A Case of X-Linked Moesin-Associated Immune Deficiency in a Pediatric Patient

Background: X-Linked Moesin-Associated Immune Deficiency (X-MAID) is a rare severe combined immunodeficiency (SCID) subtype that can present at any age due to its variability. Depending on severity, patients demonstrate failure to thrive, recurrent bacterial and viral infections, and increased susceptibility to varicella zoster. It has been characterized by marked lymphopenia with hypogammaglobulinemia and impaired T-cell migration and proliferation. Case Presentation: This is a report of a Cuban 7-year-old male with poor weight gain and facial dysmorphia. He had a history of recurrent bacterial gastrointestinal infections and pneumonia beginning at 4 months of age. He additionally had 4-6 upper respiratory tract and ear infections annually. While still living in Cuba, he was admitted for a profound EBV infection in the setting of significant leukopenia. A bone marrow biopsy confirmed no malignancy. After he moved to the United States, his laboratory work-up revealed marked leukopenia with low absolute neutrophil and lymphocyte count with low T and B cells, very low immunoglobulin levels IgG, IgA, and IgM, and poor vaccination responses to streptococcus pneumonia, varicella zoster, and SARS-CoV-2. Genetic testing revealed a missense pathogenic variant c.511C>T (p.Arg171Trp) in the moesin (MSN) gene associated with X-MAID. He was managed with Bactrim and acyclovir prophylaxis, and immunoglobulin replacement therapy, and considered for hematopoietic stem cell transplantation. Discussion(s): Diagnosis of X-MAID should be considered in patients with recurrent infections and profound lymphopenia. As with SCID, early diagnosis and intervention is of utmost importance to prevent morbidity and mortality. This case demonstrates the importance of genetic testing in identifying this disease as it may prompt an immunologist to consider HSCT if conservative management is suboptimal. In the current literature, HSCT appears promising, but the long-term outcomes have yet to be described.Copyright © 2023 Elsevier Inc.

Child, adolescent, and parent mental health in general population during a year of COVID-19 pandemic in belgium: a cross-sectional study

Background: This study aims to evaluate the mental health status of children, adolescents and their parents during the first year of COVID-19 pandemic in Belgium. Method(s): Analysis compared results before and during the second national lockdown, which started on November 2nd 2020. A cross-sectional online survey was conducted between May 2020 and April 2021. Result(s): Two hundred and eighteen adults and 273 children fully completed the survey. Almost one in five children (17.9%) presented moderate-to-severe scores of depression. Adolescents presented a higher level of depression than children (p = 0.007). The rate of moderate-to-severe depression scores (10.8% to 21%, p = 0.007) and internalized symptoms increased during the second lockdown (p < 0.001). Parents' depression (p < 0.001) and anxiety (p = 0.027) levels also increased during the second lockdown. Logistic regression showed that the use of psychotropic medication in parents and parents' depression scores were risk factors for children to have worse depression scores. Conclusion(s): The second lockdown appears to worsen the effects of the pandemic on children's and parents' mental health. There is a need to implement specific interventions targeting both children/adolescents and their parents to support them during lockdown periods and improve mental health outcomes.Copyright © 2022, The Author(s).

IRF2BP2 mutation with autoimmune enteropathy, immune deficiency, and respiratory failure

Case history: We present the case of a 31-year-old Hispanic male with history of recurrent bronchiectasis, invasive aspergillosis, and severe persistent asthma, who is now status post lung transplant for end-stage lung disease. He initially presented at 7 years of age with diarrhea, failure to thrive, and nearly absent immunoglobulin levels (IgG < 33 mg/dL, IgA < 7 mg/dL, IgM = 11 mg/dL, IgE = 4 IU/dL) necessitating IVIG treatment. Small intestinal biopsy showed villous atrophy consistent with autoimmune enteropathy. Sweat chloride was reported as indeterminate (44 me/dL). Initial WBC, platelet, and T- and NK-cell counts were within normal range, and B-cell count and percentage were borderline low. Most recently, he was found to have increased immature B-cell count (CD21low), decreased memory B-cells, and poor pneumococcal vaccine antibody response. Patient has been hospitalized numerous times with increasingly severe bronchiectasis, pneumonitis, and COVID-19 infections twice despite vaccination, leading to respiratory failure and lung transplantation. Family history is negative for immune deficiency and lung diseases. Discussion(s): Of these 3 VUSs (see the table), the one in IRF2BP2 has the most pathogenic potential due to its autosomal dominant inheritance, its location in a conserved domain (Ring), and previous case reports of pathogenic variants at the same or adjacent alleles 1-3. Baxter et al reported a de novo truncating mutation in IRF2BP2 at codon 536 (c.1606CinsTTT), which is similar to our patient's mutation. This patient was noted to have an IPEX-like presentation, with chronic diarrhea, hypogammaglobulinemia, and recurrent infections. Variant Functional Prediction Score for our variant predicts a potentially high damage effect. There are 2 other case reports of heterozygous mutations in loci adjacent to this allele;one (c.1652G>A)2 with a similar clinical phenotype to our patient and the other (C.625-665 del)3 with primarily inflammatory features and few infections. Impact: This case highlights a variant in IRF2BP2 associated with severe hypogammaglobulinemia, recurrent pulmonary infections, and autoimmune enteropathy. [Table presented]Copyright © 2023 Elsevier Inc.

Mild COVID-19 clinical course among paediatric patients with primary immunodeficiency

Background: The clinical course of coronavirus disease-2019 (COVID-19) varies from those who are asymptomatic, experience mild symptoms such as fever, cough, and dyspnea, to more severe outcomes including acute respiratory distress, pneumonia, renal failure, and death. Early reports suggested severe outcomes in patients with primary immunodeficiency (PID), particularly those with type 1 interferon signalling defects. This prompted a rigid approach to social distancing to protect this patient population, particularly children. To date, real-world data describing the course and outcome of COVID-19 in paediatric PID patients remains scarce. Method(s): In this retrospective case series, we describe the clinical course of 36 paediatric patients with underlying primary immunodeficiency (PID) followed by SickKids Hospital (Toronto, Canada) who were symptomatic and tested positive for SARS-CoV-2 infection between October 2020 to November 2022. Result(s): Our cohort consisted of patients with combined immunodeficiency (66.7%), antibody deficiency (22.2%), neutrophil dysfunction (8.3%), and immune dysregulation (2.8%). The median age was 7.5 years (range: 8 months - 17 years), with 21 male and 15 female patients. Three (8.3%) patients were post-hematopoietic stem cell transplant (HSCT) and 12 (33%) patients were on immunoglobulin replacement. Nine (25%) patients had underlying lung problems including bronchiectasis (1), interstitial lung disease on home oxygen therapy (1), and underlying asthma (7). Most patients had mild clinical course and were managed at home. The most common symptoms were fever (80%), cough (75%) and other upper respiratory tract symptoms (72%). Nineteen (52.7%) patients experienced other symptoms which included headache, lethargy, or gastrointestinal upset. At the time of the infection, 13 patients (36.1%) had received 2 doses of a SARS-CoV-2 vaccine, 5 patients (13.9%) had received 1 dose, and 18 (50%) were not vaccinated. None of the patients received antiviral or monoclonal antibody as prophylaxis or treatment. Only 1 patient required hospital admission out of precaution given the close proximity to HSCT. All patients recovered without complications. Conclusion(s): The paediatric patients with PID followed by our centre experienced mild to moderate COVID-19 symptoms and recovered fully without complications. These findings support the return of much needed social interactions among children, which were impacted severely during the COVID-19 pandemic.Copyright © 2023 Elsevier Inc.

Comprehensive Code List Associated with CDC-Defined High-Risk Underlying Medical Conditions Leading to Potential Progression to Severe COVID-19 Outcomes

Objectives: This analysis was conducted to develop a comprehensive list of ICD-10 CM codes for underlying conditions identified by the CDC as being associated with high-risk of developing severe COVID-19 and assessed the consistency of these codes when applied to large US based datasets. Method(s): The comprehensive list of ICD 10-CM codes for CDC-defined high-risk underlying conditions were mapped from CDC references and FDA Sentinel code lists. These codes were subsequently applied to Optum's de-identified Clinformatics Data Mart Database (claims) and the Optum de-identified Electronic Health Record (EHR) database across 3 years (2018, 2019 and 2020) among continuously enrolled subjects >= 12 years of age to determine the performance and consistency in identifying these high-risk underlying conditions annually over these years. Result(s): A total of 10,276 ICD-10 codes were mapped to 21 underlying conditions. Within the claims data, 62.7% of subjects >= 12 years had >= 1 CDC-defined high-risk condition (excluding age) with 26.6% of patients >= 65 years while in the EHR data 38% had >= 1 high-risk underlying condition (excluding age) with 14.4% >= 65 years. These results were similar and consistent in both datasets across all years. Patients aged 12-64 years in the claims data had a higher rate of >=1 high risk underlying condition relative to the EHR data, 49.3% and 34%, respectively. The top 5 conditions among the >= 65 were identical across both databases: hypertension, immunocompromised status, heart conditions, diabetes (type 1 or 2), and overweight/obesity. The top 5 conditions among the 12-64 age group were also similar among the databases and included: immunocompromised status, hypertension, overweight/obesity, smoking (current or former), and mental health conditions. Conclusion(s): These findings present a comprehensive list of codes that can be used by researchers, clinicians and policy makers to identify and characterize patients that may be at high-risk for severe COVID-19 outcomes.Copyright © 2023

Dynamic modelling of changes in emotional and behavioural problems in children and adolescents during the COVID-19 pandemic

Aims: Children and adolescents were affected in various ways by the measures due to COVID-19 pandemic. The aims of this study were to investigate and compare the effects on mental health across age, to identify latent class trajectories of emotional and behavioural problems over 12-months and to examine the association of classes of trajectories with baseline demographic and clinical predictors. Method(s): Children (n = 1854) and adolescents (n = 1243) from the general population were assessed baseline, at 6-, 9-, and 12-month follow-up. They were eligible if they were residents in Austria, Germany, or Switzerland, were parents/caregivers of a child aged between 7 and 10 years or adolescents >=11 years, had sufficient German language skills and provided informed consent. Results and Conclusion(s): Significant age-effects were found regarding type and frequency of problems. While children had the largest increase in aggressive behaviours, adolescents reported the largest increase in emotional problems. Sociodemographic variables, exposure to and appraisal of COVID-19, psychotherapy before COVID-19 and parental mental health significantly predicted change in problemscores (F >= 3.69, p <= .001). Using growth mixture modelling, a oneclass solution was detected for the trajectory of aggressive behaviours and a two- and three-class solution for withdrawn/depression and anxiety/depression. A substantial proportion of children and adolescents experienced age-related mental health problems during the different stages of the COVID-19 pandemic. These results suggest that psychological problems of specific sub-groups should be monitored over the longer-term and interventions to improve communication, emotion regulation, and appraisal style should be offered to risk groups.

Comparison of Comorbidities between Adults and Children with Glycogen Storage Disease Type Ia (GSDIA)

Objectives: Glycogen Storage Disease Type Ia (GSDIa) is a rare inherited disorder resulting in acute hypoglycemia due to impaired release of glucose from glycogen. Despite dietary management practices to prevent hypoglycemia in patients with GSDIa, complications still occur in children and throughout adulthood. This retrospective cohort study compared the prevalence of complications in adults and children with GSDIa. Method(s): Using ICD-10 diagnosis codes, the IQVIA Pharmetrics Plus database was searched for patients with >=2 GSDI claims (E74.01) from January 2016 through February 2020, with >=12 months continuous enrollment beginning prior to March 2019 (for one year of follow-up before COVID-19), and no inflammatory bowel disease diagnoses (indicative of GSDIb). Complication prevalence in adults and children with GSDIa was summarized descriptively. Result(s): In total, 557 patients with GSDIa were identified (adults, 67%;male, 63%), including 372 adults (median age, 41 years) and 185 children (median age, 7 years). Complications occurring only in adults were atherosclerotic heart disease (8.6%), pulmonary hypertension (3.0%), primary liver cancer (1.9%), dialysis (0.8%), and focal segmental glomerulosclerosis (0.3%). Other complications with the greatest prevalence in adults/children included gout (11.8%/0.5%), insomnia (10.0%/1.1%), osteoarthritis (22.0%/2.7%), severe chronic kidney disease (4.3%/0.5%), malignant neoplasm (10.8%/1.6%), hypertension (49.7%/8.7%), acute kidney failure (15.3%/2.7%), pancreatitis (3.0%/0.5%), gallstones (7.8%/1.6%), benign neoplasm (37.4%/8.1%), hepatocellular adenoma (7.0%/1.6%), neoplasm (41.1%/9.7%), and hyperlipidemia (45.2%/10.8%). Complications with the greatest prevalence in children/adults included poor growth (22.2%/1.9%), gastrostomy (29.7%/3.2%), kidney hypertrophy (2.7%/0.8%), seizure (1.6%/0.5%), hypoglycemia (27.0%/11.3%), hepatomegaly (28.7%/15.9%), kidney transplant (1.6%/1.1%), diarrhea (26.5%/18.6%), nausea and/or vomiting (43.8%/35.8%), acidosis (20.0%/17.2%), and anemia due to enzyme disorders (43.8%/40.6%). Conclusion(s): GSDIa is associated with numerous, potentially serious complications. Compared with children, adults with GSDIa had a greater prevalence of chronic complications, potentially indicating the progressive nature of disease. Children with GSDIa had more acute complications related to suboptimal metabolic control.Copyright © 2023

Recurrence of multisystem inflammatory syndrome associated with Covid-19 infection: case report.

The COVID-19 pandemic has left millions of cases and deaths worldwide, in children the infection is less severe and has low mortality. A post-infectious entity called Systemic Multiinflammatory Syndrome (MIS-C) associated with COVID-19 infection is described, which has a mortality rate ten times higher than acute infection in children. MIS-C is characterized by sustained systemic inflammatory manifestations associated with fever and multiple system involvement. We present the case of a schoolgirl who presented a diagnosis of MIS-C with a good response to management and 11 months later, she presented a second episode that also responded to treatment. To date, we have not found in the literature the report of recurrence of MIS-C in children, such as the case presented by us, it marks an important precedent, inviting us to consider recurrence as a possibility in the case of a similar clinical presentation.Copyright © 2023 Asociacion Colombiana de Infectologia. All rights reserved.

Multisystem Inflammatory Syndrome in Children: Characteristics and Epidemiology

Shortly after the novel coronavirus (now known as SARSCoV- 2) was recognized, data began to accumulate on the virus's effects on children. Initial data showed that children were more likely to be mildly affected, compared to adults, with lower risks of hospitalization and death. However, in April of 2020, reports appeared of a severe disease in children occurring about two-six weeks after infection with SARS-CoV-2. The features were similar to those seen in a rare vasculitis condition called Kawasaki disease. On May 14, 2020, the Centers for Disease Control and Prevention (CDC) issued a national health advisory regarding this new condition, which was called multisystem inflammatory syndrome in children (MIS-C). The current case definition for MIS-C includes six criteria: (1) serious illness leading to hospitalization or resulting in death;(2) age less than 21 years;(3) measured fever over 38 degrees Celsius or report of subjective fever;(4) laboratory evidence of inflammation;(5) new onset involvement in at least two of the following (cardiac involvement, mucocutaneous involvement, shock, gastrointestinal involvement, and hematologic involvement);and (6) laboratory-confirmed SARS-CoV-2 infection or an epidemiologic link to a person with COVID-19. According to CDC, as of January 3, 2023, there have been 9,333 patients in the United States meeting the case definition of MIS-C, with 76 deaths. The median age of patients was nine years, with half of those affected between the ages of five and 13 years. More than half of the reported patients on whom race-ethnicity information was available were in children who are Hispanic/Latino or Black, non-Hispanic. Over 60% of reported patients were male. Most affected children had previously been healthy. A better understanding of the pathogenesis of this serious illness is needed to provide better treatment options for children with MIS-C. Prevention of MIS-C is focused on the prevention of SARS-CoV-2 infection through staying up to date with COVID-19 vaccination, masking, and other prevention strategies.

COVID-19-Related Encephalitis in a Child with PIK3CD Defect

Introduction: COVID-19 related encephalitis has been reported in pediatric patients;however, there are no reports in patients with inborn errors of immunity (IEI). Activated PI3K Delta Syndrome (APDS) is a disease of immune dysregulation with immunodeficiency, autoimmunity, and abnormal lymphoproliferation resulting from autosomal dominant gain-offunction variants in PIK3CD or PIK3R1 genes. We investigate a family with APDS, one mother and three children, one of whom developed COVID-19 related encephalitis. Method(s): Patients were consented to an IRB-approved protocol at our institution. Medical records and detailed immunophenotyping were reviewed. Family members were sequenced for IEI with a targeted gene panel. Result(s): The index case is a 10-year-old female with a known pathogenic variant in PIK3CD (c.3061 G > A, p.Glu1021Lys), who contracted SARS-COV-2 despite one COVID-19 vaccination in the series. Her disease course included COVID-related encephalitis with cerebellitis and compression of the pons, resulting in lasting truncal ataxia and cerebellar mutism. At that time, the patient was not on immunoglobulin replacement therapy (IgRT), but was receiving Sirolimus. Besides the index case, 3 family members (2 brothers, 1 mother) also share the same PIK3CD variant with variable clinical and immunological phenotypes. All children exhibited high transitional B-cells, consistent with developmental block to follicular B cell stage. Increased non-class switched IgM+ memory B cells and skewing towards CD21lo B cell subset, which is considered autoreactive-like, was observed in all patients. Of note, the patient had low plasmablasts, but normal immunoglobulins. Of her family members, only one was receiving both sirolimus and IgRT. Conclusion(s): We describe a rare case of COVID-19-related encephalitis in a patient with inborn error of immunity while not on IgRT. This may indicate infection susceptibility because of a lack of sufficient immunity to SARS-CoV-2, unlike the rest of her family with the same PIK3CD variant.Copyright © 2023 Elsevier Inc.

Cardiac manifestations of post-COVID syndrome in children and adolescents.

The aim of the research. To study the features of cardiovascular system disorders in post-covid syndrome (PCS) in children and adolescents after a mild form of coronavirus infection (COVID-19). Material and methods. From 260 children and adolescents after a mild form of COVID-19, a total of 30 patients aged 7-17 years with cardiac manifestations of PCS were selected. Therewith, 32 patients with an uncomplicated form of the disease were selected to form a comparison group. In 3 and 6 months after disease onset, a comprehensive examination of patients was performed with a questionnaire on the subjective scale for MFI-20 assessment asthenia (Multidimensional Fatigue Inventory-20), electrocardiography (ECG), echocardiography;daily monitoring of ECG and blood pressure. The biochemical blood test included assay of creatine phosphokinase-MB (CPK-MB), troponin I and lactate dehydrogenase (LDH). Results. The incidence of PCS with cardiac manifestations amounted to 11.5 %. After 3 months from the disease onset, complaints of pain and discomfort in the chest, palpitations, fatigue, and poor exercise tolerance persisted. Asthenic syndrome was diagnosed in 70 % of patients. The "general asthenia" indicator totalled14 [12;16] points (p<0.001) and was associated with the age of patients (r=+0.5;p<0.05). Arrhythmic syndrome and conduction disorders were detected in 67% of children. Labile arterial hypertension and hypotension occurred in 23 % of the adolescents. The increase in CPK-MB remained in 17% of the children, LDH - in 10%. In the sixth month after the onset of the disease, there were no significant differences in the results of the examination in the observation groups. However, a decrease in the level of resistance within 6 months was recorded in 43.3% of the schoolchildren with PCS (p<0.001). Conclusion. The data obtained indicate the need for early verification of cardiopathies in children with COVID-19, determination of a set of therapeutic and rehabilitation measures as well as ECG monitoring.Copyright © 2022, Krasnoyarsk State Medical University. All rights reserved.

Anti-SARS-CoV-2 antibodies important in diagnostics of acute hepatitis in children

The most common causes of acute hepatitis in children are hepatitis A and autoimmune hepatitis. Hepatitis in the course of Wilson's disease is sporadically registered in adolescents. An increase of activity of aminotransferases both in the course of multisystem inflammatory syndrome in children (MIS-C) and in the course of COVID-19 has been observed. Hepatitis is common in children with MIS-C and is associated with a more severe presentation and persistent elevation of liver function tests. To date, no cases of acute hepatitis in children due to COVID-19 have been reported. We present 2 cases of acute hepatitis in children where the only cause seems to be a previous asymptomatic SARS-CoV-2 infection.Copyright © 2023 Termedia Publishing House Ltd.. All rights reserved.

EBV-related lymphoproliferative disease in Wiskott-Aldrich Syndrome patient

Case: Wiskott-Aldrich Syndrome (WAS) is a rare X-linked inborn error of immunity caused by mutations in the WAS gene. It is classically characterized by immunodeficiency, eczema, and micro-thrombocytopenia. It has been known since the 1960s that patients with WAS have an increased risk of lymphoproliferative disease though the exact incidence remains unknown in the American population. Limited case reports have discussed EBV-related lymphoproliferative disease in patients with WAS. We present a case of a 9-year-old boy with known WAS complicated by eczematous rash, thrombocytopenia, recurrent ear infections, and monoclonal gammopathy who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. Family had been offered treatment with hematopoietic stem cell transplant but declined multiple times in the past. Earlier in the year, he presented with possible MIS-C with negative SARS-CoV-2 PCR. He presented to our hospital with mastoiditis and lymphadenopathy. Physical examination showed severe eczema on hands and tender right mastoid. Laboratory evaluation showed thrombocytopenia, elevated IgG of 6290, IgA of 744, IgE of 827, low IgM of 41, and 14% response to pneumococcal titers. He was empirically treated with intravenous antibiotics. ENT performed right postauricular incision and drainage and the culture grew Hemophilus influenza. Throughout his hospital stay, his submandibular lymphadenopathy became more prominent despite treatment. Core needle biopsy of right submandibular lymph node was suggestive of EBV-associated lymphoid hyperplasia. EBV PCR and antibodies were both positive. CT chest, abdomen, and pelvis revealed multifocal pulmonary lymphadenopathy and a diffuse, bilateral nodularity as well as retroperitoneal and mesenteric lymphadenopathy. He was given four doses of weekly Rituximab, which successfully decreased EBV viremia below linear detectability. Immunoglobulin replacement therapy (IgRT) was initiated. Bronchoalveolar lavage and lung biopsy were performed and are results are currently pending. Discussion(s): We present a case of a 9-year-old boy with known WAS awaiting transplant who was found to have submandibular EBV-associated lymphoid hyperplasia with associated lung and retroperitoneal lymphadenopathy. While lymphoproliferative disease is a known complication of WAS, EBV-related lymphoproliferative disease in WAS patients has only been reported as case reports and remains a rare but known complication of patient with WAS.Copyright © 2023 Elsevier Inc.

COVID-19 Vaccination Hesitancy Among 5-11-year-old Iranian Children's Parents: What Are Underlying Beliefs?

Background: Of all teenage deaths caused by coronavirus disease 2019 (COVID-19), 47% occurred in children aged 0-9. Like many other infectious diseases, reducing mortality in children requires widespread vaccination. Despite the availability of the COVID-19 vaccine, a large percentage of children have not received the vaccine. Objective(s): This survey aimed to study parents' reluctance to receive the COVID-19 vaccine for their children in Shiraz, Iran. Method(s): An online questionnaire was sent to parents whose 5 to 11-year-old children had received no COVID-9 vaccine through the health educators of primary schools in Shiraz, Iran. The questionnaire contained demographic questions and 16 beliefs about COVID-19 vaccination that were answered as yes/no. Result(s): We assessed 1093 respondents, including 49.5% (n = 542) male and 50.5% female students' parents. The mean number of wrong beliefs was 7.21 +/- 2.80 in parents who had boys and 7.78 +/- 2.95 in girls' parents. Also, 78.6% of participants had at least five wrong beliefs or excuses for not vaccinating their children. Notably, 82.8% of mothers and 84.3% of fathers were vaccinated with 2-3 doses against COVID-19. The most common wrong beliefs were probable vaccines' side effects in the future, the undesirable effect of vaccination on children's growth, and the awful effect of the vaccine on fertility, with a prevalence of 82.7%, 81.2%, and 76.7%, respectively. Conclusion(s): This study identified that most participants believed that COVID-19 vaccines have side effects for their children and unfavorable effects on children's growth and infertility.Copyright © 2023, Author(s).

Report of the Association Between Multisystem Inflammatory Syndrome and Severe Myocarditis

Introduction: The people worldwide have been affected by severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection since its appearance in December, 2019. Kawasaki disease-like hyperinflammatory shock associated with SARS-CoV-2 infection in previously healthy children has been reported in the literature, which is now referred to as a multisystem inflammatory syndrome in children (MIS-C). Some aspects of MIS-C are similar to those of Kawasaki disease, toxic shock syndrome, secondary hemophagocytic syndrome, and macrophage activation syndrome. Case Presentation: This study reported an 11-year-old boy with MIS-C presented with periorbital and peripheral edema, abdominal pain, elevated liver enzymes, severe right pleural effusion, moderate ascites, and severe failure of right and left ventricles. Conclusion(s): Due to the increasing number of reported cases of critically ill patients afflicted with MIS-C and its life-threatening complications, it was recommended that further studies should be carried out in order to provide screening tests for myocardial dysfunction. Adopting a multidisciplinary approach was found inevitable.Copyright © 2023, Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/) which permits copy and redistribute the material just in noncommercial usages, provided the original work is properly cited.

The Evolution of the Covid-19 Pandemic in Pediatric Patients with Sickle Cell Disease: From Alpha to Omicron

Background: Approximately two years ago, COVID-19 was declared a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and through genomic surveillance, we have seen the emergence of variants of SARS-CoV-2. In the United States, over 78 million cases and >900,000 deaths attributable to COVID-19 have been reported. SCD was identified as a risk factor for severe COVID-19 disease in adults and pediatric patients. The emergence of novel SARs- CoV-2 variants has led to challenges in diagnosis, treatment, and prediction of long-term sequelae in individuals with SCD and COVID-19. Aim(s): We compare the overall seasonal variation of COVID-19 variants and patterns of healthcare utilization and clinical presentation over time in pediatric patients with SCD and COVID-19 at Children's National Hospital (CNH). Method(s): Our single-center, observational cohort study included 193 pediatric patients with SCD (0-21 years) with PCR-confirmed SARSCoV- 2 infection between March 31, 2020, and January 31, 2022. Per the SECURE SCD Registry definitions, clinical severity was classified as asymptomatic, mild, moderate, and severe. Result(s): A total of 193 unique patients with SCD and positive SARS-CoV-2 PCRs between March 2020-January 2022 were included in our registry. Most patients were female (51.8%), and the mean age was 11.2 years (SD 6.5 years). Most of the cohort resides in Maryland (N=135), and HbSS was the dominant genotype (69.4%). During the alpha dominant variant of the COVID-19 pandemic (March 2020- June 2021) there were 70 cases, followed by 40 cases during the Delta variant (July 2021- December 19, 2021), and 83 cases during the Omicron variant dominance (from December 20, 2021-January 31,2022). There were 149 patients (77%) that presented to the emergency department (ED) or were hospitalized. There were a total of 80 hospitalizations (41.5%), and a relative comparison showed that the percentage of hospitalizations was highest during the delta wave (47.5%) and lowest during the omicron wave (36.1%) (p= 0.407). ED-only utilization was highest in the era of omicron (43.4%, N=36), followed by delta (32.5%, N=13), and then alpha (30%, N=21)(p=0.197). The most common SCD-related complication was vaso-occlusive (VOC) pain (33%, N=64) which accounted for half of all hospital admissions (51%, N=41 of 80). Acute chest syndrome (ACS) was reported in 40% (N=32) of admitted patients and was highest in the alpha era (54.8%, N=17). The use of blood transfusion therapy was highest in the alpha (N=17) and delta (N=14) variants, while Remdesivir use was highest in omicron (N=15). A total of 6 patients received monoclonal antibodies (Delta, N=4;omicron, N=2). Throughout all the variants, there was a significant difference in COVID-19 clinical severity (p>0.005). Of the patients classified as asymptomatic (13%, N=25), seventy-two percent (n=18) were diagnosed during the alpha variant. Mild severity was the most prevalent (69%, N=134), with the omicron variant having the highest cases (51.5%, N=69). Severe cases were observed in all variants (6.7%, N=13) but were most prevalent during the alpha variant (46.2%, N=6). Summary - Conclusion(s): Interestingly, while the relative percentage of hospitalizations was lowest during the omicron wave, it saw the highest percentages of ER utilization. Overall, COVID-19 remains mild in pediatric patients with SCD, and notably, there was higher health care utilization in the omicron era.

Severe juvenile dermatomyositis with specific liver involvement onset concomitant with COVID-19 infection: A case report

Juvenile Dermatomyositis (JDM) is an autoimmune disease that involves skin, muscle and internal organ disorders. Its mechanisms still not well established, but the triggering role of viral infections has been described. In this context, the effect of the COVID-19 on the onset of autoimmune disorders such as JDM remains a matter of study and research. We report a severe JDM, following a confirmed COVID-19 infection in a previously healthy 8 year-old boy who presented with various skin lesions and a cholestatic liver involvement. Laboratory findings were consistent with an inflammatory myositis and an autoimmune liver disease. Skin and muscle biopsies confirmed the diagnosis of JDM. The therapy choice was difficult. Finally, he received a second line therapy of the JDM with a favorable outcome. The liver fragment analysis showed a steatosis. This case supports the hypothesis of COVID-19 triggering role in the genesis of JDM and autoimmune diseases.Copyright © 2023 Scientific Publishers of India. All rights reserved.

Health-related quality of life, mental health and caregiver burden in children with autosomal recessive polycystic kidney disease (ARPKD)

Objective: To examine whether established patient-reported outcome measures are suitable for capturing the impact of ARPKD in children and their families. Method(s): We assessed 44 children with ARPKD (40 families) with respect to patients' health-related quality of life ((hr- QOL) using PedsQLTM ESRD module) and mental health (strength and difficulties questionnaire (SDQ)) as well as family and caregiver burden (Impact on family score (IFS) und Ulm inventory of parental caregiver QOL (ULQIE)) and compared them to published data and 36 healthy control children matched for age and time. Result(s): Patients were aged 9.5 +/- 5.9 years (vs. controls 8.8 +/- 5.0, p = ns) and 21 (48%) were female (vs. 19 controls (53%), p = ns). Mean eGFR was 81 ml/min*1.73m2 (range 4 - 165);7 received dialysis and 11 had functioning kidney transplants (KTX, 2 combined with liver transplants). Eight patients had developmental delay secondary to medical complications, while chronic illness was an exclusion criterion for healthy controls. 61 caregivers of affected children had same gender-distribution (61% vs. 60% mothers) and age (both 42 +/- 7 years) and number of dependent children (1.8 +/- 0.9 vs. 2.0 +/- 0.8) as 57 caregivers of healthy children. The mean proxy reported PedsQL Total score was 77.5 +/- 10.6 (range 59 - 96). It correlated significantly to eGFR (r = 0.5, p < 0.01, (also within the subpopulations pre- and post-KTX)). Parents reported greater mental health problems in affected than in control children with a higher SDQ total score mainly due to higher scores in the hyperactivity and peerinteraction subscales. ULQIE revealed that parents of affected children had significantly lower levels of physical functioning, self-fulfillment and general QOL, but despite higher emotional burden scores they indicated similar satisfaction with family life. Impact on family scores were in a similar range to those of children with moderate to severe disabilities. Conclusion(s): The good spread of PedsQLTM ESRD-scores and their correlation to renal function indicates that it captures significant aspects of ARPKD, however, it may need further adjustment to include liver complications. All four chosen instruments revealed significant impact of ARPKD on hrQOL and mental health of affected children as well as family life and parental wellbeing in comparison to healthy controls. More problems with peer-interactions may also be due to more stringent shielding of chronically ill children from social contacts during the COVID pandemic compared to healthy children.

Trends in Second Generation Antipsychotic Prescribing for Adolescents from 2013-2021

Objectives: To examine temporal trends of FDA-approved and off-label second-generation antipsychotic (SGA) prescribing for adolescents over time through the Covid-19 pandemic. Method(s): This is a new-user, retrospective longitudinal panel study using electronic health record data from a large, integrated health care system. Outpatient prescription orders for a new SGA (index date) for adolescents (age 10-17 years) during 2013-2021 were analyzed. Prescription orders were linked to diagnoses at time of encounter to examine prescribing behavior. A one-year lookback period was used for baseline inclusion and exclusion criteria, including one-year "washout" of SGAs and continuous insurance enrollment. FDA-approved use was determined by two outpatient diagnoses (one baseline diagnosis and the prescription order diagnosis) for autism, psychotic disorders, bipolar disorders, or Tourette's;the remaining proportion was considered potentially off-label. We report crude annual prescribing rates per 1,000 youths. Result(s): There were 8,145 unique patients with new SGA prescription orders, of which 5,828 (71.6%) had linked diagnoses available. Calendar year 2013 had the highest prescribing rate prior to Covid-19 onset (2.1 per 1,000) but then declined through 2016 (1.7 per 1,000). Prescribing rates in 2020 (2.0 per 1,000) and 2021 (2.2 per 1,000) were higher than those between 2017-2019. Across all study years, SGA prescriptions were mostly off-label and ordered for aripiprazole, quetiapine, or risperidone. The proportion of off-label indications was highest in 2013 (80.1%) and lowest (69.1%) in 2019. Off-label proportions increased again in 2020 (76.1%) and in 2021 (74.1%). At baseline, patients frequently had other psychotropic prescriptions (e.g., antidepressants 63.3%, stimulants 22.9%, and sedatives/hypnotics 20.7%). Conclusion(s): A general decline in SGA prescribing rates among adolescents was observed from 2013 to 2019, but then increased following Covid-19 onset. Despite known safety risks, off-label use of SGAs remains prominent. Future studies are needed to better understand prescribing outside of pediatric professional society guidelines.Copyright © 2023

Demographic profile and outcome in primary pediatric brain tumors. A single tertiary institute experience in India

Introduction: Pediatric brain tumors are the most common tumor in children after hematological malignancies. There is very few data about the epidemiology of pediatric brain tumors in India. Methods - This was a prospective and retrospective study in pediatric patients who had undergone surgery in our institute (JIPMER,Pondicherry). 80 cases were recruited and followed up for minimum follow up period of 1 year. The demographic profile was analysed and IHC markers were done for embroyonal tumors and glioma. Result(s): Pediatric brain tumors was equally distributed among male and females. (1:1) .Mean age of presentation was 10 years . 27.5 % of our cases were embryonal tumors,low grade glioma (16.25 % ) ,high grade glioma ( 12.5 % ) ,ependymoma and craniopharyngioma comprised 15 % of our cases each. Medulloblastoma comprised 23.75 % of cases Out of which 31.5 % had craniospinal metastasis at time of diagnosis. The most common location of SHH pathway medulloblastoma was cerebellar hemisphere and non WNT/non SHH was fourth ventricle. 45.45 % of patients with high grade glioma had recurrence .50 % of ependymoma cases were infratentorial. we had 2 cases of ganglioglioma ,one in the midbrain and other in temporal lobe .Gross total resection was achieved in 30 % ,Subtotal resection in 46.25 % and partial resection in 20 % of our cases. Outcome of patients at the end of 1 year for low and high grade glioma, ependymoma and craniopharyngioma were similar to western literature. Two patients acquired COVID 19 and died while undergoing treatment. Molecular markers like INI1, LIN28 A was highly sensitive and specific for diagnosing atypical teratoid rhabdoid tumor (ATRT) and embryonal tumor with multilayered rosettes (ETMR )respectively. Conclusion(s): Our study emphasizes the need of standardized and systemic cancer registries in India. (Figure Presented).