No abstract

We describe 3 patients with HLH and FIRES. The co-occurrence of these 2 rare disorders suggests the possibility of a common immune dysregulation phenotype prolonging epileptogenesis. HLH screening in critically ill patients with FIRES may yield a broader understanding of shared inflammatory processes.

Differential host responses in coronavirus disease 2019 (COVID-19) and multisystem inflammatory syndrome in children (MIS-C) remain poorly characterized. Here we use next-generation sequencing to longitudinally analyze blood samples from pediatric patients with acute COVID-19 (n=70) or MIS-C (n=141) across three hospitals. Profiling of plasma cell-free nucleic acids uncovers distinct signatures of cell injury and death between these two disease states, with increased heterogeneity and multi-organ involvement in MIS-C encompassing diverse cell types such as endothelial and neuronal Schwann cells. Whole blood RNA profiling reveals upregulation of similar pro-inflammatory signaling pathways in COVID-19 and MIS-C, but also MIS-C specific downregulation of T cell-associated pathways. Profiling of plasma cell-free RNA and whole blood RNA in paired samples yields different yet complementary signatures for each disease state. Our work provides a systems-level, multi-analyte view of immune responses and tissue damage in COVID-19 and MIS-C and informs the future development of new disease biomarkers.

BackgroundDespite similar rates of infection, adults and children have markedly different morbidity and mortality related to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Compared to adults, children have infrequent severe manifestations of acute infection but are uniquely at risk for the rare and often severe Multisystem Inflammatory Syndrome in Children (MIS-C) following infection. We hypothesized that these differences in presentation are related to differences in the magnitude and/or antigen specificity of SARS-CoV-2-specific T cell (CST) responses between adults and children. We therefore set out to measure the CST response in convalescent adults versus children with and without MIS-C following SARS-CoV-2 infection.MethodsCSTs were expanded from blood collected from convalescent children and adults post SARS-CoV-2 infection and evaluated by intracellular flow cytometry, surface markers, and cytokine production following stimulation with SARS-CoV-2-specific peptides. Presence of serum/plasma antibody to spike and nucleocapsid was measured using the luciferase immunoprecipitation systems (LIPS) assay.FindingsTwenty-six of 27 MIS-C patients, 7 of 8 non-MIS-C convalescent children, and 13 of 14 adults were seropositive for spike and nucleocapsid antibody. CST responses in MIS-C patients were significantly higher than children with uncomplicated SARS-CoV-2 infection, but weaker than CST responses in convalescent adults.InterpretationAge-related differences in the magnitude of CST responses suggest differing post-infectious immunity to SARS-CoV-2 in children compared to adults post uncomplicated infection. Children with MIS-C have CST responses that are stronger than children with uncomplicated SARS-CoV-2 infection and weaker than convalescent adults, despite near uniform seropositivity.

Objectives: A gluten-free (GF) diet is the primary treatment for celiac disease (CD). Gluten is used in schools, particularly in early childhood, art, and home-economics classrooms. This study aimed to measure gluten transfer from school supplies to GF foods that a child with CD may eat. Also, to measure efficacy of washing techniques to remove gluten from hands and tables. Methods: Five experiments measured potential gluten cross-contact in classrooms: Play-Doh (n = 30); baking project (n = 30); paper mâché (n = 10); dry pasta in sensory table (n = 10); cooked pasta in sensory table (n = 10). Thirty participants ages 2 to 18 were enrolled. Following activities, gluten levels were measured on separate slices of GF bread rubbed on participant's hands and table surfaces. Participants were assigned 1 of 3 handwashing methods (soap and water, water alone, or wet wipe). Repeat gluten transfer measurements were taken from hands and tables. Gluten measurements made using R-Biopharm R7001 R5-ELISA Sandwich assay. Results: Paper mâché, cooked pasta in sensory tables, and baking project resulted in rates of gluten transfer far greater than the 20 ppm threshold set by Codex Alimentarius Commission. Play-Doh and dry pasta, however, resulted in few gluten transfers to GF bread >20 ppm. Soap and water was consistently the most effective method for removing gluten, although other methods proved as effective in certain scenarios. Conclusions: The potential for gluten exposure at school is high for some materials and low for others. For high-risk materials, schools should provide GF supplies and have a robust strategy to prevent gluten cross-contact with food.