Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study.

INTRODUCTION: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology investigation of the systemic immune response in neonates to sepsis identified immune and metabolic markers that showed high accuracy for detecting bacterial infection. Further gene expression markers have also been reported previously in the paediatric age group for discriminating sepsis from control cases. More recently, specific gene signatures were identified to discriminate between COVID-19 and its associated inflammatory sequelae. Through the current prospective cohort study, we aim to evaluate immune and metabolic blood markers which discriminate between sepses (including COVID-19) from other acute illnesses in critically unwell children and young persons, up to 18 years of age. METHODS AND ANALYSIS: We describe a prospective cohort study for comparing the immune and metabolic whole-blood markers in patients with sepsis, COVID-19 and other illnesses. Clinical phenotyping and blood culture test results will provide a reference standard to evaluate the performance of blood markers from the research sample analysis. Serial sampling of whole blood (50 µL each) will be collected from children admitted to intensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent. ETHICS AND DISSEMINATION: The study has received research ethics committee approval from the Yorkshire and Humber Leeds West Research Ethics Committee 2 (reference 20/YH/0214; IRAS reference 250612). Submission of study results for publication will involve making available all anonymised primary and processed data on public repository sites. TRIAL REGISTRATION NUMBER: NCT04904523.

Sleep and adverse environmental factors in sedated mechanically ventilated pediatric intensive care patients.

OBJECTIVE: To document the quantity and architecture of sleep using objective electrophysiologic assessment in sedated mechanically ventilated pediatric intensive care unit patients over a 24-hr period and to investigate the effect of noise and staff interventions on sleep pattern in these subjects. DESIGN: Prospective observational study. SETTING: Pediatric intensive care unit at a university hospital. PATIENTS: A total of 11 patients studied between September 2000 and June 2001, with ages ranging from 3 to 21 months. All patients were intubated, mechanically ventilated, and sedated with morphine and midazolam infusions. INTERVENTIONS: Limited sleep polysomnograph, staff interventions, and noise levels were continuously monitored during a 24-hr period. MEASUREMENTS AND MAIN RESULTS: Noise levels were consistently >48 dB(A); the highest night peak reached 103 dB(A). Staff interventions lasted for a mean of 240 (SD 90) mins in a 24-hr period. There was no significant difference in the number of interventions between day and night. Severe alterations to sleep architecture were found throughout the 24 hrs, with no diurnal variations. Active sleep was severely reduced to a mean of 3% (SD 4%; range, 0-11%) of total sleep time. There was severe sleep fragmentation as reflected by the high number (mean, 40 [SD 20]) of wake episodes. CONCLUSION: The above findings suggest a significant electrophysiologic abnormality of sleep in the pediatric intensive care unit patients. Our pediatric intensive care unit environment is characterized by both, high noise levels and frequent staff interventions. This study has several limitations and future studies are needed, with larger sample size and an attempt to manipulate the environmental factors to minimize their negative effects on sleep.