BACKGROUND:Bronchiolitis is a common viral respiratory disease of infants, with severity ranging from mild symptoms, such as coryza and feeding difficulties, to fulminant respiratory failure. Endotracheal administration of exogenous surfactant has been shown in small studies to improve gas exchange in critically ill infants with bronchiolitis. We aimed to investigate the safety and efficacy of endotracheal poractant alfa for treating critical bronchiolitis compared with a sham procedure. METHODS:BESS was a multicentre, blinded, randomised, sham-controlled, parallel-group, phase 2, superiority trial with exploratory mechanism evaluation studies. The trial was done in 15 paediatric intensive care units in the devolved National Health Service (NHS) of England, Scotland, and Northern Ireland. Preterm and term-born infants younger than 26 weeks of gestationally corrected age admitted to hospitals with bronchiolitis requiring invasive mechanical ventilation (IMV) were randomly assigned (1:1) to receive up to three doses of endotracheal poractant alfa (Curosurf) or sham intervention, allocated through web-based randomisation. Randomisation was stratified by duration of IMV before randomisation (<24 h and ≥24 h) and by site. The infants and their families, clinical care staff, Liverpool Clinical Trial Centre staff, and members of the site research teams were masked to treatment allocations. Endotracheal poractant alfa was given initially at 200 mg/kg, followed by 100 mg/kg at 12 h intervals. The primary endpoint was the duration of IMV from randomisation to final successful extubation. All infants who were successfully extubated were included in the intention-to-treat analysis. Safety outcomes were analysed in infants who had received at least one trial intervention. This trial was registered prospectively with ISRCTN (ISRCTN11746266) and EudraCT (2018-001169-18), and is completed. FINDINGS:The trial was completed after six recruitment seasons. Between Dec 18, 2018, to March 31, 2024, 1009 infants were assessed for eligibility, 232 of whom were randomly assigned to receive either endotracheal poractant alfa (n=115) or a sham intervention (n=117). 130 (56%) of 232 infants were male and 102 (44%) were female. Three infants were withdrawn from the study. None were lost to follow-up. The median duration of IMV was 64·9 h (IQR 43·2-92·1) in the endotracheal poractant alfa group and 62·0 h (39·3-95·1) in the sham intervention group. The geometric mean ratio was 1·02 (95% CI 0·84-1·24; t-test p=0·86). No clinically significant safety issues were associated with endotracheal poractant alfa and there were no deaths. INTERPRETATION:Poractant alfa, administered endotracheally to infants with early critical bronchiolitis, although safe, did not reduce the duration of IMV compared with the sham intervention. Therefore, our findings suggest that it should not be used for this indication at this dose and administration method. FUNDING:UK National Institute for Health and Care Research, UK Research and Innovation Medical Research Council, Chief Scientist Office Scotland, Health and Social Care Research and Development Division Northern Ireland, and Chiesi Farmaceutici, Italy.

OBJECTIVE:To investigate SARS-CoV-2 vaccine uptake and effectiveness in children and young people (CYP) with life-limiting neurodisability. DESIGN:We undertook a retrospective cohort study using national hospital data in England from 21 December 2020 to 2 September 2022 to describe SARS-CoV-2 vaccination uptake, and then examined COVID-19 hospitalisation, paediatric intensive care unit (PICU) admission and death following SARS-CoV-2 infection by vaccination status using Cox regression models. PATIENTS:CYP aged 5-17 with life-limiting neurodisability. RESULTS:We identified 38 067 CYP with life-limiting neurodisability; 13 311 (35.0%) received at least one SARS-CoV-2 vaccine, with uptake higher among older, white CYP, from less deprived neighbourhoods. Of 8134 CYP followed up after a positive SARS-CoV-2 test, 1547 (19%) were vaccinated. Within 28 days of infection, 309 (4.7%) unvaccinated CYP were hospitalised with COVID-19 compared with 75 (4.8%) vaccinated CYP. 46 (0.7%) unvaccinated CYP were admitted to PICU compared with 10 (0.6%) vaccinated CYP. 20 CYP died within 28 days of SARS-CoV-2 infection, of which 13 were unvaccinated. Overall, adjusted hazard of hospitalisation for COVID-19 or admission to PICU did not vary by vaccination status. When the Alpha-Delta SARS-CoV-2 variants were dominant, hazard of hospitalisation with COVID-19 was significantly lower among vaccinated CYP (HR 0.26 (0.09 to 0.74)), with no difference seen during Omicron (HR 1.16 (0.74 to 1.81)). CONCLUSIONS:SARS-CoV-2 vaccination was protective of COVID-19 hospitalisation among CYP with life-limiting neurodisability during Alpha-Delta, but not for other SARS-CoV-2 variants. Vaccine uptake was low and varied by ethnicity and deprivation.

Background:Despite the increasing use of non-invasive respiratory support in paediatric intensive care units, there are no large randomised controlled trials comparing two commonly used non-invasive respiratory support modes, continuous positive airway pressure and high-flow nasal cannula therapy. Objective:To evaluate the non-inferiority of high-flow nasal cannula, compared with continuous positive airway pressure, when used as the first-line mode of non-invasive respiratory support in acutely ill children and following extubation, on time to liberation from respiratory support, defined as the start of a 48-hour period during which the child was free of respiratory support (non-invasive and invasive). Design:A master protocol comprising two pragmatic, multicentre, parallel-group, non-inferiority randomised controlled trials (step-up and step-down) with shared infrastructure, including internal pilot and integrated health economic evaluation. Setting:Twenty-five National Health Service paediatric critical care units (paediatric intensive care units and/or high-dependency units) across England, Wales and Scotland. Participants:Critically ill children assessed by the treating clinician to require non-invasive respiratory support for (1) acute illness (step-up randomised controlled trial) or (2) within 72 hours of extubation (step-down randomised controlled trial). Interventions:High-flow nasal cannula delivered at a flow rate based on patient weight (Intervention) compared to continuous positive airway pressure of 7-8 cm H2O pressure (Control). Main outcome measures:The primary clinical outcome was time to liberation from respiratory support. The primary cost-effectiveness outcome was 180-day incremental net monetary benefit. Secondary outcomes included mortality at paediatric intensive care unit/high-dependency unit discharge, day 60 and day 180; (re)intubation rate at 48 hours; duration of paediatric intensive care unit/high-dependency unit and hospital stay; patient comfort; sedation use; parental stress; and health-related quality of life at 180 days. Results:In the step-up randomised controlled trial, out of 600 children randomised, 573 were included in the primary analysis (median age 9 months). Median time to liberation was 52.9 hours for high-flow nasal cannula (95% confidence interval 46.0 to 60.9 hours) and 47.9 hours (95% confidence interval 40.5 to 55.7 hours) for continuous positive airway pressure (adjusted hazard ratio 1.03, one-sided 97.5% confidence interval 0.86 to ∞). The high-flow nasal cannula group had lower use of sedation (27.7% vs. 37%) and mean duration of acute hospital stay (13.8 days vs. 19.5 days). In the step-down randomised controlled trial, of the 600 children randomised, 553 were included in the primary analysis (median age 3 months). Median time to liberation for high-flow nasal cannula was 50.5 hours (95% confidence interval, 43.0 to 67.9) versus 42.9 hours (95% confidence interval 30.5 to 48.2) for continuous positive airway pressure (adjusted hazard ratio 0.83, one-sided 97.5% confidence interval 0.70 to ∞). Mortality at day 180 was significantly higher for high-flow nasal cannula [5.6% vs. 2.4% for continuous positive airway pressure, adjusted odds ratio, 3.07 (95% confidence interval, 1.1 to 8.8)]. Limitations:The interventions were unblinded. A heterogeneous cohort of children with a range of diagnoses and severity of illness were included. Conclusions:Among acutely ill children requiring non-invasive respiratory support, high-flow nasal cannula met the criterion for non-inferiority compared with continuous positive airway pressure for time to liberation from respiratory support whereas in critically ill children requiring non-invasive respiratory support following extubation, the non-inferiority of high-flow nasal cannula could not be demonstrated. Future work:(1) Identify risk factors for treatment failure. (2) Compare protocolised approaches to post-extubation non-invasive respiratory support, with standard care. (3) Explore alternative approaches for evaluating heterogeneity of treatment effect. (4) Explore reasons for increased mortality in high-flow nasal cannula group within step-down randomised controlled trial. Study registration:Current Controlled Trials ISRCTN60048867. Funding:This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 17/94/28) and is published in full in Health Technology Assessment; Vol. 29, No. 9. See the NIHR Funding and Awards website for further award information.

OBJECTIVE:Following very preterm birth, some children require ongoing intensive care after the neonatal period and transition directly from neonatal units (NNUs) to paediatric intensive care units (PICUs) around term-corrected age.We aimed to understand, at a national level, characteristics and outcomes of children born very preterm who transitioned directly from NNUs to PICUs. DESIGN:Retrospective cohort study, using data linkage of National Neonatal Research Database, Paediatric Intensive Care Audit Network and Office for National Statistics datasets. SETTING:All NNUs and PICUs in England and Wales. PATIENTS:Children born <32 gestational weeks between 1 January 2013 and 31 December 2018, admitted to NNUs, and who transitioned directly to PICU without return to NNU at ≥36 weeks corrected gestation age were included. MAIN OUTCOME MEASURES:Mortality, length of PICU stay, invasive ventilation in PICU (including via tracheostomy), PICU readmission until 2 years of age. RESULTS:Direct NNU-to-PICU transitions occurred in 276 babies during the study period. An increasing yearly trend was observed: 36 transitions of babies born in 2013, 65 in 2018.Of this cohort, 22% of children died before their second birthday, 59% of survivors had ≥1 PICU readmission, 33% of children had long stays in PICU (≥28 days) and 25% received tracheostomy ventilation. CONCLUSIONS:An increasing number of very preterm children require ongoing intensive care at the end of their neonatal stay, with high rates of mortality and morbidity. Multidisciplinary involvement and planning around the time of transition from NNU to PICU, informed by national guidance, may be beneficial.

Objective To quantify the characteristics of children admitted to neonatal units (NNUs) and paediatric intensive care units (PICUs) before the age of 2 years. Design A data linkage study of routinely collected data. Setting National Health Service NNUs and PICUs in England and Wales Patients Children born from 2013 to 2018. Interventions None. Main outcome measure Admission to PICU before the age of 2 years. Results A total of 384 747 babies were admitted to an NNU and 4.8% (n=18 343) were also admitted to PICU before the age of 2 years. Approximately half of all children admitted to PICU under the age of 2 years born in the same time window (n=18 343/37 549) had previously been cared for in an NNU. The main reasons for first admission to PICU were cardiac (n=7138) and respiratory conditions (n=5386). Cardiac admissions were primarily from children born at term (n=5146), while respiratory admissions were primarily from children born preterm (<37 weeks’ gestational age, n=3550). A third of children admitted to PICU had more than one admission. Conclusions Healthcare professionals caring for babies and children in NNU and PICU see some of the same children in the first 2 years of life. While some children are following established care pathways (eg, staged cardiac surgery), the small proportion of children needing NNU care subsequently requiring PICU care account for a large proportion of the total PICU population. These differences may affect perceptions of risk for this group of children between NNU and PICU teams.

OBJECTIVE:To propose a rational basis for donor testing in cases of suspected antibody-mediated transfusion-related lung injury (AMT). BACKGROUND:Anti-leukocyte antibodies in donated blood are established causes of transfusion-related lung injury (TRALI). However, the question of whether to test donors for antibodies is not identical to whether the case meets definition criteria for TRALI. There is a balance between the potential benefits of testing and the costs of donor deferral and investigation. We propose that a decision-making process based on optimising the balance between risk and benefit requires a subjective choice of the relative value of different outcomes of testing. METHODS:We have developed a formal decision model to illustrate how these choices affect testing decisions. RESULTS:Using a Bayesian probability model, we show that the diagnostic benefit and TRALI prevention benefit of testing donors have a complex interrelationship with the number of implicated donors and clinical suspicion of antibody-mediated TRALI (AMT) and that rational testing choices vary according to value assigned to outcomes. CONCLUSIONS:The challenges to the use of a formal decision model for clinical testing are discussed and conclude that a formal model is a useful consensus-building tool for improving consistency and openness in decision making.

OBJECTIVE:Survival of babies born very preterm (<32 weeks gestational age) has increased, although preterm-born children may have ongoing morbidity. We aimed to investigate the risk of admission to paediatric intensive care units (PICUs) of children born very preterm following discharge home from neonatal care.DESIGN:Retrospective cohort study, using data linkage of National Neonatal Research Database and the Paediatric Intensive Care Audit Network datasets.SETTING:All neonatal units and PICUs in England and Wales.PATIENTS:Children born very preterm between 1 January 2013 and 31 December 2018 and admitted to neonatal units.MAIN OUTCOME MEASURES:Admission to PICU after discharge home from neonatal care, before 2 years of age.RESULTS:Of the 40 690 children discharged home from neonatal care, there were 2308 children (5.7%) with at least one admission to PICU after discharge. Of these children, there were 1901 whose first PICU admission after discharge was unplanned.The percentage of children with unplanned PICU admission varied by gestation, from 10.2% of children born <24 weeks to 3.3% born at 31 weeks.Following adjustment, unplanned PICU admission was associated with lower gestation, male sex (adjusted OR (aOR) 0.79), bronchopulmonary dysplasia (aOR 1.37), necrotising enterocolitis requiring surgery (aOR 1.39) and brain injury (aOR 1.42). For each week of increased gestation, the aOR was 0.90.CONCLUSIONS:Most babies born <32 weeks and discharged home from neonatal care do not require PICU admission in the first 2 years. The odds of unplanned admissions to PICU were greater in the most preterm and those with significant neonatal morbidity.

High flow nasal cannula therapy (HFNC) and continuous positive airway pressure (CPAP) are two widely used modes of non-invasive respiratory support in paediatric critical care units. The FIRST-ABC randomised controlled trials (RCTs) evaluated the clinical and cost-effectiveness of HFNC compared with CPAP in two distinct critical care populations: acutely ill children (‘step-up’ RCT) and extubated children (‘step-down’ RCT). Clinical effectiveness findings (time to liberation from all forms of respiratory support) showed that HFNC was non-inferior to CPAP in the step-up RCT, but failed to meet non-inferiority criteria in the step-down RCT. This study evaluates the cost-effectiveness of HFNC versus CPAP. All-cause mortality, health-related Quality of Life (HrQoL), and costs up to six months were reported using FIRST-ABC RCTs data. HrQoL was measured with the age-appropriate Paediatric Quality of Life Generic Core Scales questionnaire and mapped onto the Child Health Utility 9D index score at six months. Quality-Adjusted Life Years (QALYs) were estimated by combining HrQoL with mortality. Costs at six months were calculated by measuring and valuing healthcare resources used in paediatric critical care units, general medical wards and wider health service. The cost-effectiveness analysis used regression methods to report the cost-effectiveness of HFNC versus CPAP at six months and summarised the uncertainties around the incremental cost-effectiveness results. In both RCTs, the incremental QALYs at six months were similar between the randomised groups. The estimated incremental cost at six months was − £4565 (95

BACKGROUND Children experiencing critical illness or injury may require admission to a paediatric intensive care unit (PICU) to receive life-sustaining or life-saving treatment. Studies have explored the experience of parents with a child in PICU but tend to focus on subgroups of children or specific healthcare systems. Therefore, we aimed to undertake a meta-ethnography to draw together the published research. METHODS A systematic search strategy was developed to identify qualitative studies, which had explored the experiences of parents with a critically ill child treated in a PICU. A meta-ethnography was undertaken following the structured steps of identifying the topic; undertaking a systematic search; reading the research; determining how the studies relate and translate into each other; and synthesising and expressing the results. RESULTS We identified 2989 articles from our search and after a systematic series of exclusions, 15 papers remaining for inclusion. We explored the original parent voices (first order) and the interpretation of the study authors (second order) to identify three third-order concepts (our interpretation of the findings), which related to technical, relational and temporal factors. These factors influenced parents' experiences, providing both barriers and facilitators to how parents and caregivers experienced the time their child was in the PICU. The dynamic and co-constructed nature of safety provided an analytical overarching frame of reference. CONCLUSION This synthesis demonstrates novel ways in which parents and caregivers can contribute to the vital role of ensuring a co-created safe healthcare environment for their child when receiving life-saving care within the PICU.

The presentation of a neonate with poor feeding and respiratory distress is a common paediatric scenario. While acute myocarditis is an uncommon cause of this presentation, rapid recognition and intensive care support gives these infants the best possible chance of survival. During September–December 2022, eight infants were admitted to paediatric intensive care units (PICUs) in the Southwest of England and South Wales with neonatal enterovirus myocarditis (NEM). All eight neonates presented acutely in extremis with reduced feeding, tachypnoea and cardiogenic shock. Two initially had enteroviral meningitis. Seven had laboratory features of haemophagocytic lymphohistiocytosis (HLH) (table 1). Enterovirus was detected in all patients. They had severe left ventricular dysfunction on initial echocardiography. Electrocardiography demonstrated widespread Q waves, low voltage R waves and ST segment abnormalities. Due to the severity of their condition, clinical trajectory and evidence of inflammation, immunomodulation and antiviral therapy (where possible) were commenced. Extracorporeal membrane oxygenation was considered in five patients, but it was deemed inappropriate because of poor prognosis and very likely prolonged time to recovery. Use of ventricular assist device was not an option for infants this age/size. Enterovirus is a common cause of neonatal infection but rarely causes myocarditis and secondary HLH. In NEM, the most frequently identified serotypes are coxsackievirus B, with a mortality rate of 40%. These infants are at high risk of arrhythmias. A study from a tertiary paediatric hospital in the Netherlands identified seven NEM cases over 14 years, suggesting that it is uncommon (incidence rate 3.1/100 000 personyears). 4 Here we report a cluster of eight NEM cases admitted over 12 weeks (incidence rate 38.5/100 000 personyears). This is significantly higher than previously observed (incidence rate ratio 12.3; 95% CI 4.47 to 33.98) and our centres’ past experience. While there is no agreed treatment for NEM, evidence from cardiac biopsies suggests direct damage to myocytes with enterovirus replication and inflammatory infiltration. The evidence on the use of intravenous immunoglobulin (IVIG), immunomodulation and antivirals is inconclusive. 7 8 When presented with a poorly feeding neonate in association with respiratory distress or shock, it is important to consider cardiac causes, especially in the presence of inappropriate persistent tachycardia. The presentation of enteroviral infections can be biphasic. Neonates with initial noncardiacrelated disease Table 1 Demographics, laboratory and cardiac investigations, treatment and outcomes of the eight patients with neonatal enterovirus myocarditis

Collodion membrane covers a heterogeneous group of ichthyoses with disparate outcomes. In this large, prospective birth-cohort study we show that babies with non-syndromic collodion membrane are born in good condition and in 40% the ichthyosis resolves within a year. Our data challenges existing guidelines and supports expectant management.

IMPORTANCE Investigating how the risk of serious illness after SARS-CoV-2 infection in children and adolescents has changed as new variants have emerged is essential to inform public health interventions and clinical guidance. OBJECTIVE To examine risk factors associated with hospitalization for COVID-19 or pediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2 (PIMS-TS) among children and adolescents during the first 2 years of the COVID-19 pandemic and change in risk factors over time. DESIGN, SETTING, AND PARTICIPANTS This population-level analysis of hospitalizations after SARS-CoV-2 infection in England among children and adolescents aged 0 to 17 years was conducted from February 1, 2020, to January 31, 2022. National data on hospital activity were linked with data on SARS-CoV-2 testing, SARS-CoV-2 vaccination, pediatric intensive care unit (PICU) admissions, and mortality. Children and adolescents hospitalized with COVID-19 or PIMS-TS during this time were included. Maternal, elective, and injury-related hospitalizations were excluded. EXPOSURES Previous medical comorbidities, sociodemographic factors, and timing of hospitalization when different SARS-CoV-2 variants (ie, wild type, Alpha, Delta, and Omicron) were dominant in England. MAIN OUTCOMES PICU admission and death within 28 days of hospitalization with COVID-19 or PIMS-TS. RESULTS A total of 10 540 hospitalizations due to COVID-19 and 997 due to PIMS-TS were identified within 1 125 010 emergency hospitalizations for other causes. The number of hospitalizations due to COVID-19 and PIMS-TS per new SARS-CoV-2 infections in England declined during the second year of the COVID-19 pandemic. Among 10 540 hospitalized children and adolescents, 448 (4.3%) required PICU admission due to COVID-19, declining from 162 of 1635 (9.9%) with wild type, 98 of 1616 (6.1%) with Alpha, and 129 of 3789 (3.4%) with Delta to 59 of 3500 (1.7%) with Omicron. Forty-eight children and adolescents died within 28 days of hospitalization due to COVID-19, and no children died of PIMS-TS (PIMS-S data were limited to November 2020 onward). Risk of severe COVID-19 in children and adolescents was associated with medical comorbidities and neurodisability regardless of SARS-CoV-2 variant. Results were similar when children and adolescents with prior SARS-CoV-2 exposure or vaccination were excluded. CONCLUSIONS In this study of data across the first 2 years of the COVID-19 pandemic, risk of severe disease from SARS-CoV-2 infection in children and adolescents in England remained low. Children and adolescents with multiple medical problems, particularly neurodisability, were at increased risk and should be central to public health measures as further variants emerge.

Enteroviruses are a common cause of seasonal child-hood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

Importance:The optimal first-line mode of noninvasive respiratory support for acutely ill children is not known. Objective:To evaluate the noninferiority of high-flow nasal cannula therapy (HFNC) as the first-line mode of noninvasive respiratory support for acute illness, compared with continuous positive airway pressure (CPAP), for time to liberation from all forms of respiratory support. Design, Setting, and Participants:Pragmatic, multicenter, randomized noninferiority clinical trial conducted in 24 pediatric critical care units in the United Kingdom among 600 acutely ill children aged 0 to 15 years who were clinically assessed to require noninvasive respiratory support, recruited between August 2019 and November 2021, with last follow-up completed in March 2022. Interventions:Patients were randomized 1:1 to commence either HFNC at a flow rate based on patient weight (n = 301) or CPAP of 7 to 8 cm H2O (n = 299). Main Outcomes and Measures:The primary outcome was time from randomization to liberation from respiratory support, defined as the start of a 48-hour period during which a participant was free from all forms of respiratory support (invasive or noninvasive), assessed against a noninferiority margin of an adjusted hazard ratio of 0.75. Seven secondary outcomes were assessed, including mortality at critical care unit discharge, intubation within 48 hours, and use of sedation. Results:Of the 600 randomized children, consent was not obtained for 5 (HFNC: 1; CPAP: 4) and respiratory support was not started in 22 (HFNC: 5; CPAP: 17); 573 children (HFNC: 295; CPAP: 278) were included in the primary analysis (median age, 9 months; 226 girls [39%]). The median time to liberation in the HFNC group was 52.9 hours (95% CI, 46.0-60.9 hours) vs 47.9 hours (95% CI, 40.5-55.7 hours) in the CPAP group (absolute difference, 5.0 hours [95% CI -10.1 to 17.4 hours]; adjusted hazard ratio 1.03 [1-sided 97.5% CI, 0.86-∞]). This met the criterion for noninferiority. Of the 7 prespecified secondary outcomes, 3 were significantly lower in the HFNC group: use of sedation (27.7% vs 37%; adjusted odds ratio, 0.59 [95% CI, 0.39-0.88]); mean duration of critical care stay (5 days vs 7.4 days; adjusted mean difference, -3 days [95% CI, -5.1 to -1 days]); and mean duration of acute hospital stay (13.8 days vs 19.5 days; adjusted mean difference, -7.6 days [95% CI, -13.2 to -1.9 days]). The most common adverse event was nasal trauma (HFNC: 6/295 [2.0%]; CPAP: 18/278 [6.5%]). Conclusions and Relevance:Among acutely ill children clinically assessed to require noninvasive respiratory support in a pediatric critical care unit, HFNC compared with CPAP met the criterion for noninferiority for time to liberation from respiratory support. Trial Registration:ISRCTN.org Identifier: ISRCTN60048867.

ABSTRACTBackgroundWe aimed to use individual patient data to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in children and young people (CYP) in hospital.MethodsWe searched Pubmed, European PMC, Medline and Embase for case series and cohort studies that included all CYP admitted to hospital with ≥30 CYP with SARS-CoV-2 or ≥5 CYP with PIMS-TS or MIS-C. Eligible studies contained 1) details of age, sex, ethnicity or co-morbidities, and 2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted grouping of co-morbidities were eligible for narrative review. Authors of eligible studies were approached for individual patient data (IPD). We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).Findings81 studies were included, 57 in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1-4 years, infants had increased odds of admission to critical care (OR 1.63 (95% CI 1.40-1.90)) and death (OR 2.08 (1.57-2.86)). Odds of death were increased amongst CYP over 10 years (10-14 years OR 2.15 (1.54-2.98); >14 years OR 2.15 (1.61-2.88)).Number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a dose-related fashion. For critical care admission odds ratios were: 1 comorbidity 1.49 (1.45-1.53); 2 comorbidities 2.58 (2.41-2.75); ≥3 comorbidities 2.97 (2.04-4.32), and for death: 1 comorbidity 2.15 (1.98-2.34); 2 comorbidities 4.63 (4.54-4.74); ≥3 co-morbidities 4.98 (3.78-6.65). Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91-0.94)) and malignancy (0.85 (0.17-4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities.InterpretationHospitalised CYP at greatest vulnerability of severe disease or death from SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions.FundingRH is in receipt of a funded fellowship from Kidney Research UK. JW is in receipt of a Medical Research Council Fellowship.Putting Research Into ContextEvidence before this studyThe risk factors for severe disease following SARS-CoV-2 infection in adults has been extensively studied and reported, with good evidence that increasing age, non-white ethnicity, male gender and co-morbidities increase the risk. SARS-CoV-2 infection in children and young people (CYP) infrequently results in hospital admission and very rarely causes severe disease and death, making it difficult to discern the impact of a range of potential risk factors for severe disease in the many small to moderate sized published studies. More recent larger publications have aimed to address this question in specific populations but the global experience has not been described. We searched Pubmed, European PMC, Medline and Embase from the 1stJanuary 2020 to 21stMay 2021 for case series and cohort studies that included all CYP admitted to hospital with 30 children with reverse transcriptase-PCR confirmed SARS-CoV-2 or 5 CYP defined as having PIMS-TS or MIS-C. 57 studies met the eligibility criteria for meta-analysis.Added value of this studyTo our knowledge, this is the first meta-analysis to use individual patient data to compare the odds and risk of critical care admission and death in CYP with COVID-19 and PIMS-TS. We find that the odds of severe disease in hospitalised children is increased in those with multiple co-morbidities, cardiac and neurological co-morbidities and those who are obese. However, the additional risk compared to children without co-morbidity is small.Implications of all the available evidenceSevere COVID-19 and PIMS-TS, whilst rare, can occur in CYP. We have identified pre-existing risk factors for severe disease after SARS-CoV-2 and recommend that those with co-orbidities which place them in the highest risk groups are prioritised for vaccination.

OBJECTIVES:To explore the experiences of clinical leads in paediatric critical care units (PCCUs) in England and Wales during the reorganisation of services in the initial surge of the SARS-CoV-2 pandemic and to learn lessons for future surges and service planning.METHODS:A qualitative study design using semistructured interviews via virtual conferencing was conducted with consultant clinical leads and lead nurses covering 21 PCCUs. Interviews were conducted over a period of 2 weeks, 2 months after the initial SARS-CoV-2 surge. Interview notes underwent thematic analysis.RESULTS:Thematic analysis revealed six themes: leadership, management and planning; communication; workforce development and training; innovation; workforce experience; and infection prevention and control. Leadership was facilitated through clinician-led local autonomy for decision-making and services were better delivered when the workforce was empowered to be flexible in their response. Communication was preferred through collaborative management structures. Further lessons include recognising workforce competencies in surge preparations, the use of virtual technology in facilitating training and meetings, the importance of supporting the well-being of the workforce and the secondary consequences of personal protective equipment use.CONCLUSIONS:During the 2020 SARS-CoV-2 pandemic, an agile response to a rapidly changing situation was enabled through effective clinical leadership and an adaptive workforce. Open systems of communication across senior clinical and management teams facilitated service planning. Support for all members of the workforce through implementation of appropriate and innovative education and well-being solutions was vital in sustaining resilience. This learning supports planning for future surge capacity across paediatric critical care locally and nationally.

Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective interventions. To address this question, we used data for all hospitalizations in England among 0–17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020–2021); hospitalizations due to all other non-traumatic causes in 2020–2021; hospitalizations due to all non-traumatic causes in 2019–2020; and hospitalizations due to influenza in 2019–2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15–17 year olds compared to 1–4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies. The risk of intensive care unit admission among children with COVID-19 or its sequelae is affected by age, ethnicity and comorbidities. Understanding these modifiers might help identify at-risk children and guide interventions.