Impact of social determinants of health on the outcomes of Latin American children with Multisystem Inflammatory Syndrome (MIS-C).

Importance: There is growing understanding that Social Determinants of Health (SDH) impact on the outcomes of different pediatric conditions. We aimed to determine whether SDH affect the severity of MIS-C.

Design: Retrospective cohort study, 2021-2023.

Heterozygous BTNL8 variants in individuals with multisystem inflammatory syndrome in children (MIS-C).

Multisystem inflammatory syndrome in children (MIS-C) is a rare condition following SARS-CoV-2 infection associated with intestinal manifestations. Genetic predisposition, including inborn errors of the OAS-RNAseL pathway, has been reported. We sequenced 154 MIS-C patients and utilized a novel statistical framework of gene burden analysis, "burdenMC," which identified an enrichment for rare predicted-deleterious variants in BTNL8 (OR = 4.

Plasma cell-free RNA signatures of inflammatory syndromes in children.

Inflammatory syndromes, including those caused by infection, are a major cause of hospital admissions among children and are often misdiagnosed because of a lack of advanced molecular diagnostic tools. In this study, we explored the utility of circulating cell-free RNA (cfRNA) in plasma as an analyte for the differential diagnosis and characterization of pediatric inflammatory syndromes. We profiled cfRNA in 370 plasma samples from pediatric patients with a range of inflammatory conditions, including Kawasaki disease (KD), multisystem inflammatory syndrome in children (MIS-C), viral infections, and bacterial infections.

Cystathionine γ-lyase inhibits mitochondrial oxidative stress by releasing HS nearby through the AKT/NRF2 signaling pathway.

Cystathionine γ-lyase (CSE) is a major enzyme that produces hydrogen sulfide (HS). Herein, we report how CSE plays a previously unknown role in regulating the antioxidant effects of the mitochondria in human umbilical vein endothelial cells by releasing HS nearby under stress conditions. We found that HS partially promoted angiogenesis in the endothelial cells through the AKT/nuclear factor erythroid 2-related factor 2 (AKT/NRF2) signaling pathway.

SARS-CoV-2 variants are associated with different clinical courses in children with MIS-C.

Background: Recent infection with SARS‑CoV‑2 in children has been associated with multisystem inflammatory syndrome in children (MIS-C). SARS‑CoV‑2 has undergone different mutations. Few publications exist about specific variants and their correlation with the severity of MIS-C.

Subgroups of children with Kawasaki disease: a data-driven cluster analysis.

Background: Although Kawasaki disease is commonly regarded as a single disease entity, variability in clinical manifestations and disease outcome has been recognised. We aimed to use a data-driven approach to identify clinical subgroups.

Methods: We analysed clinical data from patients with Kawasaki disease diagnosed at Rady Children's Hospital (San Diego, CA, USA) between Jan 1, 2002, and June 30, 2022.

Multisystem Inflammatory Syndrome in Children (MIS-C) temporally related to COVID-19: the experience at a pediatric reference hospital in Colombia.

Objective: This study aimed to describe the clinical characteristics and the different phenotypes of children with multisystem inflammatory syndrome in children (MIS-C) temporally related to COVID-19 and to evaluate the risk conditions that favored a greater severity of the disease during a 12-month period at a pediatric reference hospital in Colombia.

Methods: A 12-month retrospective observational study of children under the age of 18 years who met criteria for MIS-C.

Results: A total of 28 children presented MIS-C criteria.

Exercise Stress Echocardiography in Kawasaki Disease Patients with Coronary Aneurysms.

The most significant sequelae of Kawasaki disease (KD) are coronary artery aneurysms, which can lead to risk of future myocardial ischemia. Exercise stress echocardiography allows for non-invasive assessment of myocardial dysfunction. We reviewed our single center experience with exercise stress echocardiography in patients with previous history of KD with coronary aneurysms.

Autoantibody discovery across monogenic, acquired, and COVID-19-associated autoimmunity with scalable PhIP-seq.

Phage immunoprecipitation sequencing (PhIP-seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-seq for autoantigen discovery, including our previous work (Vazquez et al., 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls.

Incidence and Severity of Kawasaki Disease Among Vietnamese Children.

Background: Kawasaki disease (KD) disproportionately affects children of Asian descent. San Diego is home to a large Vietnamese population but no previous study has addressed the outcome of KD in this group.

Methods: We performed a retrospective review of Vietnamese patients seen at Rady Children's Hospital San Diego from 2001 to 2019.

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C.

Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5-11, 12-21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron.

Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron and Other Variants in Serum From Children With Vaccination-Induced Myocarditis.

Our study demonstrates that children who developed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination-induced myocarditis and may not receive another vaccination, could be susceptible to infection with Omicron and emerging variants. We observed higher neutralizing antibody titers in myocarditis patients vs. healthy vaccinated children, but significantly lower neutralization titers against Omicron in both groups.

Autoantibody discovery across monogenic, acquired, and COVID19-associated autoimmunity with scalable PhIP-Seq.

Phage Immunoprecipitation-Sequencing (PhIP-Seq) allows for unbiased, proteome-wide autoantibody discovery across a variety of disease settings, with identification of disease-specific autoantigens providing new insight into previously poorly understood forms of immune dysregulation. Despite several successful implementations of PhIP-Seq for autoantigen discovery, including our previous work (Vazquez et al. 2020), current protocols are inherently difficult to scale to accommodate large cohorts of cases and importantly, healthy controls.

Anakinra Treatment in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysms: A Phase I/IIa Trial.

Objectives: To determine the safety, pharmacokinetics, and immunomodulatory effects of 2-6 weeks of anakinra therapy in patients with acute Kawasaki disease with a coronary artery aneurysm (CAA).

Study Design: We performed a Phase I/IIa dose-escalation study of anakinra (2-11 mg/kg/day) in 22 patients with acute Kawasaki disease with CAA. We measured interleukin (IL)-1RA concentrations after the first dose and trough levels up to study week 6.

Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

Background: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth.

Methods: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings.

Hyponatremia in Patients With Multisystem Inflammatory Syndrome in Children.

We report 2 patients with multisystem inflammatory syndrome in children with evidence of hyponatremia on admission. Despite fluid resuscitation and resolution of dehydration, the hyponatremia worsened. Serum and urine studies were evaluated and demonstrated evidence of syndrome of inappropriate antidiuretic hormone.

Review of Cardiac Involvement in Multisystem Inflammatory Syndrome in Children.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) with substantial cardiovascular implications. Although infection with SARS-CoV-2 is usually mild in children, some children later develop a severe inflammatory disease that can have manifestations similar to toxic shock syndrome or Kawasaki disease. This syndrome has been defined by the US Centers for Disease Control and Prevention as multisystem inflammatory syndrome in children.

Biomarkers for the Discrimination of Acute Kawasaki Disease From Infections in Childhood.

Kawasaki disease (KD) is a vasculitis of early childhood mimicking several infectious diseases. Differentiation between KD and infectious diseases is essential as KD's most important complication-the development of coronary artery aneurysms (CAA)-can be largely avoided by timely treatment with intravenous immunoglobulins (IVIG). Currently, KD diagnosis is only based on clinical criteria.

Clinical Characteristics of 58 Children With a Pediatric Inflammatory Multisystem Syndrome Temporally Associated With SARS-CoV-2.

Importance: In communities with high rates of coronavirus disease 2019, reports have emerged of children with an unusual syndrome of fever and inflammation.

Objectives: To describe the clinical and laboratory characteristics of hospitalized children who met criteria for the pediatric inflammatory multisystem syndrome temporally associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (PIMS-TS) and compare these characteristics with other pediatric inflammatory disorders.

Design, Setting, And Participants: Case series of 58 children from 8 hospitals in England admitted between March 23 and May 16, 2020, with persistent fever and laboratory evidence of inflammation meeting published definitions for PIMS-TS.

On the interpretation of the atmospheric mechanism transporting the environmental trigger of Kawasaki Disease.

Recent advances on the environmental determinants of Kawasaki Disease have pointed to the important role of the atmospheric transport of a still unknown agent potentially triggering the disease. The hypothesis arose from an innovative methodology combining expertise in climate dynamics, the analysis of ocean and atmosphere data, the use of dispersion models and the search for biological agents in air samples. The approach offered a new perspective to reveal the identity of the potential trigger, but at the same time, it increased the level of complexity, which could potentially lead to the misinterpretation of the mechanisms.

Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm.

Objectives: To determine the safety, tolerability, pharmacokinetics, and immunomodulatory effects of a 6-week course of atorvastatin in patients with acute Kawasaki disease with coronary artery (CA) aneurysm (CAA).

Study Design: This was a Phase I/IIa 2-center dose-escalation study of atorvastatin (0.125-0.

How Should We Classify Kawasaki Disease?

The exact classification of Kawasaki disease (KD) has been debated. Infectious disease specialists have claimed it as an infection with a classic immune responses to an as yet unidentified pathogen that localizes to the coronary arteries. Others have favored an autoreactive hypothesis that KD is triggered by an antigen that shares homology with structures in the vascular wall, and molecular mimicry resulting in an immune response directed to that tissue.