The post-COVID condition involves persistent symptoms, following SARS-CoV-2 infection, that impact on multiple body systems and affect functioning. In June 2021, NHS England established specialist paediatric post-COVID (PC) hubs to provide support. However, data on the use and effectiveness of these hubs remain limited. NHS England data were employed to analyse referral patterns, including total referrals, rejections, waiting times, and assessments. Sex, age and ethnicity were also examined. Outcome data from a subset of the hubs were analysed. Between 2 January 2022 and 31 October 2023, 1 374 referrals were received, with 1 123 assessments conducted. The median duration between referral and initial assessment was 49–55 days. Most patients were female (59%), aged 12–15 (55%) and White (80%). Sparse outcome data suggested improvements in functioning, wellbeing, fatigue, and school attendance. While specialist paediatric PC hubs provide critical support, limitations in outcome data and data quality constrain definitive conclusions about their use and effectiveness, highlighting the need for improved reporting systems to better inform service planning.

BACKGROUND:Despite having marginal beneficial effects, antibiotics are routinely prescribed in adults with acute sinusitis. Alternative interventions for this common condition are urgently needed. AIM:To assess the feasibility and acceptability of saline nasal irrigation for acute sinusitis. DESIGN & SETTING:Randomised controlled pilot trial with nested process evaluation in 24 English general practices between October 2019 and May 2021. METHOD:Participants were randomised to advice to high-volume hypertonic saline nasal irrigation with a delayed antibiotic prescription or usual care. Feasibility outcomes included recruitment and follow-up rates, adherence, and acceptability of the intervention. RESULTS:Of those invited, n = 81/107 (76%) consented and were randomised (42 intervention, 39 usual care). Two participants were excluded owing to ineligibility. Antibiotic prescribing strategies were recorded at baseline for n = 79/79 (100%), with no or delayed antibiotics prescribed in 60% (n = 24/40) of the saline group versus 38% (n = 15/39) of the usual care group. At follow-up, 80% (n = 63/79) of participants recorded whether they consumed antibiotics or not. Among those from the intervention group who returned a symptom diary, 96% (n = 22/23) and 65% (n = 15/23) reported using saline nasal irrigation during the first and second week, respectively. Semi-structured interviews with 16 participants revealed that most were positive about trial participation and viewed saline nasal irrigation as acceptable, noting it as an alternative to antibiotics. CONCLUSION:Saline nasal irrigation is deemed acceptable for adults with acute sinusitis and a trial of such intervention is feasible. A large trial is warranted to assess the effectiveness of this intervention for this common condition.

Abstract Background Predicting which children and young people (CYP) are at the highest risk of developing post-COVID-19 condition (PCC) could improve care pathways. We aim to develop and validate prediction models for persistent PCC up to 24 months post-infection in CYP. Methods CYP who were PCR-positive between September 2020 and March 2021, with follow-up data up to 24-months post-infection, were analysed. Persistent PCC was defined in two ways, as PCC at (a) 3, 6, 12 and 24 months post-infection (N = 943) or (b) 6, 12 and 24 months post-infection (N = 2373). Prediction models were developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping; the final model was adjusted for overfitting. Results While 24.7% (233/943) of CYP met the PCC definition 3 months post-infection, only 7.2% (68/943) continued to meet the PCC definition at all three subsequent timepoints, i.e. at 6, 12 and 24 months. The final models predicting risk of persistent PCC (at 3, 6, 12 and 24 months and at 6, 12 and 24 months) contained sex (female), history of asthma, allergy problems, learning difficulties at school and family history of ongoing COVID-19 problems, with additional variables (e.g. older age at infection and region of residence) in the model predicting PCC at 6, 12 and 24 months. Internal validation showed minimal overfitting of models with good calibration and discrimination measures (optimism-adjusted calibration slope: 1.064–1.142; C-statistic: 0.724–0.755). Conclusions To our knowledge, these are the only prediction models estimating the risk of CYP persistently meeting the PCC definition up to 24 months post-infection. The models could be used to triage CYP after infection. CYP with factors predicting longer-term symptomology, may benefit from earlier support.

AbstractBackgroundChildhood, teenage and young adult (CTYA, 0-24 years) cancers are rare and diverse, making timely diagnosis challenging. Studies based on adult cancers suggest that the development and integration of clinical decision tools in primary care aid earlier cancer detection, yet, these have not been explored for CTYA cancers.AimTo develop and validate a primary care-based risk prediction tool to identify CTYA who are at increased risk of cancer.Methods and analysisUsing the QResearch Database, a nationally representative primary care database, we will generate an open cohort of children, teenagers and young adults (0-24 years) who were registered with a GP between 1stJanuary 1998 and 31stDecember 2019. CTYA will be followed up from the date at which the first cancer-relevant symptom is recorded in the records (index date) until the date of cancer diagnosis/6-months, whichever comes first. Candidate variables will include symptoms, signs, blood test results and demographic factors. Model derivation will include two approaches, Cox regression and logistic regression. Apparent performance of the derived model will be explored and subsequently internally-externally cross-validated to investigate performance heterogeneity and geographical transportability.

Background Coeliac Disease (CD) often has its onset in childhood and affects 1% of the population. This review aimed to identify important predictive factors for coeliac disease in children and young people which could help GPs decide when to offer testing. Methods We searched MEDLINE, Embase and Cochrane Library to April 2024. Included studies were observational or randomized trials reporting the risk of CD when exposed to predictive factor(s) in people ≤25 years of age. Genetic factors were excluded. Risk of Bias was assessed using the Newcastle-Ottawa Scale. Random effects meta-analysis was performed for factors reported in ≥5 studies to calculate pooled odds ratios (OR) or standardized mean differences (SMD). Results Of 11,623 unique abstracts, 183 were included reporting on 140+ potentially associated factors. Meta-analyses of 28 factors found 14 significant associations with CD diagnosis: having type 1 diabetes (OR 8.70), having a first degree relative with coeliac disease (OR 5.19), being of white ethnicity (OR 2.56), having thyroid disease (OR 2.16), being female (OR 1.53), more frequent gastroenteritis in early childhood (OR 1.48), having frequent respiratory infections in early childhood (OR 1.47), more gluten ingestion in early life (OR 1.25), having more infections in early life (OR 1.22), antibiotic use in early childhood (OR 1.21), being born in the summer (OR 1.09), breastfeeding (OR 0.79) older age at diagnosis of type 1 diabetes (OR 0.64), and heavier weight (SMD -0.21). The final three were associated with lower risk of CD diagnosis. Discussion This is the first systematic review and meta-analysis of predictive factors for CD in children. Amongst the 14 factors we identified that were significant, three were potentially modifiable: breast feeding, antibiotic use and amount of gluten ingestion in early childhood. This work could inform the development of clinical support tools to facilitate the early diagnosis of CD.

BACKGROUND:Post-COVID Condition (PCC), also known as 'Long COVID,' refers to persistent symptoms following a coronavirus 2 (SARS-CoV-2) infection. The prevalence of PCC in children and adolescents varies, impacting multiple body systems and affecting daily functioning. Specialised paediatric hubs were established in England to address the needs of young individuals with PCC. Additional local services also emerged, yet patients report challenges accessing services. To better understand the landscape of paediatric PCC services, we used a novel methodology using a web-based systematic search. METHODS:A web-based search was conducted in July 2023 using DEVONagent Pro. Search terms related to Long COVID and Pediatrics in England. Eligible sources providing information on PCC services for children and young people were included. A supplementary manual search and NHS England Post-COVID Network were also consulted. Data extraction included service location, characteristics, and referral pathways. Population estimates were derived from UK Census data. RESULTS:Among 342 identified records, 27 services met eligibility criteria, distributed unevenly across regions. Specialised hubs covered 13 locations, while additional services were concentrated in the South of England and London. Services varied in team composition, age range treated, and support offered. A lack of standardised approaches for paediatric PCC was evident. DISCUSSION:We used a novel methodology for systematically mapping online resources, providing valuable insights into service accessibility and aiding the identification of potential gaps. We observed geographical disparities in access to paediatric PCC services and the absence of standardised approaches in managing symptoms. Given the challenges faced by young individuals seeking support for their PCC the need for equitable and standardised care became apparent. The study contributes to closing the research-practice gap and calls for further research to identify effective treatments for paediatric PCC, acknowledging the diversity of reported symptoms and the importance of tailored approaches.

AbstractThe risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1–42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0–5) and 5 (95%CI 3–6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0–23) hospitalisations with epilepsy and 4 (95%CI 0–6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.

Abstract Background Some children and young people (CYP) infected with SARS-COV-2 experience impairing symptoms post-infection, known as post-COVID-19 condition (PCC). Using data from the National Long COVID in Children and Young People (CloCk) study, we report symptoms and their impact up to 24-months post-infection. Methods CloCk is a cohort of CYP in England aged 11-to-17-years when they had a SARS-CoV-2 PCR-test (between September 2020 and March 2021). Of 31,012 eligible CYP 24-months post-PCR test, 12,632 participated (response = 40.7%). CYP were grouped by infection status: ‘initial test-negatives; no subsequent positive-test’ (NN); ‘initial test-negatives; subsequent positive-test’ (NP); ‘initial test-positives; no reported re-infection’ (PN); and ‘initial test-positives; reported re-infection’ (PP). The Delphi research definition of PCC in CYP was operationalised; symptom severity/impact and validated scales (e.g., Chalder Fatigue Scale) were recorded. We examine symptom profiles 24-month post-index-test by infection status. Results 7.2% of CYP consistently fulfil the PCC definition at 3-, 6-, 12- and 24-months. These CYPs have a median of 5-to-6 symptoms at each time-point. Between 20% and 25% of all infection status groups report 3+ symptoms 24-months post-testing; 10–25% experience 5+ symptoms. The reinfected group has more symptoms than the other positive groups; the NN group has the lowest symptom burden (p < 0.001). PCC is more common in older CYPs and in the most deprived. Symptom severity/impact is higher in those fulfilling the PCC definition. Conclusions The discrepancy in the proportion of CYP fulfilling the Delphi PCC definition at 24-months and those consistently fulfilling the definition across time, highlights the importance of longitudinal studies and the need to consider clinical impairment and range of symptoms.

Background:Antimicrobial resistance is a global health threat. Antibiotics are commonly prescribed for children with uncomplicated lower respiratory tract infections, but there is little randomised evidence to support the effectiveness of antibiotics in treating these infections, either overall or relating to key clinical subgroups in which antibiotic prescribing is common (chest signs; fever; physician rating of unwell; sputum/rattly chest; shortness of breath). Objectives:To estimate the clinical effectiveness and cost-effectiveness of amoxicillin for uncomplicated lower respiratory tract infections in children both overall and in clinical subgroups. Design:Placebo-controlled trial with qualitative, observational and cost-effectiveness studies. Setting:UK general practices. Participants:Children aged 1-12 years with acute uncomplicated lower respiratory tract infections. Outcomes:The primary outcome was the duration in days of symptoms rated moderately bad or worse (measured using a validated diary). Secondary outcomes were symptom severity on days 2-4 (0 = no problem to 6 = as bad as it could be); symptom duration until very little/no problem; reconsultations for new or worsening symptoms; complications; side effects; and resource use. Methods:Children were randomised to receive 50 mg/kg/day of oral amoxicillin in divided doses for 7 days, or placebo using pre-prepared packs, using computer-generated random numbers by an independent statistician. Children who were not randomised could participate in a parallel observational study. Semistructured telephone interviews explored the views of 16 parents and 14 clinicians, and the data were analysed using thematic analysis. Throat swabs were analysed using multiplex polymerase chain reaction. Results:A total of 432 children were randomised (antibiotics, n = 221; placebo, n = 211). The primary analysis imputed missing data for 115 children. The duration of moderately bad symptoms was similar in the antibiotic and placebo groups overall (median of 5 and 6 days, respectively; hazard ratio 1.13, 95% confidence interval 0.90 to 1.42), with similar results for subgroups, and when including antibiotic prescription data from the 326 children in the observational study. Reconsultations for new or worsening symptoms (29.7% and 38.2%, respectively; risk ratio 0.80, 95% confidence interval 0.58 to 1.05), illness progression requiring hospital assessment or admission (2.4% vs. 2.0%) and side effects (38% vs. 34%) were similar in the two groups. Complete-case (n = 317) and per-protocol (n = 185) analyses were similar, and the presence of bacteria did not mediate antibiotic effectiveness. NHS costs per child were slightly higher (antibiotics, £29; placebo, £26), with no difference in non-NHS costs (antibiotics, £33; placebo, £33). A model predicting complications (with seven variables: baseline severity, difference in respiratory rate from normal for age, duration of prior illness, oxygen saturation, sputum/rattly chest, passing urine less often, and diarrhoea) had good discrimination (bootstrapped area under the receiver operator curve 0.83) and calibration. Parents found it difficult to interpret symptoms and signs, used the sounds of the child's cough to judge the severity of illness, and commonly consulted to receive a clinical examination and reassurance. Parents acknowledged that antibiotics should be used only when 'necessary', and clinicians noted a reduction in parents' expectations for antibiotics. Limitations:The study was underpowered to detect small benefits in key subgroups. Conclusion:Amoxicillin for uncomplicated lower respiratory tract infections in children is unlikely to be clinically effective or to reduce health or societal costs. Parents need better access to information, as well as clear communication about the self-management of their child's illness and safety-netting. Future work:The data can be incorporated in the Cochrane review and individual patient data meta-analysis. Trial registration:This trial is registered as ISRCTN79914298. Funding:This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 9. See the NIHR Journals Library website for further project information.

Background Influenza and influenza-like illness place significant burden on the NHS. Children with underlying health conditions are vulnerable to developing bacterial complications. Objective To strengthen the evidence base underlying antibiotic use in at-risk children with influenza-like illness. Design This programme comprised five separate work packages. Work package A investigated published and unpublished data from previously published literature and work package B explored attitudes of parents and general practitioners to influenza-like illness and antibiotics in at-risk children. This was followed by a clinical trial to assess the effectiveness of early co-amoxiclav (Augmentin ® , GlaxoSmithKline UK) use at reducing reconsultation due to clinical deterioration (work package C), a nested sub-study to examine bacterial carriage indicators of antibiotic resistance (work package D) and a within-trial economic evaluation and clinical risk prediction analysis (work package E). Setting Interviews were conducted by telephone with general practitioners across the UK and parents/guardians in England (work package B). We conducted the clinical trial (work package C and nested work packages D and E) in general practices and ambulatory care services in England and Wales. Participants General practitioners and parents/guardians of at-risk children who previously had influenza-like illness participated in work package B. At-risk children with influenza-like illness aged 6 months to 12 years participated in work packages C and E and optionally in work package D. Interventions The intervention for the clinical trial was a 5-day course of co-amoxiclav 400/57 with dosing regimens based on British National Formulary guidance. Main outcome measures Hospital admission (work package A); findings from semi-structured interviews with patients and health-care professionals (work package B); proportion of patients who reconsulted owing to clinical deterioration (work package C); respiratory bacterial carriage and antibiotic resistance of potentially pathogenic respiratory tract bacteria at 3, 6, 9 and 12 months (work package D); and risk factors for reconsultation owing to clinical deterioration, quality of life (EuroQol-5 Dimensions, three-level youth version), symptoms (Canadian Acute Respiratory Infection and Flu Scale), health-care use and costs (work package E). Review methods For work package A, we searched the MEDLINE, MEDLINE In-Process, EMBASE, Science Citation Index and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases until 3 April 2013 with no language restrictions and requested unpublished data from authors of studies which had collected but not published relevant data. We included studies involving children up to 18 years of age with influenza or influenza-like illness from primary or ambulatory care settings. We used univariable meta-analysis methods to calculate odds ratios with 95% confidence intervals for individual risk factors. We reported our systematic review according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2009 statement. Results Work package A analysed data from 28 articles reporting data from 27 studies. Neurological disorders, sickle cell disease, immunosuppression, diabetes and an age of <2 years were risk factors for hospital admission. Work package B interviewed 41 general practitioners and found that decision-making in at-risk children with influenza-like illness varies considerably. Parents/guardians were interviewed for work package B and spoke of how quickly their at-risk child could deteriorate. They were supportive of antibiotic use while being aware of antibiotic resistance. The trial (work package C) recruited 271 at-risk children. Primary outcome data were available for 265 children. There was no evidence of benefit from treatment with co-amoxiclav versus placebo (adjusted risk ratio 1.16, 95% confidence interval 0.75 to 1.80). Work package D collected 285 additional throat swabs over 12 months. At 3 months, the proportion of Haemophilus influenzae isolates was greater in the placebo than co-amoxiclav group (29% vs. 18%). No association was found between antibiotic resistance and early co-amoxiclav use. No clinical features were significantly associated with risk of reconsultation due to clinical deterioration except respiratory rate (coefficient 0.046, 95% confidence interval 0.010 to 0.081). Work package E found no evidence that early co-amoxiclav treatment improves quality of life or reduces health-care use and costs. Total costs per patient were highly skewed in both groups (co-amoxiclav: median £4, range £4–5258; placebo: median £0, range £0–5177). Limitations We were not able to recruit our target sample size for the trial. This impacted the data available for microbiology, health economics and risk reduction score analyses. Conclusions Our results do not support early antibiotic prescribing to at-risk children with influenza-like illness during influenza season. Future work Further research is required to determine if antibiotic treatment would be beneficial during periods of higher influenza activity such as influenza pandemics, to identify children who would gain most clinical benefit and to better understand families’ reconsultation decisions. Trial registration This trial is registered as ISRCTN70714783 and EudraCT 2013-002822-21. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Programme Grants for Applied Research and will be published in full in Programme Grants for Applied Research ; Vol. 11, No. 1. See the NIHR Journals Library website for further project information.

Background The COVID-19 pandemic has affected millions of people globally with major health, social and economic consequences, prompting development of vaccines for use in the general population. However, vaccination uptake is lower in some groups, including in pregnant women, because of concerns regarding vaccine safety. There is evidence of increased risk of adverse pregnancy and neonatal outcomes associated with SARS-CoV-2 infection, but fear of vaccine-associated adverse events on the baby both in short and longer term is one of the main drivers of low uptake for this group. Other vaccines commonly used in pregnancy include influenza and pertussis. These both have reportedly higher uptake compared with COVID-19 vaccination, which may be because they are perceived to be safer. In this study, we will undertake an independent evaluation of the uptake, effectiveness and safety of COVID-19 vaccinations in pregnant women using the QResearch primary care database in England. Objectives 1. To determine COVID-19 vaccine uptake in pregnant women compared to uptake of influenza and pertussis vaccinations. 2. To estimate COVID-19 vaccine effectiveness in pregnant women by evaluating the risk of severe COVID-19 outcomes following vaccination. 3. To assess the safety of COVID-19 vaccination in pregnancy by evaluating the risks of adverse pregnancy and perinatal outcomes and adverse events of special interest for vaccine safety after COVID-19 vaccination compared with influenza and pertussis vaccinations. Methods This population-based study uses the QResearch® database of primary health care records, linked to individual-level data on hospital admissions, mortality, COVID-19 vaccination, SARS-CoV-2 testing data and congenital anomalies. We will include women aged 16 to 49 years with at least one pregnancy during the study period of 30th December 2020 to the latest date available. Babies born during the study period will be identified and linked to the mother’s record, where possible. We will describe vaccine uptake in pregnant women by trimester and population subgroups defined by demographics and other characteristics. Cox proportional hazards multivariable regression will be used to identify factors associated with vaccine uptake. The effectiveness of COVID-19 vaccines in pregnant women will be assessed using a nested matched case-control design to assess hospitalisation, intensive care admission and death with COVID-19. Cases who had the outcome will be matched with up to 10 controls who did not have the outcome on that date by age, calendar date and trimester of pregnancy using incidence density sampling for the occurrence of each outcome after each vaccine dose compared with unvaccinated individuals. For the safety analysis, we will we use logistic regression analyses to determine unadjusted and adjusted odds ratios for the occurrence of maternal (e.g. miscarriage, ectopic pregnancy and gestational diabetes) and perinatal outcomes (e.g. stillbirth, small for gestational age and congenital anomalies) by vaccination status compared to unvaccinated individuals. For the adverse events of special interest for vaccine safety (e.g. venous thromboembolism, myocarditis and Guillain Barre syndrome), we will use time varying Royston-Palmar regression analyses to determine unadjusted and adjusted hazard ratios for the occurrence of each outcome by vaccination status to unvaccinated individuals. Ethics and dissemination QResearch is a Research Ethics Approved Research Database with ongoing approval from the East Midlands Multi-Centre Research Ethics Committee (Ref: 18/EM/0400). This study was approved by the QResearch Scientific Committee on 9th June 2022. This research protocol has been developed with support from a patient and public involvement panel, who will continue to provide input throughout the duration of the study. Research findings will be submitted to pre-print servers such as MedRxIv, academic publication and disseminated more broadly through media releases and community groups and conference presentations. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by NIHR School for Primary Care Research ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: QResearch obtained full approval from the Trent Multi-Centre Research Ethics Committee [Ref: 03/4/021]. Approval is now confirmed yearly from the East Midlands - Derby Research Ethics Committee. In 2018, an updated application was approved [Ref: 18/EM/0400] in readiness for the transfer of QResearch to the University of Oxford. All previous approval letters can be found in the Downloads section. Research studies which utilise QResearch data need to obtain approval from the QResearch Scientific Committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data produced in the present work are contained in the manuscript

Background We describe post-COVID symptomatology in a non-hospitalised, national sample of adolescents aged 11-17 years with PCR-confirmed SARS-CoV-2 infection compared with matched adolescents with negative PCR status. Methods In this national cohort study, adolescents aged 11-17 years from the Public Health England database who tested positive for SARS-CoV-2 between January and March, 2021, were matched by month of test, age, sex, and geographical region to adolescents who tested negative. 3 months after testing, a subsample of adolescents were contacted to complete a detailed questionnaire, which collected data on demographics and their physical and mental health at the time of PCR testing (retrospectively) and at the time of completing the questionnaire (prospectively). We compared symptoms between the test-postive and test-negative groups, and used latent class analysis to assess whether and how physical symptoms at baseline and at 3 months clustered among participants. This study is registered with the ISRCTN registry (ISRCTN 34804192). Findings 23 048 adolescents who tested positive and 27 798 adolescents who tested negative between Jan 1, 2021, and March 31, 2021, were contacted, and 6804 adolescents (3065 who tested positive and 3739 who tested negative) completed the questionnaire (response rate 13.4%). At PCR testing, 1084 (35.4%) who tested positive and 309 (8.3%) who tested negative were symptomatic and 936 (30.5%) from the test-positive group and 231 (6.2%) from the test-negative group had three or more symptoms. 3 months after testing, 2038 (66.5%) who tested positive and 1993 (53.3%) who tested negative had any symptoms, and 928 (30.3%) from the test-positive group and 603 (16.2%) from the test-negative group had three or more symptoms. At 3 months after testing, the most common symptoms among the test-positive group were tiredness (1196 [39.0%]), headache (710 [23.2%]), and shortness of breath (717 [23.4%]), and among the test-negative group were tiredness (911 [24.4%]), headache (530 [14.2%]), and other (unspecified; 590 [15.8%]). Latent class analysis identified two classes, characterised by few or multiple symptoms. The estimated probability of being in the multiple symptom class was 29.6% (95% CI 27.4-31.7) for the test-positive group and 19.3% (17.7-21.0) for the test-negative group (risk ratio 1.53; 95% CI 1.35-1.70). The multiple symptoms class was more frequent among those with positive PCR results than negative results, in girls than boys, in adolescents aged 15-17 years than those aged 11-14 years, and in those with lower pretest physical and mental health. Interpretation Adolescents who tested positive for SARS-CoV-2 had similar symptoms to those who tested negative, but had a higher prevalence of single and, particularly, multiple symptoms at the time of PCR testing and 3 months later. Clinicians should consider multiple symptoms that affect functioning and recognise different clusters of symptoms. The multiple and varied symptoms show that a multicomponent intervention will be required, and that mental and physical health symptoms occur concurrently, reflecting their close relationship. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.

OBJECTIVE:To investigate childhood, teenage and young adult cancer diagnostic pathways during the first wave of the COVID-19 pandemic in England. DESIGN:Population-based cohort study. SETTING AND PARTICIPANTS:QResearch, a nationally representative primary care database, linked to hospital admission, mortality and cancer registry data, was used to identify childhood, teenage and young adult cancers (0-24 years) diagnosed between 1 January 2017 and 15 August 2020. MAIN OUTCOMES:Main outcomes of interest were: (1) number of incident cancer diagnoses per month, (2) diagnostic, treatment time intervals and (3) cancer-related intensive care admissions. RESULTS:2607 childhood, teenage and young adult cancers were diagnosed from 1 January 2017 to 15 August 2020; 380 were diagnosed during the pandemic period. Overall, 17% (95% CI -28.0% to -4.0%) reduction in the incidence rate ratio of cancers was observed during the pandemic. Specific decreases were seen for central nervous system tumour (-38% (95% CI -52% to -21%)) and lymphoma (-28% (95% CI -45% to -5%)) diagnoses. Additionally, childhood cancers diagnosed during the pandemic were significantly more likely to have intensive care admissions (adjusted OR 2.2 (95% CI 1.33 to 3.47)). Median time-to-diagnosis did not significantly differ across periods (+4.5 days (95% CI -20.5 to +29.5)), while median time-to-treatment was shorter during the pandemic (-0.7 days (95% CI -1.1 to -0.3)). CONCLUSIONS:Collectively, our findings of a significant reduction in cancer diagnoses and increase in intensive care admissions provide initial insight into the changes that occurred to childhood, teenage and young adult cancer diagnostic pathways during the first wave of the pandemic.

Background: Myocarditis is more common after severe acute respiratory syndrome coronavirus 2 infection than after COVID-19 vaccination, but the risks in younger people and after sequential vaccine doses are less certain. Methods: A self-controlled case series study of people ages 13 years or older vaccinated for COVID-19 in England between December 1, 2020, and December 15, 2021, evaluated the association between vaccination and myocarditis, stratified by age and sex. The incidence rate ratio and excess number of hospital admissions or deaths from myocarditis per million people were estimated for the 1 to 28 days after sequential doses of adenovirus (ChAdOx1) or mRNA-based (BNT162b2, mRNA-1273) vaccines, or after a positive SARS-CoV-2 test. Results: In 42 842 345 people receiving at least 1 dose of vaccine, 21 242 629 received 3 doses, and 5 934 153 had SARS-CoV-2 infection before or after vaccination. Myocarditis occurred in 2861 (0.007%) people, with 617 events 1 to 28 days after vaccination. Risk of myocarditis was increased in the 1 to 28 days after a first dose of ChAdOx1 (incidence rate ratio, 1.33 [95% CI, 1.09–1.62]) and a first, second, and booster dose of BNT162b2 (1.52 [95% CI, 1.24–1.85]; 1.57 [95% CI, 1.28–1.92], and 1.72 [95% CI, 1.33–2.22], respectively) but was lower than the risks after a positive SARS-CoV-2 test before or after vaccination (11.14 [95% CI, 8.64–14.36] and 5.97 [95% CI, 4.54–7.87], respectively). The risk of myocarditis was higher 1 to 28 days after a second dose of mRNA-1273 (11.76 [95% CI, 7.25–19.08]) and persisted after a booster dose (2.64 [95% CI, 1.25–5.58]). Associations were stronger in men younger than 40 years for all vaccines. In men younger than 40 years old, the number of excess myocarditis events per million people was higher after a second dose of mRNA-1273 than after a positive SARS-CoV-2 test (97 [95% CI, 91–99] versus 16 [95% CI, 12–18]). In women younger than 40 years, the number of excess events per million was similar after a second dose of mRNA-1273 and a positive test (7 [95% CI, 1–9] versus 8 [95% CI, 6–8]). Conclusions: Overall, the risk of myocarditis is greater after SARS-CoV-2 infection than after COVID-19 vaccination and remains modest after sequential doses including a booster dose of BNT162b2 mRNA vaccine. However, the risk of myocarditis after vaccination is higher in younger men, particularly after a second dose of the mRNA-1273 vaccine.

ObjectivesTo characterise the quality of life, healthcare use and costs associated with early antibiotic treatment of influenza-like illness (ILI) in ‘at-risk’ children.DesignEconomic analysis of a two-arm double-blind parallel group pragmatic randomised controlled trial.SettingChildren were recruited from community-based healthcare settings, including general practices, walk-in centres and hospital ambulatory care.ParticipantsChildren with risk factors for influenza-related complications, including respiratory, cardiac and neurological conditions, who presented within the first 5 days of an ILI.InterventionsCo-amoxiclav 400/57 suspension or placebo.Outcome measuresThis economic analysis focused on quality of life measured by the EQ-5D-Y, symptoms assessed by the Canadian Acute Respiratory Infection and Flu Scale (CARIFS), healthcare use and costs including medication, hospital visits and admissions, general practitioner and nurse contacts. Outcomes were assessed for up to 28 days post randomisation.ResultsInformation on resource use, EQ-5D-Y (day 28) and CARIFS (day 7) was available for 265 (98%), 72 (27%) and 123 (45%) out of 271 participants, respectively. Average costs in the co-amoxiclav group were £25 lower (95% CI −£113 to £65), but this difference was not statistically significant (p=0.566). The difference in EQ-5D-Y scores between groups was also not statistically significant (−0.014 (95% CI −0.124 to 0.096), p=0.798). However, day 7 CARIFS scores were 3.5 points lower in the co-amoxiclav arm (95% CI −6.9 to −0.1, p=0.044).ConclusionsOur findings did not show evidence that early co-amoxiclav treatment improves quality of life or reduces healthcare use and costs in ‘at-risk’ children with ILI, but may reduce symptom severity though confirmation from further research would be important. Reliable data collection from children’s parents/carers was challenging, and resulted in high levels of missing data, which is common in pragmatic trials involving children with acute respiratory tract infections.Trial registration numberISRCTN70714783; EudraCT 2013-002822-21.

The United Kingdom has been profoundly affected by the coronavirus disease 2019 (COVID19) pandemic. In our population of over 66 million, to date we have had over 4.3 million confirmed infections with over 127 000 deaths (10 April 2021).1 Vaccination has provided an opportunity to limit the impact of COVID19 on our population and hopefully reduce the risk of significant mortality in any third wave.

ABSTRACTIn an updated self-controlled case series analysis of 42,200,614 people aged 13 years or more, we evaluate the association between COVID-19 vaccination and myocarditis, stratified by age and sex, including 10,978,507 people receiving a third vaccine dose. Myocarditis risk was increased during 1-28 days following a third dose of BNT162b2 (IRR 2.02, 95%CI 1.40, 2.91). Associations were strongest in males younger than 40 years for all vaccine types with an additional 3 (95%CI 1, 5) and 12 (95% CI 1,17) events per million estimated in the 1-28 days following a first dose of BNT162b2 and mRNA-1273, respectively; 14 (95%CI 8, 17), 12 (95%CI 1, 7) and 101 (95%CI 95, 104) additional events following a second dose of ChAdOx1, BNT162b2 and mRNA-1273, respectively; and 13 (95%CI 7, 15) additional events following a third dose of BNT162b2, compared with 7 (95%CI 2, 11) additional events following COVID-19 infection. An association between COVID-19 infection and myocarditis was observed in all ages for both sexes but was substantially higher in those older than 40 years. These findings have important implications for public health and vaccination policy.FundingHealth Data Research UK.

Introduction: We describe post-COVID symptomatology in a national sample of 11-17-year-old children and young people (CYP) with PCR-confirmed SARS-CoV-2 infection compared to test-negative controls. Methods and analysis: A cohort study of test-positive (n=3,065) and age-, sex- and geographically-matched test-negative CYP (n=3,739) completed detailed questionnaires 3 months post-test. Results : At PCR-testing, 35.4% of test-positives and 8.3% of test-negatives had any symptoms whilst 30.6% and 6.2%, respectively, had 3+ symptoms. At 3 months post-testing, 66.5% of test-positives and 53.3% of test-negatives had any symptoms, whilst 30.3% and 16.2%, respectively, had 3+ symptoms. Latent class analysis identified two classes, characterised by “few” or “multiple” symptoms. This latter class was more frequent among test-positives, females, older CYP and those with worse pre-test physical and mental health. Discussion: Test-positive CYP had a similar symptom profile to test-negative CYP but with higher prevalence of single and, particularly, multiple symptoms at PCR-testing and 3 months later.

Importance Although children mainly experience mild COVID-19 disease, hospitalization rates are increasing, with limited understanding of underlying factors. There is an established association between race and severe COVID-19 outcomes in adults in England; however, whether a similar association exists in children is unclear. Objective To investigate the association between race and childhood COVID-19 testing and hospital outcomes. Design, Setting, Participants In this cohort study, children (0-18 years of age) from participating family practices in England were identified in the QResearch database between January 24 and November 30, 2020. The QResearch database has individually linked patients with national SARS-CoV-2 testing, hospital admission, and mortality data. Exposures The main characteristic of interest is self-reported race. Other exposures were age, sex, deprivation level, geographic region, household size, and comorbidities (asthma; diabetes; and cardiac, neurologic, and hematologic conditions). Main Outcomes and Measures The primary outcome was hospital admission with confirmed COVID-19. Secondary outcomes were SARS-CoV-2-positive test result and any hospital attendance with confirmed COVID-19 and intensive care admission. Results Of 2 576 353 children (mean [SD] age, 9.23 [5.24] years; 48.8% female), 410 726 (15.9%) were tested for SARS-CoV-2 and 26 322 (6.4%) tested positive. A total of 1853 children (0.07%) with confirmed COVID-19 attended hospital, 343 (0.01%) were admitted to the hospital, and 73 (0.002%) required intensive care. Testing varied across race. White children had the highest proportion of SARS-CoV-2 tests (223 701/1 311 041 [17.1%]), whereas Asian children (33 213/243 545 [13.6%]), Black children (7727/93 620 [8.3%]), and children of mixed or other races (18 971/147 529 [12.9%]) had lower proportions. Compared with White children, Asian children were more likely to have COVID-19 hospital admissions (adjusted odds ratio [OR], 1.62; 95% CI, 1.12-2.36), whereas Black children (adjusted OR, 1.44; 95% CI, 0.90-2.31) and children of mixed or other races (adjusted OR, 1.40; 95% CI, 0.93-2.10) had comparable hospital admissions. Asian children were more likely to be admitted to intensive care (adjusted OR, 2.11; 95% CI, 1.07-4.14), and Black children (adjusted OR, 2.31; 95% CI, 1.08-4.94) and children of mixed or other races (adjusted OR, 2.14; 95% CI, 1.25-3.65) had longer hospital admissions (≥36 hours). Conclusions and Relevance In this large population-based study exploring the association between race and childhood COVID-19 testing and hospital outcomes, several race-specific disparities were observed in severe COVID-19 outcomes. However, ascertainment bias and residual confounding in this cohort study should be considered before drawing any further conclusions. Overall, findings of this study have important public health implications internationally.