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Objective: To assess the incidence of maternal group B Streptococcus (GBS) infection in England. Design: Population surveillance augmented through data linkage. Setting: England. Population: All pregnant women accessing the National Health Service (NHS) in England. Methods: Invasive GBS (iGBS) infections during pregnancy or within 6 weeks of childbirth were identified by linking Public Health England (PHE) national microbiology surveillance data for 2014 to NHS hospital admission records. Capsular serotypes of GBS were determined by reference laboratory typing of clinical isolates from women aged 15–44 years. Post‐caesarean section surgical site infection (SSI) caused by GBS was identified in 21 hospitals participating in PHE SSI surveillance (2009–2015). Main outcome measures: iGBS rate per 1000 maternities; risk of GBS SSI per 1000 caesarean sections. Results: Of 1601 patients diagnosed with iGBS infections in England in 2014, 185 (12%) were identified as maternal infections, a rate of 0.29 (95% CI 0.25–0.33) per 1000 maternities and representing 83% of all iGBS cases in women aged 18–44 years. Seven (3.8%) were associated with miscarriage. Fetal outcome identified excess rates of stillbirth (3.4 versus 0.5%) and extreme prematurity (<28 weeks of gestation, 3.7 versus 0.5%) compared with national averages (P < 0.001). Caesarean section surveillance in 27 860 women (21 hospitals) identified 47 cases of GBS SSI, with an estimated 4.24 (3.51–5.07) per 1000 caesarean sections, a median time‐to‐onset of 10 days (IQR 7–13 days) and ten infections that required readmission. Capsular serotype analysis identified a diverse array of strains with serotype III as the most common (43%). Conclusions: Our assessment of maternal GBS infection in England indicates the potential additional benefit of GBS vaccination in preventing adverse maternal and fetal outcomes. [ABSTRACT FROM AUTHOR]

The meningococcal group B vaccine, 4CMenB, is a broad-spectrum, recombinant protein vaccine that is licensed for protection against meningococcal group B disease in children and adults. Over the past decade, several observational studies supported by laboratory studies have reported protection by 4CMenB against gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae. Gonorrhoea is a major global public health problem, with rising numbers of diagnoses and increasing resistance to multiple antibiotics. In England, more than 82 000 cases of gonorrhoea were diagnosed in 2022, with nearly half of the cases diagnosed among gay, bisexual, and other men who have sex with men. There are currently no licensed vaccines against gonorrhoea but 4CMenB is estimated to provide 33-47% protection against gonorrhoea. On Nov 10, 2023, the UK Joint Scientific Committee on Vaccination and Immunisation agreed that a targeted programme should be initiated using 4CMenB to prevent gonorrhoea among individuals at higher risk of infection attending sexual health services in the UK. This decision was made after reviewing evidence from retrospective and prospective observational studies, laboratory and clinical data, national surveillance reports, and health economic analyses. In this Review, we summarise the epidemiology of invasive meningococcal disease and gonorrhoea in England, the evidence supporting the use of 4CMenB for protection against gonorrhoea, and the data needed to inform long-term programme planning and extension to the wider population., Competing Interests: Declaration of interests PJW has received payment from Pfizer for teaching of mathematical modelling of infectious disease transmission and vaccination. RB performs contract serology on behalf of UKHSA for GlaxoSmithKline, Pfizer, and Sanofi but receives no personal remuneration. SNL performs contract research for St George's University of London for vaccine manufacturers but receives no personal remuneration. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. All rights reserved.)

Recent months have seen an increase in pertussis cases in several countries across the Northern and Southern hemispheres. The lack of immune stimulation during the COVID-19 pandemic due to the reduced circulation of Bordetella pertussis, the pathogen responsible for pertussis, is likely to have led to increased population susceptibility which has been magnified the typical three to five yearly cyclical peaks in activity. Maternal immunization for pertussis proves highly effective in protecting infants under three months of age. It's also critical for immunizers and parents to maintain high and timely immunization uptake to ensure infants receive maximum early protection when they are most at risk of severe disease., Competing Interests: Declarations of competing interest AK is the Vice President for academia and strategy of the RCOG. All authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Paediatric pneumococcal conjugate vaccine (PCV) programmes in England using seven-valent PCV (PCV7) in 2006 and 13-valent PCV (PCV13) in 2010 have reduced vaccine-type invasive pneumococcal disease, but the overall effect has been reduced by an increase in invasive pneumococcal disease due to non-vaccine serotypes and serotype 3. We developed pneumococcal transmission models to investigate the potential effect on invasive pneumococcal disease of higher valency PCVs covering an additional two (ie, 15-valent PCV [PCV15]) or seven serotypes (ie, 20-valent PCV [PCV20]) in England., Methods: We conducted a modelling study using realistic, age-structured, and compartmental deterministic models fitted to carriage data from before the introduction of PCVs and invasive pneumococcal disease data from before and after the introduction of PCV7 and PCV13 in England from the UK Heath Security Agency invasive pneumococcal disease surveillance system. We estimated key parameters, including PCV7 and PCV13 efficacy against vaccine-type carriage and invasiveness of PCV7 serotypes; the additional serotypes in PCV13, PCV15 and PCV20; and non-vaccine serotypes. We simulated the effect of transitioning from PCV13 to PCV15 or PCV20 in infants under the current 1 + 1 vaccination schedule and investigated the effect of reduced carriage protection against PCV13 serotypes due to attenuation of immunogenicity in higher valency vaccines., Findings: Our results suggest that PCV15 might increase overall invasive pneumococcal disease as the reduction in vaccine-type invasive pneumococcal disease would be counterbalanced by an increase in non-PCV15 invasive pneumococcal disease. By contrast, PCV20 is projected to have a substantial impact on overall invasive pneumococcal disease due to higher invasiveness of the additional serotypes covered by PCV20 than the replacing non-vaccine serotypes. Reduced carriage protection against PCV13 serotypes with higher valency vaccines would amplify these effects., Interpretation: Replacing PCV13 with PCV20 is likely to have a substantial public health benefit, but PCV15 could potentially increase the overall burden of disease., Funding: UK Health Security Agency and National Institute of Health Research., Competing Interests: Declaration of interests The Immunisation and Vaccine Preventable Diseases Division of the UK Health Security Agency provides vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infections, which the companies are required to submit to the Medicines and Healthcare Products Regulatory Agency in compliance with the companies' risk management strategy. A cost recovery charge is made for these reports. SNL performs contract research on behalf of St George's University of London and the UK Health Security Agency for pharmaceutical companies but receives no personal remuneration. The Respiratory and Vaccine Preventable Bacteria Reference Unit of the UK Health Security Agency has received grant funding from vaccine manufacturers for investigator-led research projects on pneumococcal surveillance. EM receives support from the National Institute for Health Research (NIHR) Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England (Grant Reference NIHR200929). All other authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Haemophilus influenzae serotype b (Hib) conjugate vaccines have been highly successful in reducing the Hib disease worldwide. Recently, several European countries have reported an increase in invasive Hib disease. We aimed to describe the epidemiology, clinical characteristics, genomic trends, and outcomes of invasive Hib disease over the past 11 years in England., Methods: The UK Health Security Agency (UKHSA) conducts national surveillance of invasive H influenzae disease and hosts a national reference laboratory for confirmation and serotyping. General practitioners are contacted to complete a surveillance questionnaire for confirmed Hib cases. Invasive Hib isolates routinely undergo whole genome sequencing., Results: During 2012/13-2022/23, there were 6881 invasive H. influenzae infections, of which 5852 (85%) were serotyped; most isolates (4881, 83%) were non-typeable H. influenzae, followed by Hif (591, 10%), Hie (189, 3%), Hib (118, 2%) and Hia (54, 1.0%). The median age for invasive Hib disease was 51 years, and most cases (84%, 99/118) were in adults. Children accounted for 19 cases (16%), including 13 (11%) in <1 year-olds and 6 (5%) in 1-5-year-olds. Bacteraemic pneumonia was the most common diagnosis (66/118, 56%). Hib case-fatality rate was 5.9% (7/118), with the last fatality reported in 2016. Among 64 sequenced strains during 2016/17-2022/2023, most (56/64, 88%) belonged to the CC6 lineage (representing ST6 and single locus variants of ST6)., Conclusions: In England, invasive Hib disease remains rare with no evidence of any increase in incidence and is rarely fatal, affecting mainly adults with underlying conditions, who typically develop pneumonia., Competing Interests: Declaration of Competing Interest None., (Copyright © 2024. Published by Elsevier Ltd.)

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., (© 2024. The Author(s).)

Objective: To compare immunological responses of preterm infants to a four-component meningococcal B vaccine (4CMenB; Bexsero) following a 2+1 vs a 3+1 schedule, and to describe reactogenicity of routine vaccines., Design: An open-label, phase IV randomised study conducted across six UK sites., Setting: Neonatal units, postnatal wards, community recruitment following discharge., Participants: 129 preterm infants born at a gestation of <35 weeks (64 in group 1 (2+1), 65 in group 2 (3+1)) were included in the analysis. Analysis was completed for postprimary samples from 125 participants (59 in group 1, 66 in group 2) and for postbooster samples from 118 participants (59 in both groups)., Interventions: Infants randomised to 4CMenB according to a 2+1 or a 3+1 schedule, alongside routine vaccines., Main Outcome Measures: Serum bactericidal antibody (SBA) assays performed at 5, 12 and 13 months of age: geometric mean titres (GMTs) and proportions of infants achieving titres ≥4 compared between groups., Results: There were no significant differences in SBA GMTs between infants receiving a 2+1 compared with a 3+1 schedule following primary or booster vaccination, but a significantly higher proportion of infants had an SBA titre ≥4 against strain NZ98/254 (porin A) at 1 month after primary vaccination using a 3+1 compared with a 2+1 schedule (3+1: 87% (95% CI 76 to 94%), 2+1: 70% (95% CI 56 to 81%), p=0.03).At 12 weeks of age those in the 3+1 group, who received a dose of 4CMenB, had significantly more episodes of fever >38.0°C than those in the 2+1 group who did not (group 2+1: 2% (n=1); 3+1: 14% (n=9); p=0.02)., Conclusions: Both schedules were immunogenic in preterm infants, although a lower response against strain NZ98/254 was seen in the 2+1 schedule; ongoing disease surveillance is important in understanding the clinical significance of this difference., Trial Registration Number: NCT03125616., Competing Interests: Competing interests: JL and RB perform contract research on behalf of UKHSA for GlaxoSmithKline (GSK), Pfizer and Sanofi. JC works for an institution which conducts meningococcal vaccine research on behalf of GSK; he receives no personal payment or inducement of any kind. MS was an employee of the University of Oxford and Oxford University Hospitals Foundation NHS trust up until September 2022, and in this role acted as an investigator for clinical research studies funded or otherwise supported by the vaccine manufacturers GSK, Janssen, AstraZeneca, Pfizer, Novavax and MCM vaccines. He received no personal financial benefit for this work. As of September 2022, MS has been an employee of Moderna UK and holds equity in this company; however, all study activities and data analysis were completed before this date., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Young people living with Long COVID are learning to navigate life with a constellation of poorly understood symptoms. Most qualitative studies on experiences living with Long COVID focus on adult populations. This study aimed to understand the experiences of young people living with Long COVID. Qualitative, semi-structured interviews were conducted ( n = 16); 11 young people (aged 13-19) and five parents were recruited from the Children and Young People with Long COVID (CLoCk) study ( n = 11) or its patient and public involvement and engagement (PPIE) group ( n = 5). Thematic analysis generated four themes: (i) Unravelling Long COVID: Exploring Symptom Journeys and Diagnostic Dilemmas; (ii) Identity Disruption and Adjustment; (iii) Long COVID's Ripple Effect: the impact on Mental Health, Connections, and Education; and (iv) Navigating Long COVID: barriers to support and accessing services. Treatment options were perceived as not widely available or ineffective, emphasising the need for viable and accessible interventions for young people living with Long COVID., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Terence Stephenson is Chair of the Health Research Authority and therefore recused himself from the Research Ethics Application. Trudie Chalder acknowledges the financial support of the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to the South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry at King’s College London. Tamsin Ford’s research group receives funding from Place2Be for research methods consultancy. All remaining authors have no conflicts of interest.

Invasive meningococcal disease (IMD), caused by infection with the bacterium Neisseria meningitidis, usually manifests as meningitis or septicemia and can be severe and life-threatening (1). Six serogroups (A, B, C, W, X, and Y) account for most cases (2). N. meningitidis is transmitted person-to-person via respiratory droplets and oropharyngeal secretions. Asymptomatic persons can carry N. meningitidis and transmit the bacteria to others, potentially causing illness among susceptible persons. Outbreaks can occur in conjunction with large gatherings (3,4). Vaccines are available to prevent meningococcal disease. Antibiotic prophylaxis for close contacts of infected persons is critical to preventing secondary cases (2)., Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. Jay Lucidarme, Stephen A. Clark, and Ray Borrow report performing contract research on behalf of the UK Health Security Agency (UKHSA) for GSK, Pfizer, and Sanofi. Muhamed-Kheir Taha reports performing contract research on behalf of the Institut Pasteur for GSK, Pfizer, and Sanofi. Shamez N. Ladhani reports performing contract research on behalf of the UKHSA and St. George’s University of London for GSK, Pfizer, Merck Sharp & Dohme, and Sanofi. Helen Campbell and Mary Ramsay report receipt of a recovery charge by the Immunisation and Vaccine Preventable Diseases Division at UKHSA for provision to vaccine manufacturers (GSK, Pfizer, and Sanofi) of postmarketing surveillance reports on meningococcal, Haemophilus influenzae, and pneumococcal infections, which are required by the U.K. Licensing Authority in compliance with their risk management strategy. Jennifer Zipprich reports that her spouse is employed by Pfizer. No other potential conflicts of interest were disclosed.

Children have been disproportionately affected by the COVID-19 pandemic. Despite evidence of a very low risk of severe disease, children were subjected to extensive lockdown, restriction and mitigation measures, including school closures, to control the rapid spread of SARS-CoV-2 in most parts of the world. In this review we summarise the UK experience of COVID-19 in children four years into the largest and longest pandemic of this century. We address the risks of SARS-CoV-2 infection, immunity, transmission, severity and outcomes in children. We also assess the implementation, uptake, effectiveness and impact of COVID-19 vaccination, as well as the emergence, evolution and near disappearance of PIMS-TS (paediatric inflammatory multisystem syndrome temporally associated with SARS-CoV-2) and current understanding of long COVID in children. This review consolidates current knowledge on childhood COVID-19 and emphasises the importance of continued research and the need for research-driven public health actions and policy decisions, especially in the context of new variants and future vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Guidelines for the prevention and treatment of infection in patients with an absent or dysfunctional spleen were published by the British Committee for Standards in Haematology in 1996 and updated in 2002 and 2011. With advances in vaccinations and changes in patterns of infection, the guidelines required updating. Key aspects included in this guideline are the identification of patients at risk of infection, patient education and information and immunisation schedules. This guideline does not address the non-infective complications of splenectomy or functional hyposplenism (FH). This replaces previous guidelines and significantly revises the recommendations related to immunisation. Patients at risk include those who have undergone surgical removal of the spleen, including partial splenectomy and splenic embolisation, and those with medical conditions that predispose to FH. Immunisations should include those against Streptococcus pneumoniae (pneumococcus), Neisseria meningitidis (meningococcus) and influenza. Haemophilus influenzae type b (Hib) is part of the infant immunisation schedule and is no longer required for older hyposplenic patients. Treatment of suspected or proven infections should be based on local protocols and consider relevant anti-microbial resistance patterns. The education of patients and their medical practitioners is essential, particularly in relation to the risk of serious infection and its prevention. Further research is required to establish the effectiveness of vaccinations in hyposplenic patients; infective episodes should be regularly audited. There is no single group ideally placed to conduct audits into complications arising from hyposplenism, highlighting a need for a national registry, as has proved very successful in Australia or alternatively, the establishment of appropriate multidisciplinary networks., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Background: The UK transition from a 2 + 1 to a 1 + 1 infant immunisation schedule with the 13-valent pneumococcal conjugate vaccine (PCV13) on Jan 1, 2020, coincided with the start of the COVID-19 pandemic. We describe the epidemiology of invasive pneumococcal disease (IPD) in England over 6 financial years (April 1 to March 31) between 2017-18 and 2022-23., Methods: We used prospective national surveillance data, including serotyping and whole-genome sequencing of invasive isolates, to analyse IPD trends in England by age and financial year. We compared breakthrough infections and vaccine failure rates in 2022-23 among children eligible for the 1 + 1 schedule with rates in cohorts of children eligible for the 2 + 1 schedule between 2017-18 and 2019-20. We assessed genomic changes over time by comparing Global Pneumococcal Sequencing Clusters and multilocus sequence types among PCV13 serotypes causing IPD., Findings: There were 4598 laboratory-confirmed IPD cases in 2022-23, 3025 in 2021-22, 1240 in 2020-21, and 5316 in 2019-20. IPD incidence in 2022-23 was 14% lower than in 2019-20 (incidence rate ratio [IRR] 0·86, 95% CI 0·81-0·91; p<0·001). IPD incidence in 2022-23 compared with 2019-20 was 34% higher in children (aged <15 years) (378 cases vs 292 cases; IRR 1·34, 95% CI 1·08-1·68; p=0·009) and 17% lower in adults (aged 15 years and older; 4220 vs 5024; 0·83, 0·78-0·88; p<0·001). The proportion of PCV13-type IPD increased from 19·4% (95% CI 18·2-20·4; 957 of 4947) in 2019-20 to 29·7% (28·3-31·0; 1283 of 4326) in 2022-23, mainly due to serotype 3, but also serotypes 19F, 19A, and 4, alongside a decrease in non-PCV13 serotypes 8, 12F, and 9N. The increase in IPD incidence due to serotypes 3, 19A, and 19F was driven by clonal expansion of previously circulating strains, whereas serotype 4 expansion was driven by newer strains (ie, sequence types 801 and 15603). Breakthrough infections and vaccine failure rates were similar in children eligible for the 1 + 1 (1·08 per 100 000 person-years) and 2 + 1 (0·76 per 100 000 person-years; IRR 1·42, 95% CI 0·78-2·49; p=0·20) PCV13 schedules., Interpretation: Overall, IPD incidence in England was lower in 2022-23, 2 years after removal of pandemic restrictions, than in 2019-20. Breakthrough and vaccine failure rates were not significantly different between children who received the 1 + 1 compared with the 2 + 1 PCV13 immunisation schedule. The post-pandemic increase in childhood IPD incidence and especially PCV13-type IPD will require close monitoring., Funding: None., Competing Interests: Declaration of interests The Immunisation and Vaccine Preventable Diseases Division (UKHSA) provides vaccine manufacturers with post-marketing surveillance reports on pneumococcal and meningococcal infections, which the companies are required to submit to the Medicines and Healthcare products Regulatory Agency in compliance with the companies' Risk Management Strategy. A cost recovery charge is made for these reports. SNL performs contract research on behalf of St George's University of London and the UKHSA for pharmaceutical companies but receives no personal remuneration. The Respiratory and Vaccine Preventable Bacteria Reference Unit (UKHSA) has received grant funding from vaccine manufacturers for investigator-led research projects on pneumococcal surveillance. All other authors declare no competing interests., (Crown Copyright © 2024 Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.)

Our previous study in children and young people (CYP) at 3- and 6-months post-infection showed that 12-16% of those infected with the Omicron (B.1.1.529) variant of SARS-CoV-2 met the research definition of Long Covid, with no differences between first-positive and reinfected CYP. The primary objective of the current study is to explore the impact of the Omicron variant of SARS-CoV-2 infection on young people 12 months post infection. 345 CYP aged 11-17 years with a first laboratory-confirmed infection with the Omicron variant and 360 CYP reinfected with the Omicron variant completed an online questionnaire assessing demographics, symptoms, and their impact shortly after testing and again at 3-, 6-and 12-months post-testing. Vaccination status was determined from information held at UKHSA. Comparisons between groups were made using chi-squared, Mann-Whitney U, and Kruskal-Wallis tests. The most common symptoms in first-positive and reinfected CYP 12-months post-testing were tiredness (35.7 and 33.6% respectively) and sleeping difficulties (27.5 and 28.3% respectively). Symptom profiles, severity and impact were similar in the two infection status groups. Overall, by 12-months, 17.4% of first-positives and 21.9% of reinfected CYP fulfilled the research consensus Long Covid definition (p = 0.13). 12-months post Omicron infection, there is little difference between first-positive and reinfected CYP with respect to symptom profiles and impact. Clinicians may not therefore need to consider number of infections and type of variant when developing treatment plans. Further studies are needed to assess causality of reported symptoms up to 12-months after SARS-CoV-2 infection., (© 2024. The Author(s).)

Objective: Neonatal infection with wildtype SARS-CoV-2 is rare and good outcomes predominate. We investigated neonatal outcomes using national population-level data to describe the impact of different SARS-CoV-2 variants., Design: Prospective population-based cohort study., Setting: Neonatal, paediatric and paediatric intensive care inpatient care settings in the UK., Patients: Neonates (first 28 days after birth) with confirmed SARS-CoV-2 infection who received inpatient care, March 2020 to April 2022. Neonates were identified through active national surveillance with linkage to national SARS-CoV-2 testing data, routinely recorded neonatal data, paediatric intensive care data and obstetric and perinatal mortality surveillance data., Outcomes: Presenting signs, clinical course, severe disease requiring respiratory support are presented by the dominant SARS-CoV-2 variant in circulation at the time., Results: 344 neonates with SARS-CoV-2 infection received inpatient care; breakdown by dominant variant: 146 wildtype, 123 alpha, 57 delta and 18 omicron. Overall, 44.7% (153/342) neonates required respiratory support; short-term outcomes were good with 93.6% (322/344) of neonates discharged home. Eleven neonates died: seven unrelated to SARS-CoV-2 infection, four were attributed to neonatal SARS-CoV-2 infection (case fatality 4/344, 1.2% 95% CI 0.3% to 3.0%) of which three were born preterm due to maternal COVID-19. More neonates were born very preterm (23/54) and required invasive ventilation (27/57) when delta variant was predominant, and all four SARS-CoV-2-related deaths occurred in this period., Conclusions: Inpatient care for neonates with SARS-CoV-2 was uncommon. Although rare, severe neonatal illness was more common during the delta variant period, potentially reflecting more severe maternal disease and associated preterm birth., Trial Registration Number: ISRCTN60033461., Competing Interests: Competing interests: MK, MAQ, CG and JJK received grants from the UK NIHR Policy Research Programme in relation to the submitted work. KEF, AM, MH, AP, SNL, ESD, DS, CD and HM declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

A number of countries including the UK are currently experiencing large outbreaks of measles affecting mainly young children but also adolescents and young adults. Women of childbearing age are a particular group of concern because the 1988 Wakefield Lancet paper, which falsely asserted a connection between the MMR vaccine and autism, was associated with a large and sharp decline in childhood MMR uptake over several years. This has left large cohorts of non-immune adolescents and young adults (born between 1998 and 2004), including young women who are now of childbearing age and remain susceptible to measles as well as rubella. Pregnant mothers are at higher risk of serious complications, such as pneumonia, with adverse pregnancy complications including fetal loss, premature birth, and neonatal death. Measles infection may also result in subacute sclerosing panencephalitis (SSPE), a very rare but very severe and invariably fatal neurodegenerative complication that typically manifests many years after acute measles infection but can have a short-onset latency with a fulminant course in pregnant women. Here, we summarise the epidemiology of measles infection, factors associated with the current measles outbreaks, as well as the risks and outcomes of measles, including SSPE, in pregnancy. We propose an algorithm for clinical management of measles infection in pregnancy. We also highlight the importance of early liaison with local health protection teams for risk assessment, diagnosis and management of suspected measles in pregnancy and close contacts as well as susceptible pregnant women exposed to a person with measles in the community., Competing Interests: AK is Vice President of the RCOG. We declare no competing interests. All other authors declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Background: People living with HIV have an increased risk of meningococcal disease. The Propositive trial evaluated co-administration of two doses of a four-component recombinant protein-based MenB vaccine (4CMenB) and a quadrivalent conjugate polysaccharide MenACWY vaccine (MenACWY-CRM197) given 1 month apart in people with HIV. The follow-up trial assessed the immunogenicity of these vaccines at 1.5 and 2.5 years after primary vaccination., Methods: Participants who completed the parent Propositive trial were invited to the follow-up study. Immunogenicity analysis was performed at 18 and 30 months after primary vaccination. Primary outcome measures were serum bactericidal antibody (SBA) geometric mean titres (GMTs) against three MenB reference strains and the proportion of participants maintaining a protective SBA titre of ≥4 at 18 and 30 months. Secondary outcome measures were SBA GMTs against MenA, C, W, and Y serogroups and the proportion of participants maintaining a protective SBA titre of ≥8 at 18 and 30 months. The trial is registered with Clinicaltrials.gov (NCT042394300)., Results: A total of 40 participants aged 22-47 years were enrolled. Geometric mean titres waned by 18 and 30 months but remained higher than pre-vaccination for all MenB strains and MenA, C, W, and Y. In total, 75%-85% of participants retained protective SBA titres by 30 months against individual MenB strains, whereas 68.8% of patients retained protective antibody titres against all three MenB strains. Antibodies against MenC waned more rapidly than did those against MenA, W, and Y. The proportion of participants with protective titres against MenC at 30 months was also lower (46.9%) than that with protective titres against MenA (87.5%), W (78.1%), and Y (87.5%)., Conclusions: Immune responses against MenB in our cohort of people living with HIV at 2.5 years of follow-up were reassuring, with 68.8% of participants retaining protection against all three reference strains. However, responses against MenC were lower than those against MenA, W, and Y serogroups., (© 2023 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Background: Mask mandates for children during the COVID-19 pandemic varied in different locations. A risk-benefit analysis of this intervention has not yet been performed. In this study, we performed a systematic review to assess research on the effectiveness of mask wearing in children., Methods: We performed database searches up to February 2023. The studies were screened by title and abstract, and included studies were further screened as full-text references. A risk-of-bias analysis was performed by two independent reviewers and adjudicated by a third reviewer., Results: We screened 597 studies and included 22 in the final analysis. There were no randomised controlled trials in children assessing the benefits of mask wearing to reduce SARS-CoV-2 infection or transmission. The six observational studies reporting an association between child masking and lower infection rate or antibody seropositivity had critical (n=5) or serious (n=1) risk of bias; all six were potentially confounded by important differences between masked and unmasked groups and two were shown to have non-significant results when reanalysed. Sixteen other observational studies found no association between mask wearing and infection or transmission., Conclusions: Real-world effectiveness of child mask mandates against SARS-CoV-2 transmission or infection has not been demonstrated with high-quality evidence. The current body of scientific data does not support masking children for protection against COVID-19., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Research on the long-term impact on COVID-19 in children and young people (CYP) has been published at pace. We aimed to update and refine an earlier systematic review and meta-analysis to assess the current evidence for Post-COVID-19 Condition in CYP., Methods: Studies from the previous systematic review were combined with studies from a systematic search from July 2021 to November 2022 (registration PROSPERO CRD42021233153). Eligible studies included CYP aged ≤19 years with confirmed or probable SARS-CoV-2 infection and symptoms persisting at least 12 weeks., Findings: 55 studies (n = 1,139,299 participants) were included. Over two-hundred symptoms were associated with Post COVID-19 Condition. Gastrointestinal problems, headaches, cough and fever were among the most prevalent symptoms with rates of 50.2%, 35.6%, 34.7% and 25.8% respectively. Twenty-one symptoms from 11 studies were suitable for meta-analysis. There were significantly higher pooled estimates of proportions of symptoms for altered / loss of smell or taste, dyspnoea, fatigue, and myalgia in CYP with confirmed SARS-CoV-2 infection. Heterogeneity was high suggesting substantial variation amongst the included studies., Conclusions: Many CYP continue to experience symptoms after SARS-CoV-2 infection. Efforts to aid early identification and intervention of those most in need is warranted and the consequences of COVID-19 for CYP call for long-term follow-up., Competing Interests: The authors have read the journal’s policy and have the following competing interests: Terence Stephenson is the current Chair of the Health Research Authority (HRA) for England. The Health Research Authority reimburses his university, the University College London, for his time. He has recused himself from research studies in which he is personally involved and which require ethical approval from the HRA. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Behnood et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: During the COVID-19 pandemic children and young people (CYP) were socially restricted during a stage of life crucial to development, potentially putting an already vulnerable population at higher risk of loneliness, social isolation, and poorer wellbeing. The objectives of this study are to conduct an exploratory analysis into loneliness before and during the pandemic, and determine which self-reported factors are associated with loneliness., Methods and Findings: Participants from The Children with Long COVID (CLoCk) national study were invited to take part via an online survey, with a total of 31,017 participants taking part, 31,016 of which reported on their experience of loneliness. Participants retrospectively answered questions on demographics, lifestyle, physical health and mental health and loneliness before the pandemic and at the time of answering the survey. Before the pandemic 6.5% (2,006/31,016) of participants reported experiencing loneliness "Often/Always" and at the time of survey completion 17.4% (5,395/31,016) reported feeling lonelier. There was an association between meeting the research definition of long COVID and loneliness [3.49 OR, 95%CI 3.28-3.72]. CYP who reported feeling lonelier at the time of the survey than before the pandemic were assigned female at birth, older CYP, those from Black/African/Caribbean/Black British or other ethnicity groups, those that had 3-4 siblings and lived in more deprived areas., Conclusions: We demonstrate associations between multiple factors and experiences of loneliness during the pandemic. There is a need for a multi-faceted integrated approach when developing interventions targeted at loneliness. It is important to follow up the CYP involved at regular intervals to investigate the progression of their experience of loneliness over time., Competing Interests: TS is Chair of the Health Research Authority and therefore recused himself from the Research Ethics Application. TC is a member of the National Institute for Health and Care Excellence committee for long COVID. She has written self-help books on chronic fatigue and has done workshops on chronic fatigue and post infectious syndromes. TC also has a grant looking at long COVID in adults. MGS reports grants from MRC and Health Protection Research Unit in Emerging & Zoonotic Infections, University of Liverpool. He also reports a role as Independent external and non-remunerated member of Pfizer’s External Data Monitoring Committee for their mRNA vaccine program. He is Chair of Infectious Disease Scientific Advisory Board for Integrum Scientific LLC, Greensboro, NC, USA and director of MedEx Solutions Ltd. He reports minority stock ownership for Integrum Scientific LLC, Greensboro, NC, USA and majority stock ownership for MedEx Solutions Ltd. He also reports a gift from Chiesi Farmaceutici SPA to his institution of a clinical trial investigational medicinal product without encumbrance and distribution of same to trial sites. He is also a non-remunerated independent member of HMG UK Scientific Advisory Group for Emergencies (SAGE, COVID-19 Response) and HMG UK New Emerging Respiratory Virus Threats Advisory Group (NERVTAG). All remaining authors have no conflicts of interest. Data cannot be shared publicly due to ethical and legal considerations. All requests for data will be reviewed by the Children & young people with Long Covid (CLoCk) study team, to verify whether the request is subject to any intellectual property or confidentiality obligations. Requests for access to the participant-level data from this study can be submitted via email to Clock@ukhsa.gov.uk with detailed proposals for approval. A signed data access agreement with the CLoCk team is required before accessing shared data. This does not alter our adherence to PLOS ONE policies on sharing data and materials.", (Copyright: © 2023 McOwat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: In 2020, COVID-19 pandemic restrictions led to a major suppression of meningococcal disease in England. Here we describe the epidemiology of invasive meningococcal disease in the three years prior to the COVID-19 pandemic, and the three years immediately after the introduction of restrictions., Methods: The UK Health Security Agency conducts national meningococcal disease surveillance in England consisting of laboratory-based case confirmation with strain characterisation by culture and/or molecular detection, as well as clinical follow-up of all cases., Results: In the pre-pandemic period, 554-742 IMD cases were laboratory-confirmed per year. MenB caused 57.2% of cases, followed by MenW (22.7%), MenY (10.6%) and MenC (7.7%). The introduction of restrictions in late March 2020 led to a 73% reduction in IMD. After the removal of restrictions in 2021, a resurgence in MenB was observed, primarily in teenagers and young adults. During the following winter period (2022/23), MenB disease increased to the highest level since 2012 with cases rising across multiple age groups, however, cases in young children eligible for MenB vaccination remained lower than prior to the pandemic. MenACWY cases remained very low throughout the pandemic period., Conclusions: Once pandemic restrictions in England were removed, MenB quickly rebounded- initially driven by a resurgence in teenagers/young adults, but later among other age groups. MenACWY cases remain very low due to the protection afforded by the adolescent MenACWY conjugate vaccine programme., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AL, AW, JL, LWa, LWi, RB, SAC and XB perform contract research on behalf of UK Health Security Agency for GlaxoSmithKline, Pfizer, and Sanofi Pasteur but receive no personal remuneration. SNL performs contract research on behalf of UK Health Security Agency and St. George’s University of London for vaccine manufacturers but receives no personal remuneration., (Crown Copyright © 2023. Published by Elsevier Ltd. All rights reserved.)

Background: An increase in acute severe hepatitis of unknown aetiology in previously healthy children in the UK in March, 2022, triggered global case-finding. We aimed to describe UK epidemiological investigations of cases and their possible causes., Methods: We actively surveilled unexplained paediatric acute hepatitis (transaminase >500 international units per litre) in children younger than 16 years presenting since Jan 1, 2022, through notifications from paediatricians, microbiologists, and paediatric liver units; we collected demographic, clinical, and exposure information. Then, we did a case-control study to investigate the association between adenoviraemia and other viruses and case-status using multivariable Firth penalised logistic regression. Cases aged 1-10 years and tested for adenovirus were included and compared with controls (ie, children admitted to hospital with an acute non-hepatitis illness who had residual blood samples collected between Jan 1 and May 28, 2022, and without known laboratory-confirmed diagnosis or previous adenovirus testing). Controls were frequency-matched on sex, age band, sample months, and nation or supra-region with randomised selection. We explored temporal associations between frequency of circulating viruses identified through routine laboratory pathogen surveillance and occurrence of cases by linear regression. SARS-CoV-2 seropositivity of cases was examined against residual serum from age-matched clinical comparison groups., Findings: Between Jan 1 and July 4, 2022, 274 cases were identified (median age 3 years [IQR 2-5]). 131 (48%) participants were male, 142 (52%) were female, and one (<1%) participant had sex data unknown. Jaundice (195 [83%] of 235) and gastrointestinal symptoms (202 [91%] of 222) were common. 15 (5%) children required liver transplantation and none died. Adenovirus was detected in 172 (68%) of 252 participants tested, regardless of sample type; 137 (63%) of 218 samples were positive for adenovirus in the blood. For cases that were successfully genotyped, 58 (81%) of 72 had Ad41F, and 57 were identified as positive via blood samples (six of these were among participants who had undergone a transplant). In the case-control analysis, adenoviraemia was associated with hepatitis case-status (adjusted OR 37·4 [95% CI 15·5-90·3]). Increases in the detection of adenovirus from faecal samples, but not other infectious agents, in routine laboratory pathogen surveillance correlated with hepatitis cases 4 weeks later, which independently suggested an association (β 0·06 [95% CI 0·02-0·11]). No association was identified for SARS-CoV-2 antibody seropositivity., Interpretation: We observed an association between adenovirus 41F viraemia and paediatric acute hepatitis. These results can inform diagnostic testing recommendations, clinical management, and exploratory in vitro or clinical studies of paediatric acute hepatitis of unknown aetiology. The role of potential co-factors, including other viruses and host susceptibility, requires further investigation., Funding: None., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)