Children with SARS-CoV-2 related Multisystem Inflammatory Syndrome in Children (MIS-C) often present with clinical features that resemble Kawasaki disease (KD). Disease severity in adult COVID-19 is associated to the presence of anti-cytokine autoantibodies (ACAAs) against type I interferons. Similarly, ACAAs may be implicated in KD and MIS-C. Therefore, we explored the immunological response, presence of ACAAs and disease correlates in both disorders. Eighteen inflammatory plasma protein levels and seven ACAAs were measured in KD (n = 216) and MIS-C (n = 56) longitudinally by Luminex and/or ELISA. Levels (up to 1 year post-onset) of these proteins were related to clinical data and compared with healthy paediatric controls. ACAAs were found in both patient groups. The presence of ACAAs lagged behind the inflammatory plasma proteins and peaked in the subacute phase. ACAAs were mostly directed against IFN-γ (>80%) and were partially neutralising at best. KD presented with a higher variety of ACAAs than MIS-C. Increased levels of anti-IL-17A (P = 0·02) and anti-IL-22 (P = 0·01) were inversely associated with ICU admission in MIS-C. Except for CXCL10 in MIS-C (P = 0·002), inflammatory plasma proteins were elevated in both KD and MIS-C. Endothelial angiopoietin-2 levels were associated with coronary artery aneurysms in KD (P = 0·02); and sCD25 (P = 0·009), angiopoietin-2 (P = 0·001), soluble IL-33-receptor (ST2, P = 0·01) and CXCL10 (P = 0·02) with ICU admission in MIS-C. Markers of endothelial activation (E-selectin, angiopoietin-2), and innate and adaptive immune responses (macrophages [CD163, G-CSF], neutrophils [lipocalin-2], and T cells [IFN-γ, CXCL10, IL-6, IL-17]), are upregulated in KD and MIS-C. ACAAs were detected in both diseases and, although only partly neutralising, their transient presence and increased levels in non-ICU patients may suggest a dampening role on inflammation. The Kawasaki study is funded by the Dutch foundation Fonds Kind & Handicap and an anonymous donor. The sponsors had no role in the study design, analysis, or decision for publication.

The clinical phenotype of severe acute asthma at the Paediatric Intensive Care Unit (PICU) is highly heterogeneous. However, current treatment is still based on a ‘one size fits all approach’.We ai...

Background: The incidence of severe asthma exacerbations (SAE) requiring a pediatric intensive care unit (PICU) admission during the coronavirus disease 2019 (COVID‐19) pandemic (and its association with public restrictions) is largely unknown. We examined the trend of SAE requiring PICU admission before, during, and after COVID‐19 restrictions in Amsterdam, the Netherlands, and its relationship with features such as environmental triggers and changes in COVID‐19 restriction measures.Methods: In this single‐center, retrospective cohort study, all PICU admissions of children aged ≥2 years for severe asthma at the Amsterdam UMC between 2018 and 2022 were included. The concentrations of ambient fine particulate matter (PM_2.5) and pollen were obtained from official monitoring stations.Results: Between January 2018 and December 2022, 228 children were admitted to the PICU of the Amsterdam UMC for SAE. While we observed a decrease in admissions during periods of more stringent restriction, there was an increase in the PICU admission rate for SAE in some periods following the lifting of restrictions. In particular, following the COVID‐19 restrictions in 2021, we observed a peak incidence of admissions from August to November, which was higher than any other peak during the indicated years. No association with air pollution or pollen was observed.Conclusion: We hypothesize that an increase in clinically diagnosed viral infections after lockdown periods was the reason for the altered incidence of SAE at the PICU in late 2021, rather than air pollution and pollen concentrations.

Context: The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. Objective: The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants and PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children's respiratory diseases at the PICU. Methods: A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. Results: Eight thousand seven hundred fourty‐six references were reviewed, and 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. Conclusion: Disparities in socioeconomic (such as a low‐income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children's respiratory diseases and can negatively influence the outcomes of these children admitted and treated at the PICU.

Background: Severe acute asthma (SAA) in children can be life-threatening. There has been a significant rise in paediatric intensive care unit (PICU) admissions due to SAA over the past two decades. While asthma is a heterogeneous disease, its underlying pathophysiological pathways remain underexplored. This study aimed to assess the value of non-invasive targeted exhaled breath metabolomics analysis to better characterise SAA. Methods: Breath samples from 17 children admitted to the PICU with SAA (cases) and 27 children with controlled severe asthma (controls) were analysed using thermal desorption gas chromatography–mass spectrometry (TD-GC-MS). Results: A targeted volatile organic compound (VOC) analysis identified 25 compounds, of which 16 were shared between groups. Four VOCs were significantly more often present in SAA, and nine VOCs exhibited higher concentrations in SAA. Longitudinal analysis of VOCs from follow-up samples of 10 cases showed no significant temporal differences, reinforcing the reproducibility of identified biomarkers. Conclusions: This study exemplifies the potential of exhaled breath analysis to provide insights into the molecular background of SAA. Breath metabolomics may enable early recognition of severe asthma attacks and preventive therapeutic interventions in children with severe asthma.