In rare instances, pediatric SARS-CoV-2 infection results in a novel immunodysregulation syndrome termed multisystem inflammatory syndrome in children (MIS-C). We compared MIS-C immunopathology with severe COVID-19 in adults. MIS-C does not result in pneumocyte damage but is associated with vascular endotheliitis and gastrointestinal epithelial injury. In MIS-C, the cytokine release syndrome is characterized by IFNγ and not type I interferon. Persistence of patrolling monocytes differentiates MIS-C from severe COVID-19, which is dominated by HLA-DRlo classical monocytes. IFNγ levels correlate with granzyme B production in CD16+ NK cells and TIM3 expression on CD38+/HLA-DR+ T cells. Single-cell TCR profiling reveals a skewed TCRβ repertoire enriched for TRBV11-2 and a superantigenic signature in TIM3+/CD38+/HLA-DR+ T cells. Using NicheNet, we confirm IFNγ as a central cytokine in the communication between TIM3+/CD38+/HLA-DR+ T cells, CD16+ NK cells, and patrolling monocytes. Normalization of IFNγ, loss of TIM3, quiescence of CD16+ NK cells, and contraction of patrolling monocytes upon clinical resolution highlight their potential role in MIS-C immunopathogenesis.

BackgroundIn the summer of 2015, the exodus of Syrian war refugees and saturation of refugee camps in neighbouring countries led to the influx of asylum-seekers in European countries, including Belgium. This study aims to describe the demographic and clinical characteristics of asylum seekers who arrived in a huddled refugee camp, in the centre of a well-developed country with all medical facilities.MethodsUsing a descriptive cross-sectional study design, physicians of Médecins du Monde prospectively registered age, gender, origin, medical symptoms and diagnoses of all patients presenting to an erected field hospital in Brussels in September 2015. Diagnoses were post hoc categorised according to the International Classification of Diseases.ResultsOf 4037 patients examined in the field hospital, 3907 were included and analysed for this study. Over 11% of patients suffered from injuries, but these were outnumbered by the proportion of patients with respiratory (36%), dental (9%), skin (9%) and digestive (8%) diagnoses. More than 49% had features of infections at the time of the consultation.ConclusionsAsylum seekers arriving in a refugee camp in Brussels after a long and hazardous journey suffer mostly from respiratory, dental, skin and digestive diseases. Still, one in seven suffers from injury. These findings, consistent with other reports, should be anticipated when composing emergency medical teams and interagency emergency health or similar kits to be used in a field hospital, even in a Western European country.Trial registration numberISRCTN13523620, Results.

Oxygen saturation less than 95%, respiratory frequency more than 45 breaths per minute and age less than 6 months in respiratory-distressed infants are important parameters to predict the need for admission and emphasize the severity of bronchiolitis.

IntroductionCentor criteria (fever >38.5°C, swollen, tender anterior cervical lymph nodes, tonsillar exudate and absence of cough) are an algorithm to assess the probability of group A β haemolytic Streptococcus (GABHS) as the origin of sore throat, developed for adults. We wanted to evaluate the correlation between Centor criteria and presence of GABHS in children with sore throat admitted to our paediatric emergency department (PED).DesignRetrospective cohort study.SettingThe emergency department of a large tertiary university hospital in Brussels, with over 20 000 yearly visits for children below age 16.ParticipantsAll medical records (from 2008 to 2010) of children between ages 2 and 16, who were diagnosed with pharyngitis, tonsillitis or sore throat and having a throat swab culture for GABHS. Children with underlying chronic respiratory, cardiac, haematological or immunological diseases and children who had already received antibiotics (AB) prior to the PED consult were excluded. Only records with a full disease history were selected. Out of a total 2118 visits for sore throats, 441 met our criteria. The children were divided into two age groups, 2–5 and 5–16 years.ResultsThe prevalence of GABHS was higher in the older children compared to the preschoolers (38.7 vs 27.6; p=0.01), and the overall prevalence was 32%. There was no significant difference in the prevalence of GABHS for all different Centor scores within an age group. Likelihood ratios (LR) demonstrate that none of the individual symptoms or a Centor score of ≥3 seems to be effective in ruling in or ruling out GABHS. Pooled LR (CI) for Centor ≥3 was 0.67 (CI 0.50 to 0.90) for the preschoolers and 1.37 (CI 1.04 to 1.79) for the older children.ConclusionsOur results confirm the ineffectiveness of Centor criteria as a predicting factor for finding GABHS in a throat swab culture in children.

Objective: The Syrian civil war since 2011 has led to one of the most complex humanitarian emergencies in history. The objective of this study was to document the impact of the conflict on the familial, educational, and public health state of Syrian children. Methods: A cross-sectional observational study was conducted in May 2015. Health care workers visited families with a prospectively designed data sheet in 4 Northern Syrian governorates. Results: The 1001 children included in this study originated from Aleppo (41%), Idleb (36%), Hamah (15%), and Lattakia (8%). The children's median age was 6 years (range, 0-15 years; interquartile range, 3-11 years), and 61% were boys. Almost 20% of the children were internally displaced, and 5% had deceased or missing parents. Children lacked access to safe drinking water (15%), appropriate sanitation (23%), healthy nutrition (16%), and pediatric health care providers (64%). Vaccination was inadequate in 72%. More than half of school-aged children had no access to education. Children in Idleb and Lattakia were at greater risk of having unmet public health needs. Younger children were at greater risk of having an incomplete vaccination state. Conclusions: After 4 years of civil war in Syria, children have lost parents, live in substandard life quality circumstances, and are at risk for outbreaks because of worsening vaccination states and insufficient availability of health care providers. (Disaster Med Public Health Preparedness. 2016;10:874-882)

BackgroundDuring the 2009 influenza A/H1N1v pandemic, children were identified as a specific "at risk" group. We conducted a multicentric study to describe pattern of influenza A/H1N1v infection among hospitalized children in Brussels, Belgium.MethodsFrom July 1, 2009, to January 31, 2010, we collected epidemiological and clinical data of all proven (positive H1N1v PCR) and probable (positive influenza A antigen or culture) pediatric cases of influenza A/H1N1v infections, hospitalized in four tertiary centers.ResultsDuring the epidemic period, an excess of 18% of pediatric outpatients and emergency department visits was registered. 215 children were hospitalized with proven/probable influenza A/H1N1v infection. Median age was 31 months. 47% had ≥ 1 comorbid conditions. Febrile respiratory illness was the most common presentation. 36% presented with initial gastrointestinal symptoms and 10% with neurological manifestations. 34% had pneumonia. Only 24% of the patients received oseltamivir but 57% received antibiotics. 10% of children were admitted to PICU, seven of whom with ARDS. Case fatality-rate was 5/215 (2%), concerning only children suffering from chronic neurological disorders. Children over 2 years of age showed a higher propensity to be admitted to PICU (16% vs 1%, p = 0.002) and a higher mortality rate (4% vs 0%, p = 0.06). Infants less than 3 months old showed a milder course of infection, with few respiratory and neurological complications.ConclusionAlthough influenza A/H1N1v infections were generally self-limited, pediatric burden of disease was significant. Compared to other countries experiencing different health care systems, our Belgian cohort was younger and received less frequently antiviral therapy; disease course and mortality were however similar.

Aims: To look at the association between level of social deprivation and incidence of penetrating trauma in children in London.

Background Meningitis can be caused by several viruses and bacteria. Identifying the causative pathogen as quickly as possible is crucial to initiate the most optimal therapy, as acute bacterial meningitis is associated with a significant morbidity and mortality. Bacterial meningitis requires antibiotics, as opposed to enteroviral meningitis, which only requires supportive therapy. Clinical presentation is usually not sufficient to differentiate between viral and bacterial meningitis, thereby necessitating cerebrospinal fluid (CSF) analysis by PCR and/or time-consuming bacterial cultures. However, collecting CSF in children is not always feasible and a rather invasive procedure. Methods In 12 Belgian hospitals, we obtained acute blood samples from children with signs of meningitis (49 viral and 7 bacterial cases) (aged between 3 months and 16 years). After pathogen confirmation on CSF, the patient was asked to give a convalescent sample after recovery. 3′ mRNA sequencing was performed to determine differentially expressed genes (DEGs) to create a host transcriptomic profile. Results Enteroviral meningitis cases displayed the largest upregulated fold change enrichment in type I interferon production, response and signaling pathways. Patients with bacterial meningitis showed a significant upregulation of genes related to macrophage and neutrophil activation. We found several significantly DEGs between enteroviral and bacterial meningitis. Random forest classification showed that we were able to differentiate enteroviral from bacterial meningitis with an AUC of 0.982 on held-out samples. Conclusions Enteroviral meningitis has an innate immunity signature with type 1 interferons as key players. Our classifier, based on blood host transcriptomic profiles of different meningitis cases, is a possible strong alternative for diagnosing enteroviral meningitis.