Febrile children with comorbidities at the emergency department - a multicentre observational study.

We aimed to describe characteristics and management of children with comorbidities attending European emergency departments (EDs) with fever. MOFICHE (Management and Outcome of Fever in children in Europe) is a prospective multicentre study (12 European EDs, 8 countries). Febrile children with comorbidities were compared to those without in terms of patient characteristics, markers of disease severity, management, and diagnosis. Comorbidity was defined as a chronic underlying condition that is expected to last > 1 year. We performed multivariable logistic regression analysis, displaying adjusted odds ratios (aOR), adjusting for patient characteristics. We included 38,110 patients, of whom 5906 (16%) had comorbidities. Most common comorbidities were pulmonary, neurologic, or prematurity. Patients with comorbidities more often were ill appearing (20 versus 16%, p < 0.001), had an ED-Paediatric Early Warning Score of > 15 (22 versus 12%, p < 0.001), or a C-reactive protein > 60 mg/l (aOR 1.4 (95%CI 1.3-1.6)). They more often required life-saving interventions (aOR 2.7, 95% CI 2.2-3.3), were treated with intravenous antibiotics (aOR 2.3, 95%CI 2.1-2.5), and were admitted to the ward (aOR 2.2, 95%CI 2.1-2.4) or paediatric intensive care unit (PICU) (aOR 5.5, 95% CI 3.8-7.9). They were more often diagnosed with serious bacterial infections (aOR 1.8, 95%CI 1.7-2.0), including sepsis/meningitis (aOR 4.6, 95%CI 3.2-6.7). Children most at risk for sepsis/meningitis were children with malignancy/immunodeficiency (aOR 14.5, 8.5-24.8), while children with psychomotor delay/neurological disease were most at risk for life-saving interventions (aOR 5.3, 4.1-6.9) or PICU admission (aOR 9.7, 6.1-15.5). CONCLUSIONS: Our data show how children with comorbidities are a population at risk, as they more often are diagnosed with bacterial infections and more often require PICU admission and life-saving interventions. WHAT IS KNOWN: • While children with comorbidity constitute a large part of ED frequent flyers, they are often excluded from studies. WHAT IS NEW: • Children with comorbidities in general are more ill upon presentation than children without comorbidities. • Children with comorbidities form a heterogeneous group; specific subgroups have an increased risk for invasive bacterial infections, while others have an increased risk of invasive interventions such as PICU admission, regardless of the cause of the fever.

Biomarkers for Diagnosing Febrile Illness in Immunocompromised Children: A Systematic Review of the Literature.

Objective: This study aims to assess the performance of biomarkers used for the prediction of bacterial, viral, and fungal infection in immunocompromised children upon presentation with fever. Methods: We performed a literature search using PubMed and MEDLINE and In-Process & Other Non-indexed Citations databases. Cohort and case-control studies assessing biomarkers for the prediction of bacterial, viral, or fungal infection in immunocompromised children vs. conventional microbiological investigations were eligible. Studies including adult patients were eligible if pediatric data were separately assessable. Data on definitions used for infections, fever, and neutropenia and predictive values were collected. Risk of bias was assessed with the Quality Assessment of Diagnostic Accuracy Studies-2 tool. Results: Fifty-two studies involving 13,939 febrile episodes in 7,059 children were included. In total, 92.2% were in cancer patients (n = 48), and 15.7% also included hematopoietic stem cell transplantation patients (n = 8). Forty-three biomarkers were investigated, of which 6 (CRP, PCT, IL-8, IL-6, IL-10, and TNFα) were significantly associated with bacterial infection at admission, studied in multiple studies, and provided predictive data. Literature on the prediction of viral and fungal infection was too limited. Eight studies compared C-reactive protein (CRP) and procalcitonin (PCT), with PCT demonstrating superiority in 5. IL-6, IL-8, and IL-10 were compared with CRP in six, four, and one study, respectively, with mixed results on diagnostic superiority. No clear superior biomarker comparing PCT vs. IL-6, IL-8, or IL-10 was identified. Discussion: There is great heterogeneity in the biomarkers studied and cutoff values and definitions used, thus complicating the analysis. Literature for immunocompromised children with non-malignant disease and for non-bacterial infection is sparse. Literature on novel diagnostics was not available. We illustrated the challenges of diagnosing fever adequately in this study population and the need for improved biomarkers and clinical decision-making tools.

Case Report: Severe Acute Pulmonary COVID-19 in a Teenager Post Autologous Hematopoietic Stem Cell Transplant.

Pulmonary severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children is generally described as mild, and SARS-CoV-2 infection in immunocompromised children are observed as generally mild as well. A small proportion of pediatric patients will become critically ill due to (cardio)respiratory failure and require intensive care treatment. We report the case of a teenager with Hodgkin's lymphoma who acquired SARS-CoV-2 (detected by PCR) on the day of her autologous stem cell transplant and developed acute respiratory distress syndrome, successfully treated with a combination of antivirals, immunomodulation with steroids and biologicals, and ECMO.