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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.

Abstract 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.

Ongoing surveillance after pneumococcal conjugate vaccination (PCV) deployment is essential to inform policy decisions and monitor serotype replacement. We report serotype and disease severity trends in 3,719 adults hospitalized for pneumococcal disease in Bristol and Bath, United Kingdom, during 2006–2022. Of those cases, 1,686 were invasive pneumococcal disease (IPD); 1,501 (89.0%) had a known serotype. IPD decreased during the early COVID-19 pandemic but during 2022 gradually returned to prepandemic levels. Disease severity changed throughout this period: CURB65 severity scores and inpatient deaths decreased and ICU admissions increased. PCV7 and PCV13 serotype IPD decreased from 2006–2009 to 2021–2022. However, residual PCV13 serotype IPD remained, representing 21.7% of 2021–2022 cases, indicating that major adult PCV serotype disease still occurs despite 17 years of pediatric PCV use. Percentages of serotype 3 and 8 IPD increased, and 19F and 19A reemerged. In 2020–2022, a total of 68.2% IPD cases were potentially covered by PCV20.

Abstract Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We measure immune responses following Omicron BA.1/2 infection in children aged 6-14 years and relate this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicits a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicits increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primes for robust antibody responses following Omicron infection but these remain primarily focussed against ancestral variants. Primary Omicron infection thus elicits a weak antibody response in children which is boosted after reinfection or vaccination. Cellular responses are robust and broadly equivalent in all groups, providing protection against severe disease irrespective of SARS-CoV-2 variant. Immunological imprinting is likely to act as an important determinant of long-term humoral immunity, the future clinical importance of which is unknown.

Abstract Background Both post-COVID-19 condition (long COVID) and the presence of persisting symptoms that do not meet formal definitions of post-COVID-19-condition may adversely affect quality of life and function. However, their prevalence among children and young people in England is unclear. Methods We used data from repeated surveys in a large cohort of English schoolchildren from the COVID-19 Schools Infection Survey (SIS) for the school year 2021/22 to describe the weighted prevalence of post-COVID-19-condition and compare persisting symptoms between individuals with a positive SARS-CoV-2 test and those with neither a positive test history nor suspected infection. Results Among 7797 children from 173 schools, 1.8% of primary school pupils (aged 4 to 11 years), 4.5% of secondary school pupils in years 7–11 (aged 11 to 16 years) and 6.9% of those in years 12–13 (aged 16 to 18 years) met a definition of post-COVID-19 condition in March 2022. Specific persisting symptoms such as anxiety or difficulty concentrating were frequently reported regardless of prior infection status and increased with age: 48.0% of primary school pupils, 52.9% of secondary school pupils in years 7–11 and 79.5% in years 12–13 reporting at least one symptom lasting more than 12 weeks. Persisting loss of smell and taste, cardiovascular and some systemic symptoms were more frequently reported by those with a previous positive test. Conclusions We showed that ongoing symptoms were frequently reported by English schoolchildren regardless of SARS-CoV-2 test results and some specific symptoms such as loss of smell and taste were more prevalent in those with a positive test history. Our study emphasises the wide-ranging impacts of the COVID-19 pandemic on the health and wellbeing of children and young people.

Vaccination against invasive pneumococcal disease is recommended for older adults but the optimal age group to target has not been determined and may vary by epidemiological setting. Here, the authors use statistical modelling to estimate the optimal ages for vaccination in Brazil, England, Malawi, and South Africa.

IntroductionFollowing the emergence of SARS-CoV-2 in 2020, care homes were disproportionately impacted by high mortality and morbidity of vulnerable elderly residents. Non-pharmaceutical interventions (NPIs) and improved infection control measures together with vaccination campaigns have since improved outcomes of infection. We studied the utility of past infection status, recent vaccination and anti-S antibody titres as possible correlates of protection against a newly emergent Omicron variant infection.MethodsProspective longitudinal surveillance of nine sentinel London care homes from April 2020 onwards found that all experienced COVID-19 outbreaks due to Omicron (BA.1) during December 2021 and January 2022, despite extensive prior SARS-CoV-2 exposure and high COVID-19 vaccination rates, including booster vaccines (>70% residents, >40% staff).ResultsDetailed investigation showed that 46% (133/288) of Omicron BA.1 infections were SARS-CoV-2 reinfections. Two and three COVID-19 vaccine doses were protective against Omicron infection within 2-9 weeks of vaccination, though protection waned from 10 weeks post-vaccination. Prior infection provided additional protection in vaccinated individuals, approximately halving the risk of SARS-CoV-2 infection.DiscussionAnti-S antibody titre showed a dose-dependent protective effect but did not fully account for the protection provided by vaccination or past infection, indicating that other mechanisms of protection are also involved.

Summary: Background: Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of laboratory-confirmed bacterial meningitis in England during 2012–2019. Methods: UK Health Security Agency routinely receives electronic notifications of confirmed infections from National Health Service hospital laboratories in England. Data were extracted for positive bacterial cultures, PCR-positive results for Neisseria meningitidis or Streptococcus pneumoniae from cerebrospinal fluid and positive blood cultures in patients with clinical meningitis. Findings: During 2012–19, there were 6554 laboratory-confirmed cases. Mean annual incidence was 1.49/100,000, which remained stable throughout the surveillance period (p = 0.745). There were 155 different bacterial species identified, including 68.4% (106/1550) Gram-negative and 31.6% (49/155) Gram-positive bacteria. After excluding coagulase-negative staphylococci (2481/6554, 37.9%), the main pathogens causing meningitis were Streptococcus pneumoniae (811/4073, 19.9%), Neisseria meningitidis (497/4073, 12.2%), Staphylococcus aureus (467/4073, 11.5%), Escherichia coli (314/4073, 7.7%) and group B streptococcus (268/4073, 6.6%). Pneumococcal meningitis incidence increased significantly during 2012–9, while meningococcal, group A streptococcal and tuberculous meningitis declined. Infants aged

Abstract Background To update and internally validate a model to predict children and young people (CYP) most likely to experience long COVID (i.e. at least one impairing symptom) 3 months after SARS-CoV-2 PCR testing and to determine whether the impact of predictors differed by SARS-CoV-2 status. Methods Data from a nationally matched cohort of SARS-CoV-2 test-positive and test-negative CYP aged 11–17 years was used. The main outcome measure, long COVID, was defined as one or more impairing symptoms 3 months after PCR testing. Potential pre-specified predictors included SARS-CoV-2 status, sex, age, ethnicity, deprivation, quality of life/functioning (five EQ-5D-Y items), physical and mental health and loneliness (prior to testing) and number of symptoms at testing. The model was developed using logistic regression; performance was assessed using calibration and discrimination measures; internal validation was performed via bootstrapping and the final model was adjusted for overfitting. Results A total of 7139 (3246 test-positives, 3893 test-negatives) completing a questionnaire 3 months post-test were included. 25.2% (817/3246) of SARS-CoV-2 PCR-positives and 18.5% (719/3893) of SARS-CoV-2 PCR-negatives had one or more impairing symptoms 3 months post-test. The final model contained SARS-CoV-2 status, number of symptoms at testing, sex, age, ethnicity, physical and mental health, loneliness and four EQ-5D-Y items before testing. Internal validation showed minimal overfitting with excellent calibration and discrimination measures (optimism-adjusted calibration slope: 0.96575; C-statistic: 0.83130). Conclusions We updated a risk prediction equation to identify those most at risk of long COVID 3 months after a SARS-CoV-2 PCR test which could serve as a useful triage and management tool for CYP during the ongoing pandemic. External validation is required before large-scale implementation.

Abstract Background In England, the emergence the more transmissible SARS-CoV-2 variant Alpha (B.1.1.7) led to a third national lockdown from December 2020, including restricted attendance at schools. Nurseries, however, remained fully open. COVID-19 outbreaks (≥ 2 laboratory-confirmed cases within 14 days) in nurseries were investigated to assess the risk of SARS-CoV-2 infection and cumulative incidence in staff and children over a three-month period when community SARS-CoV-2 infections rates were high and the Alpha variant was spreading rapidly across England. Methods This was a cross-sectional national investigation of COVID-19 outbreaks in nurseries across England. Nurseries reporting a COVID-19 outbreak to PHE between November 2020 and January 2021 were requested to complete a questionnaire about their outbreak. Results Three hundred and twenty-four nurseries, comprising 1% (324/32,852) of nurseries in England, reported a COVID-19 outbreak. Of the 315 (97%) nurseries contacted, 173 (55%) reported 1,657 SARS-CoV-2 cases, including 510 (31%) children and 1,147 (69%) staff. A child was the index case in 45 outbreaks (26%) and staff in 125 (72%) outbreaks. Overall, children had an incidence rate of 3.50% (95%CI, 3.21–3.81%) and was similar irrespective of whether the index case was a child (3.55%; 95%CI, 3.01–4.19%) or staff (3.44%; 95%CI, 3.10–3.82%). Among staff, cumulative incidence was lower if the index case was a child (26.28%; 95%CI, 23.54–29.21%%) compared to a staff member (32.98%; 95%CI, 31.19–34.82%), with the highest cumulative incidence when the index case was also a staff member (37.52%; 95%CI, 35.39–39.70%). Compared to November 2020, outbreak sizes and cumulative incidence was higher in January 2021, when the Alpha variant predominated. Nationally, SARS-CoV-2 infection rates in

During July–December 2021, after COVID-19 restrictions were removed in England, invasive pneumococcal disease incidence in children

Abstract Background Little is known about the views of adolescents returning to secondary school during the current COVID-19 pandemic. Methods In September 2020, the UK Health Security Agency (UKHSA), formerly known as Public Health England (PHE),recruited staff and students in secondary schools to provide nasal swabs, oral fluid and blood samples for SARS-CoV-2 infection and antibody testing. Students aged 11–18 years in five London schools completed a short questionnaire about their perception of the pandemic, returning to school, risk to themselves and to others and infection control measures, and participating in school testing. Results A questionnaire was completed by 64% (297/462) of participants. Students were generally not anxious at all (19.7%; 58/294) or not really anxious (40.0%; 114/295) about returning to school, although 5.4% (n = 16/295) were extremely nervous. Most students were very worried about transmitting the virus to their family (60.2%; 177/294) rather than to other students (22.0%; 65/296) or school staff (19.3%; 57/296), or catching the infection themselves (12.5%; 37/296). Students were more likely to maintain physical distancing in the presence of school staff (84.6%; 247/292) and in public places (79.5%; 233/293) but not when with other students (46.8%; 137/293) or friends (40.8%; 120/294). A greater proportion of younger students (school years 7–9; 11–14-year-olds) reported not being anxious at all than older students (school years 12–13; 16–18-year-olds) (47/174 [27.0%] vs 3/63 [4.8%]; p = 0.001). Younger students were also less likely to adhere to physical distancing measures and wear face masks. Most students reported positive experiences with SARS-CoV-2 testing in schools, with 92.3% (262/284) agreeing to have another blood test in future visits. Conclusions Younger students in secondary schools were less concerned about catching and transmitting SARS-CoV-2 and were less likely to adhere to protective measures. Greater awareness of the potential risks of SARS-CoV-2 transmission between secondary school students potentially leading to increased risk of infection in their teachers and their household members may increase adherence to infection control measures within and outside schools.

Background Little is known about the prevalence and natural trajectory of post-COVID symptoms in young people, despite very high numbers of young people having acute COVID. To date, there has been no prospective follow-up to establish the pattern of symptoms over a 6-month time period. Methods A non-hospitalised, national sample of 3,395 (1,737 SARS-COV-2 Negative;1,658 SARS-COV-2 Positive at baseline) children and young people (CYP) aged 11–17 completed questionnaires 3 and 6 months after PCR-confirmed SARS-CoV-2 infection between January and March 2021 and were compared with age, sex and geographically-matched test-negative CYP. Results Three months after a positive SARS-CoV-2 PCR test, 11 of the 21 most common symptoms reported by >10% of CYP had reduced. There was a further decline at 6 months. By 3 and 6 months the prevalence of chills, fever, myalgia, cough and sore throat of CYP who tested positive for SARS-CoV-2 reduced from 10–25% at testing to Conclusions In CYP, the prevalence of specific symptoms reported at time of PCR-testing declined with time. Similar patterns were observed among test-positives and test-negatives and new symptoms were reported six months post-test for both groups suggesting that symptoms are unlikely to exclusively be a specific consequence of SARS-COV-2 infection. Many CYP experienced unwanted symptoms that warrant investigation and potential intervention.

The UK extended the interval until the second COVID-19 vaccine dose up to 12 weeks. Here, the authors show in a cohort of 750 participants aged 50–89 years that the extended schedule results in higher antibody titers and estimate a higher vaccine effectiveness for the extended schedule.

ObjectivesPaediatric Multisystem Inflammatory Syndrome (PIMS-TS) is a rare life-threatening complication that typically occurs several weeks after SARS-CoV-2 infection in children and young people (CYP). We used national and regional-level data from the COVID-19 pandemic waves in England to develop a model to predict PIMS-TS cases.MethodsSARS-CoV-2 infections in CYP aged 0–15 years in England were estimated using the PHE-Cambridge real-time model. PIMS-TS cases were identified through the British Paediatric Surveillance Unit during (March-June 2020) and through Secondary Uses Services (SUS) from November 2020. A predictive model was developed to estimate PIMS-TS risk and lag times after SARS-CoV-2 infections.ResultsDuring the Alpha wave, the model accurately predicted PIMS-TS cases (506 vs. 502 observed cases), with a median estimated risk of 0.038% (IQR, 0.037–0.041%) of paediatric SARS-CoV-2 infections. For the Delta wave, the median risk of PIMS-TS was significantly lower at 0.026% (IQR, 0.025–0.029%), with 212 observed PIMS-TS cases compared to 450 predicted by the model.ConclusionsThe model accurately predicted national and regional PIMS-TS cases in CYP during the Alpha wave. PIMS-TS cases were 53% lower than predicted during the Delta wave. Further studies are needed to understand the mechanisms of the observed lower risk with the Delta variant.

Summary: Background: There remains uncertainty about the epidemiology of SARS-CoV-2 among school students and staff and the extent to which non-pharmaceutical-interventions reduce the risk of school settings. Methods: We conducted an open cohort study in a sample of 59 primary and 97 secondary schools in 15 English local authority areas that were implementing government guidance to schools open during the pandemic. We estimated SARS-CoV-2 infection prevalence among those attending school, antibody prevalence, and antibody negative to positive conversion rates in staff and students over the school year (November 2020–July 2021). Findings: 22,585 staff and students participated. SARS-CoV-2 infection prevalence among those attending school was highest during the first two rounds of testing in the autumn term, ranging from 0.7% (95% CI 0.2, 1.2) among primary staff in November 2020 to 1.6% (95% CI 0.9, 2.3) among secondary staff in December 2020. Antibody conversion rates were highest in the autumn term. Infection patterns were similar between staff and students, and between primary and secondary schools. The prevalence of nucleoprotein antibodies increased over the year and was lower among students than staff. SARS-CoV-2 infection prevalence in the North-West region was lower among secondary students attending school on normal school days than the regional estimate for secondary school-age children. Interpretation: SARS-CoV-2 infection prevalence in staff and students attending school varied with local community infection rates. Non-pharmaceutical interventions intended to prevent infected individuals attending school may have partially reduced the prevalence of infection among those on the school site. Funding: UK Department of Health and Social Care.

Background: Although 99% of children and young people have been exposed to SARS-CoV-2, the long-term prevalence of post-COVID-19 symptoms in young people is unclear. The aim of this study is to describe symptom profiles 12 months after SARS-CoV-2 testing. Method: A matched cohort study of a national sample of 20,202 children and young people who took a SARS-CoV-2 PCR test between September 2020 and March 2021. Results: 12 months post-index-test, there was a difference in the number of symptoms reported by initial negatives who never tested positive (NN) compared to the other three groups who had at least one positive test (p < 0.001). Similarly, 10.2% of the NN group described five-plus symptoms at 12 months compared to 15.9–24.0% in the other three groups who had at least one positive test. The most common symptoms were tiredness, sleeping difficulties, shortness of breath, and headaches for all four groups. For all these symptoms, the initial test positives with subsequent reports of re-infection had higher prevalences than other positive groups (p < 0.001). Symptom profiles, mental health, well-being, fatigue, and quality of life did not vary by vaccination status. Conclusions: Following the pandemic, many young people, particularly those that have had multiple SARS-CoV-2 positive tests, experience a range of symptoms that warrant consideration and potential investigation and intervention.

Children and adolescents generally experience mild COVID-19. However, those with underlying physical health conditions are at a significantly increased risk of severe disease. Here, we present a comprehensive analysis of antibody and cellular responses in adolescents with severe neuro-disabilities who received COVID-19 vaccination with either ChAdOx1 (n=6) or an mRNA vaccine (mRNA-1273, n=8, BNT162b2, n=1). Strong immune responses were observed after vaccination and antibody levels and neutralisation titres were both higher after two doses. Both measures were also higher after mRNA vaccination and were further enhanced by prior natural infection where one vaccine dose was sufficient to generate peak antibody response. Robust T-cell responses were generated after dual vaccination and were also higher following mRNA vaccination. Early T-cells were characterised by a dominant effector-memory CD4+ T-cell population with a type-1 cytokine signature with additional production of IL-10. Antibody levels were well-maintained for at least 3 months after vaccination and 3 of 4 donors showed measurable neutralisation titres against the Omicron variant. T-cell responses also remained robust, with generation of a central/stem cell memory pool and showed strong reactivity against Omicron spike. These data demonstrate that COVID-19 vaccines display strong immunogenicity in adolescents and that dual vaccination, or single vaccination following prior infection, generate higher immune responses than seen after natural infection and develop activity against Omicron. Initial evidence suggests that mRNA vaccination elicits stronger immune responses than adenoviral delivery, although the latter is also higher than seen in adult populations. COVID-19 vaccines are therefore highly immunogenic in high-risk adolescents and dual vaccination might be able to provide relative protection against the Omicron variant that is currently globally dominant.

Few studies on adult pneumococcal septic arthritis are sufficiently large enough to assess both epidemiological trends following routine pneumococcal immunization and clinical disease. With major shifts in serotypes causing invasive pneumococcal disease (IPD), we wanted to determine the clinical phenotype of adult septic arthritis caused by Streptococcus pneumoniae. We conducted a retrospective cohort study of pneumococcal infections in Bristol and Bath, UK, 2006–2018. We defined pneumococcal septic arthritis as adults with clinically-confirmed septic arthritis, with pneumococcus isolated from sterile-site culture or urinary antigen test positivity. Clinical records were reviewed for each patient in the cohort. Septic arthritis accounted for 1.7% of all IPD cases. 45 cases of adult pneumococcal septic arthritis occurred, with disease typically affecting older adults and those with underlying comorbidity. 67% patients had another focus of infection during their illness. 66% patients required increased care on discharge and 43% had reduced range of movement. In-hospital case fatality rate was 6.7%. One-year patient mortality was 31%. Currently most cases of adult pneumococcal septic arthritis are due to non-PCV13 serotypes which are associated with more severe disease. Non-PCV-13 serotypes had higher prevalence of concomitant pneumococcal infection at another site (73.7% versus 36.6%), increased intensive care or high-dependency unit requirement (32.4% versus 0%), and increased inpatient and 1-year case fatality rate (8.8% versus 0%, and 32.4% versus 27.4% respectively) compared to PCV-13 serotypes. Pneumococcal septic arthritis remains a small proportion of IPD. However, there is significant associated morbidity and mortality, and pneumococcal septic arthritis requires monitoring in coming years.

Summary: Background: The role of educational settings in SARS-CoV-2 infection and transmission remains controversial. We investigated SARS-CoV-2 infection, seroprevalence, and seroconversion rates in secondary schools during the 2020/21 academic year, which included the emergence of the more transmissible alpha and delta variants, in England. Methods: The UK Health Security Agency (UKHSA) initiated prospective surveillance in 18 urban English secondary schools. Participants had nasal swabs for SARS-CoV-2 RT-PCR and blood sampling for SARS-CoV-2 nucleoprotein and spike protein antibodies at the start (Round 1: September-October 2020) and end (Round 2: December 2020) of the autumn term, when schools reopened after national lockdown was imposed in January 2021 (Round 3: March-April 2021), and end of the academic year (Round 4: May-July 2021). Findings: We enrolled 2314 participants (1277 students, 1037 staff; one participant had missing data for PCR testing). In-school testing identified 31 PCR-positive participants (20 students, 11 staff). Another 247 confirmed cases (112 students, 135 staff) were identified after linkage with national surveillance data, giving an overall positivity rate of 12.0% (278/2313; staff: 14.1%, 146/1037 vs students: 10.3%, 132/1276; p = 0.006). Trends were similar to national infection data. Nucleoprotein-antibody seroprevalence increased for students and staff between Rounds 1 and 3 but were similar between Rounds 3 and 4, when the delta variant was the dominant circulating strain. Overall, Nucleoprotein-antibody seroconversion was 18.4% (137/744) in staff and 18.8% (146/778) in students, while Spike-antibody seroconversion was higher in staff (72.8%, 525/721) than students (21.3%, 163/764) because of vaccination. Interpretation: SARS-CoV-2 infection rates in secondary schools remained low when community infection rates were low, even as the delta variant was emerging in England. Funding: This study was funded by the UK Department of Health and Social Care.

ABSTRACT Seroepidemiological studies to monitor antibody kinetics are important for assessing the extent and spread of SARS-CoV-2 in a population. Noninvasive sampling methods are advantageous for reducing the need for venipuncture, which may be a barrier to investigations, particularly in pediatric populations. Oral fluids are obtained by gingiva-crevicular sampling from children and adults and are very well accepted. Enzyme immunoassays (EIAs) based on these samples have acceptable sensitivity and specificity compared to conventional serum-based antibody EIAs and are suitable for population-based surveillance. We describe the development and evaluation of SARS-CoV-2 IgG EIAs using SARS-CoV-2 viral nucleoprotein (NP) and spike (S) proteins in IgG isotype capture format and an indirect receptor-binding-domain (RBD) IgG EIA, intended for use in children as a primary endpoint. All three assays were assessed using a panel of 1,999 paired serum and oral fluids from children and adults participating in school SARS-CoV-2 surveillance studies during and after the first and second pandemic wave in the United Kingdom. The anti-NP IgG capture assay was the best candidate, with an overall sensitivity of 75% (95% confidence interval [CI]: 71 to 79%) and specificity of 99% (95% CI: 78 to 99%) compared with paired serum antibodies. Sensitivity observed in children (80%, 95% CI: 71 to 88%) was higher than that in adults (67%, CI: 60% to 74%). Oral fluid assays (OF) using spike protein and RBD antigens were also 99% specific and achieved reasonable but lower sensitivity in the target population (78%, 95% CI [68% to 86%] and 53%, 95% CI [43% to 64%], respectively). IMPORTANCE We report on the first large-scale assessment of the suitability of oral fluids for detection of SARS-CoV-2 antibody obtained from healthy children attending school. The sample type (gingiva-crevicular fluid, which is a transudate of blood but is not saliva) can be self collected. Although detection of antibodies in oral fluids is less sensitive than that in blood, our study suggests an optimal format for operational use. The laboratory methods we have developed can reliably measure antibodies in children, who are able to take their own samples. Our findings are of immediate practical relevance for use in large-scale seroprevalence studies designed to measure exposure to infection, as they typically require venipuncture. Overall, our data indicate that OF assays based on the detection of SARS-CoV-2 antibodies are a tool suitable for population-based seroepidemiology studies in children and highly acceptable in children and adults, as venipuncture is no longer necessary.

Memory B cells (MBCs) can provide a recall response able to supplement waning antibodies (Abs) with an affinity-matured response better able to neutralize variant viruses. We studied a cohort of elderly care home residents and younger staff (median age of 87 years and 56 years, respectively), who had survived COVID-19 outbreaks with only mild or asymptomatic infection. The cohort was selected because of its high proportion of individuals who had lost neutralizing antibodies (nAbs), thus allowing us to specifically investigate the reserve immunity from SARS-CoV-2–specific MBCs in this setting. Class-switched spike and receptor-binding domain (RBD) tetramer–binding MBCs persisted 5 months after mild or asymptomatic SARS-CoV-2 infection, irrespective of age. The majority of spike- and RBD-specific MBCs had a classical phenotype, but we found that activated MBCs, indicating possible ongoing antigenic stimulation or inflammation, were expanded in the elderly group. Spike- and RBD-specific MBCs remained detectable in the majority of individuals who had lost nAbs, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike-, S1 subunit of the spike protein– (S1-), and RBD-specific recall was also detectable by enzyme-linked immune absorbent spot (ELISPOT) assay in some individuals who had lost nAbs, but was significantly impaired in the elderly. Our findings demonstrate that a reserve of SARS-CoV-2–specific MBCs persists beyond the loss of nAbs but highlight the need for careful monitoring of functional defects in spike- and RBD-specific B cell immunity in the elderly.

University students are a critical group for vaccination programmes against COVID-19, meningococcal disease (MenACWY) and measles, mumps and rubella (MMR). We aimed to evaluate risk factors for vaccine hesitancy and views about on-campus vaccine delivery among university students. Data were obtained through a cross-sectional anonymous online questionnaire study of undergraduate students in June 2021 and analysed by univariate and multivariate tests to detect associations. Complete data were obtained from 827 participants (7.6% response-rate). Self-reporting of COVID-19 vaccine status indicated uptake by two-thirds (64%; 527/827), willing for 23% (194/827), refusal by 5% (40/827) and uncertain results for 8% (66/827). Hesitancy for COVID-19 vaccines was 5% (40/761). COVID-19 vaccine hesitancy was associated with Black ethnicity (aOR, 7.01, 95% CI, 1.8–27.3) and concerns about vaccine side-effects (aOR, 1.72; 95% CI, 1.23–2.39). Uncertainty about vaccine status was frequently observed for MMR (11%) and MenACWY (26%) vaccines. Campus-associated COVID-19 vaccine campaigns were favoured by UK-based students (definitely, 45%; somewhat, 16%) and UK-based international students (definitely, 62%; somewhat, 12%). Limitations of this study were use of use of a cross-sectional approach, self-selection of the response cohort, slight biases in the demographics and a strict definition of vaccine hesitancy. Vaccine hesitancy and uncertainty about vaccine status are concerns for effective vaccine programmes. Extending capabilities of digital platforms for accessing vaccine information and sector-wide implementation of on-campus vaccine delivery are strategies for improving vaccine uptake among students. Future studies of vaccine hesitancy among students should aim to extend our observations to student populations in a wider range of university settings and with broader definitions of vaccine hesitancy.

Background: Older children have higher SARS-CoV-2 infection rates than younger children. We investigated SARS-CoV-2 infection, seroprevalence and seroconversion rates in staff and students following the full reopening of all secondary schools in England. Methods: Public Health England (PHE) invited secondary schools in six regions (East and West London, Hertfordshire, Derbyshire, Manchester and Birmingham) to participate in SARS-CoV-2 surveillance during the 2020/21 academic year. Participants had nasal swabs for RT-PCR and blood samples for SARS-CoV-2 antibodies at the beginning (September 2020) and end (December 2020) of the autumn term. Multivariable logistic regression was used to assess independent risk factors for seropositivity and seroconversion. Findings: Eighteen schools in six regions enrolled 2,209 participants, including 1,189 (53.8%) students and 1,020 (46.2%) staff. SARS-CoV-2 infection rates were not significantly different between students and staff in round one (5/948; [0.53%] vs. 2/876 [0.23%]; p = 0.46) or round two (10/948 [1.05%] vs. 7/886 [0.79%]; p = 0.63), and similar to national prevalence. None of four and 7/15 (47%) sequenced strains in rounds 1 and 2 were the highly transmissible SARS-CoV-2 B.1.1.7 variant. In round 1, antibody seropositivity was higher in students than staff (114/893 [12.8%] vs. 79/861 [9.2%]; p = 0.016), but similar in round 2 (117/893 [13.1%] vs.117/872 [13.3%]; p = 0.85), comparable to local community seroprevalence. Between the two rounds, 8.7% (57/652) staff and 6.6% (36/549) students seroconverted (p = 0.16). Interpretation: In secondary schools, SARS-CoV-2 infection, seropositivity and seroconversion rates were similar in staff and students, and comparable to local community rates. Ongoing surveillance will be important for monitoring the impact of new variants in educational settings.

We evaluated invasive pneumococcal disease (IPD) during 8 years of infant pneumococcal conjugate vaccine (PCV) programs using 10-valent (PCV10) and 13-valent (PCV13) vaccines in 10 countries in Europe. IPD incidence declined during 2011–2014 but increased during 2015–2018 in all age groups. From the 7-valent PCV period to 2018, IPD incidence declined by 42% in children 65 years of age; non-PCV13 serotype incidence increased by 111%, 63%, and 84%, respectively, for these groups. Trends were similar in countries using PCV13 or PCV10, despite different serotype distribution. Serotypes included in the 15-valent PCV represented one third of cases and those in the 20-valent PCVs two thirds of cases in children 65 years of age in 2018. Non-PCV13 serotype increases reduced the overall effect of childhood PCV10/PCV13 programs on IPD. New vaccines providing broader serotype protection are needed.

We describe the effects of the 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines on pneumococcal meningitis in England and Wales during July 1, 2000–June 30, 2016. Overall, 84,473 laboratory-confirmed invasive pneumococcal disease cases, including 4,160 (4.9%) cases with meningitis, occurred. PCV7 implementation in 2006 did not lower overall pneumococcal meningitis incidence because of replacement with non–PCV7-type meningitis incidence. Replacement with PCV13 in 2010, however, led to a 48% reduction in pneumococcal meningitis incidence by 2015–16. The overall case-fatality rate was 17.5%: 10.7% among patients 65 years of age. Serotype 8 was associated with increased odds of death (adjusted odds ratio 2.9, 95% CI 1.8–4.7). In England and Wales, an effect on pneumococcal meningitis was observed only after PCV13 implementation. Further studies are needed to assess pneumococcal meningitis caused by the replacing serotypes.

Abstract Between April 2016 and September 2017, four cases of group B meningococcal disease were reported among sixth-form college students in Bristol, UK. Culture and non-culture whole genome sequencing was utilised and demonstrated that the four genomes of the responsible ST-41 strains clustered closely on a sub-lineage of ST-41/44 clonal complex. The outbreak resulted in two fatalities. A distinct social group associated with one of the cases was selected for vaccination with 4CMenB and pharyngeal swabbing. In vitro culturing, multiple real-time PCR assays (sodC, ctrA and siaD B ) and a PorA PCR-sequencing assay were used to detect meningococcal colonisation and a carriage rate of 32.6% was observed. Furthermore, a high proportion of the pharyngeal swabs (78.3%) yielded a Factor H-Binding Protein (fHbp) nucleotide allele suggesting that the antigenic gene is prevalent among non-meningococcal flora, most likely Neisseria commensals. This may have implications for fHbp as a vaccine antigen should it be shown to influence bacterial colonisation.

Abstract Background To describe patients with inherited and acquired complement deficiency who developed invasive meningococcal disease (IMD) in England over the last decade. Methods Public Health England conducts enhanced surveillance of IMD in England. We retrospectively identified patients with complement deficiency who developed IMD in England during 2008–2017 and retrieved information on their clinical presentation, vaccination status, medication history, recurrence of infection and outcomes, as well as characteristics of the infecting meningococcal strain. Results A total of 16 patients with 20 IMD episodes were identified, including four with two episodes. Six patients had inherited complement deficiencies, two had immune-mediated conditions associated with complement deficiency (glomerulonephritis and vasculitis), and eight others were on Eculizumab therapy, five for paroxysmal nocturnal haemoglobinuria and three for atypical haemolytic uraemic syndrome. Cultures were available for 7 of 11 episodes among those with inherited complement deficiencies/immune-mediated conditions and the predominant capsular group was Y (7/11), followed by B (3/11) and non-groupable (1/11) strains. Among patients receiving Eculizumab therapy, 3 of the 9 episodes were due to group B (3/9), three others were NG but genotypically group B, and one case each of groups E, W and Y. Conclusions In England, complement deficiency is rare among IMD cases and includes inherited disorders of the late complement pathway, immune-mediated disorders associated with low complement levels and patients on Eculizumab therapy. IMD due to capsular group Y predominates in patient with inherited complement deficiency, whilst those on Eculizumab therapy develop IMD due to more diverse capsular groups including non-encapsulated strains.

Background: Invasive Pneumococcal Disease (IPD) is a major public health concern. The effectiveness of 23-valent polysaccharide pneumococcal vaccine (PPV23) against IPD in older age-groups is not fully understood. We measured PPV23 effectiveness against IPD and interpreted changes in IPD incidence between 2000 and 2017. Methods: Public Health England conducts enhanced national IPD surveillance in England and Wales. The indirect cohort method was used to estimate PPV23 effectiveness against IPD in individuals aged ≥65 years eligible for PPV23 vaccination during 2012–2016. IPD incidence in 2016/17 was compared to rates during 2000–2003, when neither PPV23 nor pneumococcal conjugate vaccines (PCVs) were routinely used in England and Wales. Findings: PPV23 effectiveness, irrespective of time since vaccination, was 27% (95% CI, 17–35) after adjusting for age, co-morbidity and year of infection. Vaccine effectiveness reduced non-significantly (p = 0.13) with time since vaccination, from 41% (95% CI, 23–54) for those vaccinated within two years, to 34% (95% CI, 16–48) for those vaccinated 2–4 years previously, and 23% (95% CI, 12–32) for those vaccinated ≥5 years previously. Vaccine effectiveness did not vary significantly by age but was highest in previously healthy individuals (45%; 95%CI, 27–59). IPD incidence for PPV23 serotypes not included in the PCVs did not decrease after routine PPV23 use but increased significantly since PCV introduction in 2006. Interpretation: PPV23 offers moderate short-term protection against IPD in older adults. PPV23 serotypes comprise an increasing proportion of IPD cases in older adults because of serotype replacement following routine PCV use in children. Funding: European Union's Horizon 2020. Keywords: Pneumococcal polysaccharide vaccine, PPV23, Effectiveness, Impact, Broome method, Trends

We observed a sudden and rapid increase in rare invasive pneumococcal disease serotype 7C, from an annual average of 3 cases during 2000–01 through 2015–16 to 29 cases in 2016–17. The increase was caused almost entirely by clonal expansion of sequence type 177, previously associated with vaccine serotype 19F.

Background: The monovalent oral rotavirus vaccine Rotarix® was introduced into the UK infant immunisation programme in 2013. We estimated vaccine effectiveness (VE) in the first two years of the programme. Methods: We used a test-negative case-control design and enhanced national surveillance data for 1869 vaccine-eligible children tested for rotavirus infection to obtain adjusted odds ratios and VE against laboratory-confirmed rotavirus infections. Linked anonymised UK primary care and hospitalisation data from the Clinical Practice Research Datalink (40,723 children) and random-effects Poisson regression were used in a cohort study to estimate VE against all-cause acute gastroenteritis (AGE) and AGE hospitalisations. Results: VE against laboratory-confirmed infection was 69% (95% Confidence Interval: 40–84%) for one dose and 77% (95%CI: 66–85%) for two doses. Two-dose VE in children aged 90% vaccine coverage), explains the lack of VE against all-cause AGE because most AGE in the post-vaccine era would not have been due to rotavirus, although some underestimation of VE could also have occurred due to differential healthcare utilisation by vaccinated and unvaccinated infants. This highlights the importance of using specific vaccine-preventable endpoints for these scenarios. Keywords: Rotavirus, Vaccine effectiveness, Diarrhoea, Gastroenteritis, Electronic health records

Pneumococcal conjugate vaccine (PCV) introduction has reduced pneumococcal meningitis incidence. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project described the serotype distribution of remaining pneumococcal meningitis in countries using PCV10/13 for least 5–7 years with primary series uptake above 70%. The distribution was estimated using a multinomial Dirichlet regression model, stratified by PCV product and age. In PCV10-using sites (N = 8; cases = 1141), PCV10 types caused 5% of cases N = 32; cases = 4503), PCV13 types caused 14% in

Serotype-specific surveillance for invasive pneumococcal disease (IPD) is essential for assessing the impact of 10- and 13-valent pneumococcal conjugate vaccines (PCV10/13). The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project aimed to evaluate the global evidence to estimate the impact of PCV10/13 by age, product, schedule, and syndrome. Here we systematically characterize and summarize the global landscape of routine serotype-specific IPD surveillance in PCV10/13-using countries and describe the subset that are included in PSERENADE. Of 138 countries using PCV10/13 as of 2018, we identified 109 with IPD surveillance systems, 76 of which met PSERENADE data collection eligibility criteria. PSERENADE received data from most (n = 63, 82.9%), yielding 240,639 post-PCV10/13 introduction IPD cases. Pediatric and adult surveillance was represented from all geographic regions but was limited from lower income and high-burden countries. In PSERENADE, 18 sites evaluated PCV10, 42 PCV13, and 17 both; 17 sites used a 3 + 0 schedule, 38 used 2 + 1, 13 used 3 + 1, and 9 used mixed schedules. With such a sizeable and generally representative dataset, PSERENADE will be able to conduct robust analyses to estimate PCV impact and inform policy at national and global levels regarding adult immunization, schedule, and product choice, including for higher valency PCVs on the horizon.

Streptococcus pneumoniae serotype 1 (ST1) was an important cause of invasive pneumococcal disease (IPD) globally before the introduction of pneumococcal conjugate vaccines (PCVs) containing ST1 antigen. The Pneumococcal Serotype Replacement and Distribution Estimation (PSERENADE) project gathered ST1 IPD surveillance data from sites globally and aimed to estimate PCV10/13 impact on ST1 IPD incidence. We estimated ST1 IPD incidence rate ratios (IRRs) comparing the pre-PCV10/13 period to each post-PCV10/13 year by site using a Bayesian multi-level, mixed-effects Poisson regression and all-site IRRs using a linear mixed-effects regression (N = 45 sites). Following PCV10/13 introduction, the incidence rate (IR) of ST1 IPD declined among all ages. After six years of PCV10/13 use, the all-site IRR was 0.05 (95% credibility interval 0.04–0.06) for all ages, 0.05 (0.04–0.05) for

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

Haemophilus influenzae infection causes serious invasive disease, but incidence of the most virulent serotype, Hib, has dropped since introduction of routine Hib vaccination. In England and Wales, the incidence of 2 other serotypes, Hie and Hif, is increasing; during 2001–2010, there was an 11.0% year-on-year increase in Hif and a 7.4% increase in Hie. In 2009–2010, Hif incidence was 0.090/100,000 persons and Hie incidence 0.030/100,000, with higher rates among infants and older adults. Hie had a more severe clinical course; although outcome at 6 months was comparable for the 2 serotypes, case-fatality rate within 7 days of diagnosis was higher for Hie, even after adjustment for age and comorbidities. Multilocus sequence typing revealed a single major circulating clone for both Hif (sequence type 124; 89/99 isolates, 90%) and Hie (sequence type 18; 21/33, 64%), but no association between type and clinical disease or outcome was found.

Enhanced national surveillance for invasive meningococcal disease in England and Wales identified an increase in laboratory-confirmed capsular group Y (MenY) disease from 34 cases in 2007 to 44 in 2008 and 65 in 2009. For cases diagnosed in 2009, patient median age at disease onset was 60 years; 39% of patients had underlying medical conditions, and 19% died. MenY isolates causing invasive disease during 2007–2009 belonged mainly to 1 of 4 clonal complexes (cc), cc23 (56% of isolates), cc174 (21%), cc167 (11%), and cc22 (8%). The 2009 increase resulted primarily from sequence type 1655 (cc23) (22 cases in 2009, compared with 4 cases each in 2007 and 2008). cc23 was associated with lpxL1 mutations and meningitis in younger age groups (65 years). The increase in MenY disease requires careful epidemiologic and molecular monitoring.

We herein present the case of a 15-month-old with visceral leishmaniasis diagnosed in the UK following a short trip to a popular holiday destination in Spain. Four months after the initial symptoms, the diagnosis was made incidentally on microscopy of a bone marrow biopsy taken for suspected haematological malignancy after the child developed hepatosplenomegaly, pancytopaenia, and Klebsiella pneumoniae septicaemia.