Developing survey weights to ensure representativeness in a national, matched cohort study: results from the Children and young people with Long Covid (CLoCk) study. (preprint)

Background: Findings from studies assessing Long Covid in children and young people (CYP) need to be viewed in light of their methodological limitations. For example, if non-response and/or attrition over time systematically differ by sub-groups of CYP, findings could be biased and generalisation limited. The present study aimed to (i) construct survey weights for the Children and young people with Long Covid (CLoCk) study, and (ii) apply them to published CLoCk findings showing the prevalence of shortness of breath and tiredness increased over time from baseline to 12-months post-baseline in both SARS-CoV-2 Positive and Negative CYP. Methods: Logistic regression was used to compute the probability of (i) Responding given envisioned to take part, (ii) Responding timely given responded, and (iii) (Re)infection given timely response. Response, timely response and (re)infection weights were generated as the reciprocal of the corresponding probability, with an overall ‘envisioned population’ survey weight derived as the product of these weights. Survey weights were trimmed, and an interactive tool developed to re-calibrate target population survey weights to the general population using data from the 2021 UK Census. Results: Flexible survey weights for the CLoCk study were successfully developed. In the illustrative example re-weighted results (when accounting for selection in response, attrition, and (re)infection) were consistent with published findings. Conclusions: Flexible survey weights to address potential bias and selection issues were created for and used in the CLoCk study. Previously reported prospective findings from CLoCk are generalisable to the wider population of CYP in England. This study highlights the importance of considering selection into a sample and attrition over time when considering generalisability of findings.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data (preprint)

Background Deaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive. Methods During the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings 3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99.995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children. Interpretation SARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination.

Deaths in Children and Young People in England following SARS-CoV-2 infection during the first pandemic year: a national study using linked mandatory child death reporting data (preprint)

BackgroundDeaths in children and young people (CYP) following SARS-CoV-2 infection are rare. Quantifying the risk of mortality is challenging because of high relative prevalence of asymptomatic and non-specific disease manifestations. Therefore, it is important to differentiate between CYP who have died of SARS-CoV-2 and those who have died of an alternative disease process but coincidentally tested positive.MethodsDuring the pandemic, the mandatory National Child Mortality Database (NCMD) was linked to Public Health England (PHE) testing data to identify CYP (<18 years) who died with a positive SARS-CoV-2 test. A clinical review of all deaths from March 2020 to February 2021 was undertaken to differentiate between those who died of SARS-CoV-2 infection and those who died of an alternative cause but coincidentally tested positive. Then, using linkage to national hospital admission data, demographic and comorbidity details of CYP who died of SARS-CoV-2 were compared to all other deaths. Absolute risk of death was estimated where denominator data were available. Findings3105 CYP died from all causes during the first pandemic year in England. 61 of these deaths occurred in CYP who tested positive for SARS-CoV-2. 25 CYP died of SARS-CoV-2 infection; 22 from acute infection and three from PIMS-TS. 99·995% of CYP with a positive SARS-CoV-2 test survived. The 25 CYP who died of SARS-CoV-2 equates to a mortality rate of 2/million for the 12,023,568 CYP living in England. CYP >10 years, of Asian and Black ethnic backgrounds, and with comorbidities were over-represented compared to other children.InterpretationSARS-CoV-2 is very rarely fatal in CYP, even among those with underlying comorbidities. These findings are important to guide families, clinicians and policy makers about future shielding and vaccination.

Risk factors for intensive care admission and death amongst children and young people admitted to hospital with COVID-19 and PIMS-TS in England during the first pandemic year (preprint)

Identifying which children and young people (CYP) are vulnerable to severe disease following SARS-CoV-2 is important to guide shielding and vaccination policy. Methods We used data for all inpatient hospital admissions in England in CYP aged 0-17 between March 1st 2015 to Feb 28th 2021, linked to paediatric intensive care unit (PICU) admission, and SARS-CoV-2 PCR testing, and deaths. We calculated odds ratios and predicted probability of PICU admission using generalized estimation equations, and compared these between COVID-19, PIMS-TS, other admissions in 2020/21, all admissions in 2019/20, and admissions due to influenza in 20219/20. Findings There were 6,338 COVID-19 hospitalisations, 259 PICU admissions and 8 deaths as well as 712 PIMS-TS hospitalisations, 312 PICU admissions and <5 deaths. Odds of PICU admission were increased amongst neonates and decreased amongst 15-17 compared with 1-4 year olds with COVID-19, increased in older CYP and females with PIMS-TS, and increased for Black compared with White ethnicity for both conditions. Odds of PICU admission with COVID-19 were increased for CYP with any comorbidity and were highest for CYP with multiple medical problems. Comorbidities associated with PICU admission among COVID-19 patients were similar to overall PICU admissions in 2019/20 and to influenza PICU admissions in 2019/20, but with higher odds. Interpreting associations with comorbidities within PIMS-TS was complex due to the multisystem nature of the disease. Interpretation CYP were at very low risk of severe disease and death from COVID-19 or PIMS-TS. Patterns of vulnerability for severe COVID-19 appear to magnify background risk factors for serious illness in CYP.

Recent and forecast post-COVID trends in hospital activity in England amongst 0 to 24 year olds: analyses using routine hospital administrative data (preprint)

BackgroundIncreasing hospital use in the past decade has placed considerable strain on children and young peoples (CYP) health services in England. Greater integration of healthcare may reduce these increases. We projected CYP healthcare activity out to 2040 and examined the potential impact of integrated care systems on projected activity. MethodsWe used routine administrative data (Hospital Episode Statistics (HES)) on emergency department (ED) attendances, emergency admissions and outpatient (OP) attendances for England by age-group for 0-24 year olds from 2007 to 2017. Bayesian projections of future activity used projected population and ethnicity and future child poverty rates. Cause data were used to identify ambulatory-care-sensitive-conditions (ACSC). FindingsED attendances, emergency admissions and OP attendances increased in all age groups from 2007 to 2017. ED and OP attendances increased 60-80% amongst children under 10 years. ACSC and neonatal causes drove the majority of increases in emergency admissions. Activity was projected to increase by 2040 by 50-145% for ED attendances, 20-125% for OP attendances and 4-58% for total admissions. Scenarios of increasing or decreasing child poverty resulted in small changes to forecast activity. Scenarios in which 50% of ACSC were seen outside hospital in integrated care reduced estimated activity in 2040 by 21.2-25.9% for admissions and 23.5-30.1% for ED attendances across poverty scenarios amongst infants. InterpretationThe rapid increases in CYP healthcare activity seen in the past decade may continue for the next decade given projected changes in population and child poverty, unless some of the drivers of increased activity are addressed. Contrary to these pessimistic scenarios, our findings suggest that development of integrated care for CYP at scale in England has the potential to dramatically reduce or even reverse these forecast increases FundingNil funding obtained. Research in contextO_ST_ABSEvidence before this studyC_ST_ABSThere has been marked increases in hospital use (inpatient, outpatient and emergency department (ED)) by children and young people (CYP). Search of the PubMed database using the search terms: ((((("child"[MeSH Major Topic]) OR ("adolescent"[MeSH Major Topic])) OR ("infant"[MeSH Major Topic]))) AND ((healthcare use[Text Word])) OR (emergency admission[Text Word])) AND (united kingdom[Text Word]). Drivers of increased activity include population growth and sociodemographic factors, help-seeking behaviour, growth in medical knowledge and capability, and by factors within the health system. Additional factors in child health include increased survival of premature neonates and those with congenital conditions and rising parental expectations of modern medicine. Previous studies have shown that ambulatory-care-sensitive-conditions (ACSC) are responsible for much of the increase in CYP emergency activity in England and Scotland. Added value of this studyThis is the first study to use existing data to project possible future scenarios for CYP healthcare activity out to 2030 and 2040 in any country. Our future scenarios are based upon authoritative projections for population, ethnic diversity and child poverty in England and allow us to estimate the potential impact of integrated care scenarios in which ACSC are treated outside hospital. We show that future projected CYP activity is very high if mitigations such as integrated care are not instituted in England. Implications of all the available evidenceHealthcare activity has grown dramatically over the last decade in CYP, largely due to ACSC and the consequences of premature delivery. Projections to 2040 suggest that similar increases are likely over the next 2 decades without action to reduce child poverty and implementation of integrated care at scale in the NHS.

Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents (preprint)

Objective To undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years? Design Narrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020. Setting All settings, including hospitalised and community settings. Patients CYP under age 20 years with laboratory-proven COVID-19. Study review, data extraction and quality Potentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers. Main outcome measures Prevalence of symptoms and signs of COVID-19 Results 1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion who were asymptomatic ranged from 14.6 to 42%. Fever and cough were the commonest symptoms; proportions with fever ranged from 46 to 64.2% and with cough from 32 to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting are infrequent, occurring in less than 10-20%. Conclusions Fever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP.