can present the only indicator of COVID-19. Higher awareness of those symptoms may predict the progression to more severe disease, complications, and long covid complaints, along the road. Several pathophysiological mechanisms that facilitate SARS-CoV-2 adhesion, penetration, proliferation, and host cellular damage are described. Finally, SARS-CoV-2 might impact gut autoimmune conditions like inflammatory bowel and celiac diseases, but no cause-and-effect relations were depicted concerning their induction or initiation. © 2023 Elsevier Inc. All rights reserved.

Celiac Disease and the Gluten Free Diet during the COVID-19 Pandemic: Experiences of Children and Parents.

The COVID-19 pandemic perturbed the everyday life of children and those with chronic illnesses, along with the lives of their families. Patients with celiac disease (CD) follow a strict gluten-free diet (GFD), and gluten ingestion is associated with negative health outcomes. The aim of this study was to investigate the experiences of children with CD and their families concerning their GFD, symptoms and CD management during the first period of the COVID-19 pandemic. A cross-sectional questionnaire-based study was performed including 37 Dutch pediatric patients with CD, along with their parents. The majority reported good compliance to the GFD and stated that the diet was easier to follow during the pandemic, mainly due to eating more meals in the home. Some discovered a greater variety of GF products by utilizing online shopping, potentially increasing the financial burden of the GFD. Concerning general dietary habits, 21.6% reported a healthier eating pattern, in contrast to 37.8% and 10.8% who consumed more unhealthy snacks and fewer fruits and vegetables, respectively, than normal during the pandemic. The natural experiment of the COVID-19 pandemic provides valuable information regarding the management of pediatric CD. Education on healthy dietary patterns is important, especially for children with restrictive diets, and the findings of this study show that there is room for improvement in this respect, regardless of the current pandemic.

Prevalence and clinical outcomes of COVID-19 in patients with pre-existing celiac disease: A systematic review and meta-analysis.

There is a scarcity of scientific evidence addressing the outcomes of COVID-19 in celiac disease (CD) patients. This systematic review and meta-analysis aimed to evaluate the correlation between pre-existing CD and COVID-19. A rigorous literature search was conducted using multiple databases. All eligible observational studies were included from around the globe. The random effect model calculated the pooled prevalence and associated 95% confidence intervals (CI). Mantel-Haenszel odds ratios were produced to report the overall effect size using random effect models for severity and mortality outcomes. Funnel plots, Egger regression tests, and Begg-Mazumdar's rank correlation test were used to appraise publication bias. Data from 11 articles consisting of 44,378 CD patients were obtained. Overall pooled random-effects estimate of SARS-CoV-2 infection in CD patients was 4.25% (95% CI, I2  = 98%). Our findings also indicated that pre-existing CD was not associated with an increased risk of hospitalisation with COVID-19 illness (OR = 1.04, 95% CI 0.87-1.24, I2  = 0%) and mortality due to illness (OR = 0.92, 95% CI 0.56-1.5, I2  = 45%) compared with patients without pre-existing CD. No significant publication bias was evident in the meta-analysis. The preliminary data from our analysis suggest that SARS-CoV-2 infection in patients with pre-existing CD is not associated with an increased risk of hospitalisation or mortality. Additional studies are required to overcome the restrictions of the limited data available at present.

NMR-Based Metabolomics to Evaluate Individual Response to Treatments.

The aim of this chapter is to highlight the various aspects of metabolomics in relation to health and diseases, starting from the definition of metabolic space and of how individuals tend to maintain their own position in this space. Physio-pathological stimuli may cause individuals to lose their position and then regain it, or move irreversibly to other positions. By way of examples, mostly selected from our own work using 1H NMR on biological fluids, we describe the effects on the individual metabolomic fingerprint of mild external interventions, such as diet or probiotic administration. Then we move to pathologies (such as celiac disease, various types of cancer, viral infections, and other diseases), each characterized by a well-defined metabolomic fingerprint. We describe the effects of drugs on the disease fingerprint and on its reversal to a healthy metabolomic status. Drug toxicity can be also monitored by metabolomics. We also show how the individual metabolomic fingerprint at the onset of a disease may discriminate responders from non-responders to a given drug, or how it may be prognostic of e.g., cancer recurrence after many years. In parallel with fingerprinting, profiling (i.e., the identification and quantification of many metabolites and, in the case of selected biofluids, of the lipoprotein components that contribute to the 1H NMR spectral features) can provide hints on the metabolic pathways that are altered by a disease and assess their restoration after treatment.

Anxiety and Associated Factors during the COVID-19 Pandemic Confinement in the Moroccan Adult Celiac Disease Population

Introduction: The widespread lockdown due to the COVID-19 pandemic was insured by Moroccan authorities in early 2020 to preserve the health of citizens. The lockdown and the pandemic imposed psychological effects on the population including anxiety. Celiac disease (CeD), a chronic disease among the most common inflammatory intestinal disorders, has been linked to adult emotional disturbances. Hence, CeD patients may suffer from anxiety or increase this condition due to the concomitant situation. The objective of this study was to assess COVID-19-related anxiety in a sample of adults with CeD in comparison with a matched healthy group. Method(s): CeD patients (103) and matched healthy group (101) were investigated using a web-based COVID-19 and related lockdown anxiety survey. Anxiety was assessed with the State and Trait Anxiety Inventory (STAI test: Y1 for state anxiety and Y2 for trait anxiety). Result(s): State anxiety was present among 65.3% of CeD and 41.6% of the comparison group, and the difference was statistically significant. CeD women suffered more from state anxiety than their compeers in the comparison group (t = 3.23;p = 0.002), and a significant correlation between good compliance to GFD and less state anxiety was found among CeD patients (r = 0.31;p = 0.002). 61.8% of CeD participants thought they were at higher risk of contamination by COVID-19, and they were mostly women (chi2 = 7.66, p < 0.006) and had significantly higher state anxiety mean scores than their compatriots who did not express these thoughts (t = 2.93;p = 0.004). Additionally, 41.5% of CeD participants had anxiety as a trait against 26.7% in the comparison group and the difference between the two groups was statistically significant. Conclusion(s): Results of this survey allow a better understanding of the health-related pandemic effects on Moroccan CeD patients. It demonstrates that COVID-19 and related lockdowns had a serious impact on the psychological balance of these patients by increasing their anxiety. The survey results underlined the need to improve the psychological care of CeD patients notably by considering remote medical visits during this ongoing pandemic to provide mental health support. Copyright © 2023 The Author(s). Published by S. Karger AG, Basel on behalf of NOVA National School of Public Health.

Immune responses to SARS-CoV-2 vaccines in celiac disease.

BACKGROUND AND AIMS: SARS-CoV-2 infection and development of the disease COVID-19 is a serious threat to our society. Effective vaccines have now entered the market, but most patient populations were not included in the registration clinical trials. There is evidence that patients with celiac disease (CeD) have reduced effect of vaccines such as the hepatitis B vaccine. Hence, we investigated the humoral response to SARS-CoV-2 vaccines (Chadox1, Comirnaty and Spikevax) in CeD patients and healthy controls. METHODS: CeD patients from a patient registry at Oslo University Hospital were invited to donate serum samples before and after vaccination. We sent out 1537 invitations and received paired samples from 85 individuals. These were compared with similar samples from 238 healthy controls. Sera were analyzed for antibodies to the Spike protein from SARS-CoV2 and the receptor-binding domain. The results where then converted into binding antibody units (BAU)/ml to compare. RESULTS: Prevaccination samples showed that very few patients had been earlier exposed to Sars-CoV2 and the antibody levels were low. Postvaccination analysis showed overlap of antibody levels between CeD and healthy controls. On average, the CeD patient group had 5555.0 BAU/ml (330.1 SD) while the average in healthy controls was 5419 (184.7 SD). CONCLUSION: The humoral response to SARS-CoV-2 vaccines in CeD patients is similar to that observed in healthy controls.

Uptake of No- Biopsy Approach in Diagnosing Paediatric Coeliac Disease in a Regional Tertiary Centre

Background Coeliac disease (CD) is an immune mediated systemic disorder strongly associated with HLA DQ2 and DQ8 haplotypes.2 In 2012 The European Society for Paediatric Gastroenterology Hepatology and Nutrition (ESPGHAN) recommended serology based No-Biopsy Approach to the diagnosis of CD if I - Perifollicular Petechiae the following criteria are met1: Design/Methods A 6-year retrospective study of all children who attended coeliac clinic at The Great North Children Hospital, Newcastle. Data obtained using electronic patient records included TGA-IgA, EMA-IgA, symptoms at initial presentation and histopathological reports. HLA typing results were obtained from the Regional NHS blood and transplant laboratory. 346 children with CD were reviewed in the coeliac clinic from July 2013 to July 2019. Age range 0.9 - 16.5 years (median 9.5 years) and 54% female. Exclusion criteria include diagnosed outside study period or the UK, TGA-IgA at initial presentation unavailable for review. Results 66% of cases had TGA-IgA >=10xULN at initial presentation. 48% were diagnosed by serology based No-Biopsy Approach (figure1). Duodenal biopsies were performed in 82 cases. Biopsies were performed for type1 diabetes -8.5% and asymptomatic patients with first-degree relative with CD -8.5% (figure 1). EMA-IgA positivity was reported in 65/68 cases with symptoms attributed to CD in 62 cases in the cohort. A total of 13/62 cases had HLA risk alleles DQ2 and/or DQ8 performed (figure 2). Conclusion(s)*HLA screening uptake was 63%. The low uptake of HLA typing may have contributed to the increased number of cases undergoing duodenal biopsies.*Based on 2012 guidelines 19% of cases had duodenal biopsies for diagnosis of CD despite meeting the criteria for no biopsy approach.*Based on 2020 guidelines 96% of cases had duodenal biopsies for diagnosis of CD despite meeting the criteria for no biopsy approach.*The changes in the CD guidelines from 2012 to 2020 have resulted in an increase from 16% to 96% of cases that may have benefitted from no biopsy approach to the diagnosis of CD.*A unifying approach to the diagnosis of the CD will reduce the variability in investigations.*The current restrictions to Aerosol Generating Procedures due to SARS-CoV -2 pandemic will have a positive impact on establishing a No-Biopsy approach to the diagnosis of CD.

Ketoacidosis and age distribution in new-onset type 1 Diabetes during COVID-19 Pandemic

Background. There are numerous reports indicating increased risk of diabetic ketoacidosis (DKA) in new-onset type 1 diabetes (T1D) in childhood during COVID-19 pandemic. Delayed diagnosis, reduced access to immediate health care and psychological effects of pandemic have been suggested as possible reasons. Method(s): We conducted cross sectional, single-center study at Department of Pediatrics, University Hospital Center Zagreb, Croatia, evaluating severity of DKA in patients diagnosed during COVID-19 pandemic as compared to pre-pandemic period. Besides COVID-19 pandemic, Croatia suffered two severe earthquakes, adding psychological burden and difficulties to health care organization. The data collected for the period March 2012 - March 2022 included: age, sex, laboratory parameters at presentation (pH, HCO3, HbA1c), association of celiac and autoimmune thyroid disease and frequency of positive pancreatic antibodies. The pandemic group (PG) included patients diagnosed form March 2020 to March 2022 while previously diagnosed patients comprised control group (CG). Result(s): There were 107 patients in pandemic group (57M/50F) as compared to 337 controls (191M/146F). No significant difference was found between PG and CG regarding age (9.2/ 8.9 years), sex, DKA frequency (44.9/40.4%) or severity (mild: 15.2/13.8%;moderate 15.2/13.5%;severe: 13.3/12.3%), HbA1c at diagnosis (11.5/ 11.2%) and frequency of admission to intensive care unit. There was no difference regarding frequency of celiac (5.6/ 3.0%) and autoimmune thyroid disease (15.0/22.0%) at presentation, or negative pancreatic antibodies (6.8%/4.5%). We found significantly higher frequency of new-onset diabetes in children < 5 years during pandemic (32.7% vs. 20.5%, p=0.009). Particularly increased frequency during pandemic was noted in children < 2 years (12.1% vs. 6.2%, p=0.045). The age distribution was as following in PG/CG: <2 yrs 12.1/6.2%, 2-5 yrs 20.6/14.2%, 5-11 yrs 26.2/41.8%, 11-18 yrs 41.1/37.7%. No difference in DKA frequency or severity between PG and CG was noted among age groups. When comparing 1st and 2nd pandemic year, there was no difference regarding age, sex, frequency and severity of DKA. Conclusion(s): Despite adversities experienced during COVID- 19 pandemic and post-earthquake recovery, we did not find increased frequency or severity of DKA in new-diagnosed T1D. However, we found increased percentage of new-onset T1D among patients <5 years during pandemic, particularly < 2 years, but we did not find increased DKA presentation in any age group. Further studies are necessary to elucidate the effect of COVID-19 pandemic on presentation and related complications of T1D and to determine if the shift toward the younger age at presentation will be abiding.

Clinical and immunological characteristics of new-onset type 1 diabetes in children during the COVID-19 pandemic

Background. Type 1 Diabetes (T1D) is a chronic disease resulting from autoimmune destruction of insulin-secreting pancreatic beta cells. Viruses are known to play a role in the pathogenesis of T1D. There is no consistent evidence that SARS-CoV-2 induces T1D in children or adults. Nevertheless, evidence suggests that the SARSCoV- 2 affects beta cell function, suggesting a role for the virus in the pathogenesis of the disease. It is thus plausible that the effects of the SARS-CoV-2 on beta cells and the environmental alterations caused by the COVID-19 pandemic affected the clinical and immunological characteristics of new-onset T1D. Objective(s): To find the clinical and immunological signatures of the COVID-19 pandemic on children diagnosed with T1D. Method(s): A single-center, retrospective observational study comparing the clinical and immunological characteristics of children diagnosed with T1D at our clinic the year before and during the first two years of the COVID-19 pandemic. Data were extracted from the medical records of the children at the time of diabetes diagnosis, including clinical and demographic parameters, COVID-19 PCR results, and the presence of anti-islet, thyroid, and celiac-related autoantibodies. Also obtained from the medical records were a family history of T1D, celiac disease, and autoimmune thyroid disease in a first-degree family member. Result(s): 376 children were diagnosed with T1D at our diabetes clinic during the study period. 132, 121, and 123 children were diagnosed during the pre-COVID-19 era, the first and second pandemic years, respectively. The rate of diabetic ketoacidosis at presentation was slightly higher during the COVID-19 era than in the pre-COVID-19 era (not reaching statistical significance) and comparable between the first and second pandemic years. Multiple antibodies were significantly higher among patients diagnosed in the pre-COVID-19 era than those diagnosed in the first two years of the pandemic (72% vs.61%, p=0.03). Islet-cell autoantibodies (ICA) levels were higher among children diagnosed during the COVID-19 era compared to pre-COVID-19 era (1341.34+1786.36U/ml vs.968.02+1495.66U/ml, p=0.042). GADantibodies levels were higher in children diagnosed with COVID- 19 before the diagnosis of T1D than in children without COVID-19 (614.86+793.90U/ml vs.317.08+611.45U/ml, p=0.027). Tissue Transglutaminase antibodies were more common among children diagnosed during the COVID-19 era compared to the pre- COVID-19 era (17% vs. 8%, p=0.024). Conclusion(s): Our findings suggest that SARS-CoV-2 and the environmental alterations caused by the pandemic affected the immunological profile of children diagnosed with T1D. Thus, it appears that the virus plays a role in the autoimmune process causing T1D.