Paediatric acute hepatitis of unknown aetiology: a national investigation and adenoviraemia case-control study in the UK.

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 (ß 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.

Factors associated with COVID-19 vaccine uptake in adolescents: a national cross-sectional study, August 2021-January 2022, England.

OBJECTIVES: To assess socioeconomic and geographical factors associated with COVID-19 vaccine uptake in pupils attending state-funded secondary schools in England. DESIGN: Cross-sectional observational study. SETTING: State-funded schools in England. PARTICIPANTS: Pupils aged 12-17 years attending state-funded schools in England for the academic year 2021/2022. OUTCOME MEASURES: Demographic, socioeconomic and geographical factors associated with vaccination uptake. We linked individual-level data from the English Schools Census to the National Immunisation Management System to obtain COVID-19 vaccination status of 3.2 million adolescents. We used multivariable logistic regression to assess demographic, socioeconomic and geographical factors associated with vaccination. RESULTS: By 9 January 2022, 56.8% of adolescents aged 12-17 years old had received at least one dose, with uptake increasing from 48.7% in those aged 12 years old to 77.2% in those aged 17 years old. Among adolescents aged 12-15 years old, there were large variations in vaccine uptake by region and ethnic group. Pupils who spoke English as an additional language (38.2% vs 55.5%), with special educational needs (48.1% vs 53.5%), eligible for free school meals (35.9% vs 58.9%) and lived in more deprived areas (36.1% in most deprived vs 70.3% in least deprived) had lower vaccine uptake. Socioeconomic variables had greater impact on the odds of being vaccinated than geographical variables. School-level analysis found wide variation in vaccine uptake between schools even within the same region. Schools with higher proportions of pupils eligible for free school meals had lower vaccine uptake. CONCLUSIONS: We found large differences in vaccine uptake by geographical region and ethnicity. Socioeconomic variables had a greater impact on the odds of being vaccinated than geographical variables. Further research is required to identify evidence-based interventions to improve vaccine uptake in adolescents.

SARS-CoV-2-specific immune responses and clinical outcomes after COVID-19 vaccination in patients with immune-suppressive disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune responses and infection outcomes were evaluated in 2,686 patients with varying immune-suppressive disease states after administration of two Coronavirus Disease 2019 (COVID-19) vaccines. Overall, 255 of 2,204 (12%) patients failed to develop anti-spike antibodies, with an additional 600 of 2,204 (27%) patients generating low levels (<380 AU ml-1). Vaccine failure rates were highest in ANCA-associated vasculitis on rituximab (21/29, 72%), hemodialysis on immunosuppressive therapy (6/30, 20%) and solid organ transplant recipients (20/81, 25% and 141/458, 31%). SARS-CoV-2-specific T cell responses were detected in 513 of 580 (88%) patients, with lower T cell magnitude or proportion in hemodialysis, allogeneic hematopoietic stem cell transplantation and liver transplant recipients (versus healthy controls). Humoral responses against Omicron (BA.1) were reduced, although cross-reactive T cell responses were sustained in all participants for whom these data were available. BNT162b2 was associated with higher antibody but lower cellular responses compared to ChAdOx1 nCoV-19 vaccination. We report 474 SARS-CoV-2 infection episodes, including 48 individuals with hospitalization or death from COVID-19. Decreased magnitude of both the serological and the T cell response was associated with severe COVID-19. Overall, we identified clinical phenotypes that may benefit from targeted COVID-19 therapeutic strategies.

Immunological imprinting of humoral immunity to SARS-CoV-2 in children.

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.

Post-COVID-19 condition and persisting symptoms in English schoolchildren: repeated surveys to March 2022.

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.

Antibody Persistence After Primary SARS-CoV-2 Infection and Protection Against Future Variants Including Omicron in Adolescents: National, Prospective Cohort Study.

BACKGROUND: Antibodies are a measure of immunity after primary infection, which may help protect against further SARS-CoV-2 infections. They may also provide some cross-protection against SARS-CoV-2 variants. There are limited data on antibody persistence and, especially, cross-reactivity against different SARS-CoV-2 variants after primary infection in children. METHODS: We initiated enhanced surveillance in 18 secondary schools to monitor SARS-CoV-2 infection and transmission in September 2020. Students and Staff provided longitudinal blood samples to test for variant-specific SARS-CoV-2 antibodies using in-house receptor binding domain assays. We recruited 1189 students and 1020 staff; 160 (97 students, 63 staff) were SARS-CoV-2 nucleocapsid-antibody positive at baseline and had sufficient serum for further analysis. RESULTS: Most participants developed sustained antibodies against their infecting [wild-type (WT)] strain as well as cross-reactive antibodies against the Alpha, Beta and Delta variants but at lower titers than WT. Staff had significantly lower antibodies titers against WT as cross-reactive antibodies against the Alpha, Beta and Delta variants than students (all P < 0.01). In participants with sufficient sera, only 2.3% (1/43) students and 17.2% (5/29) staff had cross-reactive antibodies against the Omicron variant; they also had higher antibody titers against WT (3042.5; 95% confidence interval: 769.0-12,036.2) than those who did not have cross-reactive antibodies against the Omicron variant (680.7; 534.2-867.4). CONCLUSIONS: We found very high rates of antibody persistence after primary infection with WT in students and staff. Infection with WT induced cross-reactive antibodies against Alpha, Beta and Delta variants, but not Omicron. Primary infection with WT may not be cross-protective against the Omicron variant.

National and regional prevalence of SARS-CoV-2 antibodies in primary and secondary school children in England: the School Infection Survey, a national open cohort study, November 2021SARS-CoV-2 antibody prevalence in school children.

BACKGROUND: SARS-CoV-2 infection rates are likely to be underestimated in children because of asymptomatic or mild infections. We aim to estimate national and regional prevalence of SARS-CoV-2 antibodies in primary (4-11 years old) and secondary (11-18 years old) school children between 10 November and 10 December 2021. METHODS: Cross-sectional surveillance in England using two-stage sampling, firstly stratifying into regions and selecting local authorities, then selecting schools according to a stratified sample within selected local authorities. Participants were sampled using a novel oral fluid-validated assay for SARS-CoV-2 spike and nucleocapsid IgG antibodies. RESULTS: 4980 students from 117 state-funded schools (2706 from 83 primary schools, 2274 from 34 secondary schools) provided a valid sample. After weighting for age, sex, and ethnicity, and adjusting for assay accuracy, the national prevalence of SARS-CoV-2 antibodies in primary school students, who were all unvaccinated, was 40.1% (95% CI 37.3-43.0). Antibody prevalence increased with age (p < 0.001) and was higher in urban than rural schools (p = 0.01). In secondary school students, the adjusted, weighted national prevalence of SARS-CoV-2 antibodies was 82.4% (95% CI 79.5-85.1); including 71.5% (95% CI 65.7-76.8) in unvaccinated and 97.5% (95% CI 96.1-98.5) in vaccinated students. Antibody prevalence increased with age (p < 0.001), and was not significantly different in urban versus rural students (p = 0.1). CONCLUSIONS: In November 2021, using a validated oral fluid assay, national SARS-CoV-2 seroprevalence was estimated to be 40.1% in primary school students and 82.4% in secondary school students. In unvaccinated children, this was approximately threefold higher than confirmed infections highlighting the importance of seroprevalence studies to estimate prior exposure. DATA AVAILABILITY: Deidentified study data are available for access by accredited researchers in the ONS Secure Research Service (SRS) for accredited research purposes under part 5, chapter 5 of the Digital Economy Act 2017. For further information about accreditation, contact Research.support@ons.gov.uk or visit the SRS website.

Risk factors for SARS-CoV-2 infection in primary and secondary school students and staff in England in the 2020/2021 school year: a longitudinal study.

OBJECTIVES: Investigate risk factors for SARS-CoV-2 infections in school students and staff. METHODS: In the 2020/2021 school year, we administered polymerase chain reaction, antibody tests, and questionnaires to a sample of primary and secondary school students and staff, with data linkage to COVID-19 surveillance. We fitted logistic regression models to identify the factors associated with infection. RESULTS: We included 6799 students and 5090 staff in the autumn and 11,952 students and 4569 staff in the spring/summer terms. Infections in students in autumn 2020 were related to the percentage of students eligible for free school meals. We found no statistical association between infection risk in primary and secondary schools and reported contact patterns between students and staff in either period in our study. Using public transports was associated with increased risk in autumn in students (adjusted odds ratio = 1.72; 95% confidence interval 1.31-2.25) and staff. One or more infections in the same household during either period was the strongest risk factor for infection in students and more so among staff. CONCLUSION: Deprivation, community, and household factors were more strongly associated with infection than contacts patterns at school; this suggests that the additional school-based mitigation measures in England in 2020/2021 likely helped reduce transmission risk in schools.

Association of Spike-Specific T Cells With Relative Protection From Subsequent SARS-CoV-2 Omicron Infection in Young Children.

This cohort study investigates the risk of SARS-CoV-2 reinfection among young children with and without spike-specific T-cell responses.

Implementation of COVID-19 Preventive Measures and Staff Well-Being in a Sample of English Schools 2020-2021.

BACKGROUND: We examined fidelity and feasibility of implementation of COVID-19 preventive measures in schools, and explored associations between adherence to these measures and staff well-being, to inform policy on sustainable implementation and staff wellbeing. METHODS: Surveys were conducted across 128 schools in England with 107 headteachers and 2698 staff-members with reference to autumn term 2020, examining school-level implementation of preventive measures, adherence, and teacher burnout (response rates for headteacher and staff surveys were 84% and 59%, respectively). RESULTS: The median number of measures implemented in primary and secondary schools was 33 (range 23-41), and 32 (range 22-40), respectively; most measures presented challenges. No differences were found regarding number of measures implemented by school-level socio-economic disadvantage. High adherence was reported for staff wearing face-coverings, staff regularly washing their hands, (secondary only) desks facing forwards, and (primary only) increased cleaning of surfaces and student hand-washing. Adherence to most measures was reported as higher in primary than secondary schools. Over half of school leaders and 42% (517/1234) of other teaching staff suffered from high emotional exhaustion. Higher teacher-reported school-wide adherence with measures was consistently associated with lower burnout for leaders and other teaching staff. CONCLUSIONS: Findings indicate a tremendous effort in implementing preventive measures and an urgent need to support investments in improving teacher wellbeing.

Parents' and teachers' attitudes to and experiences of the implementation of COVID-19 preventive measures in primary and secondary schools following reopening of schools in autumn 2020: a descriptive cross-sectional survey.

OBJECTIVE: To assess implementation and ease of implementation of control measures in schools as reported by staff and parents. DESIGN: A descriptive cross-sectional survey. SETTING: Staff and parents/guardians of the 132 primary schools and 19 secondary schools participating in COVID-19 surveillance in school kids (sKIDs and sKIDsPLUS Studies). MAIN OUTCOME MEASURE: Prevalence of control measures implemented in schools in autumn 2020, parental and staff perception of ease of implementation. RESULTS: In total, 56 of 151 (37%) schools participated in this study, with 1953 parents and 986 staff members completing the questionnaire. Most common measures implemented by schools included regular hand cleaning for students (52 of 56, 93%) and staff (70 of 73, 96%), as reported by parents and staff, respectively, and was among the easiest to implement at all times for students (57%) and even more so, for staff (78%). Maintaining 2-metre distancing was less commonly reported for students (24%-51%) as it was for staff (81%-84%), but was one of the most difficult to follow at all times for students (25%) and staff (16%) alike. Some measures were more commonly reported by primary school compared to secondary school parents, including keeping students within the same small groups (28 of 41, 68% vs 8 of 15, 53%), ensuring the same teacher for classes (29 of 41, 71% vs 6 of 15, 40%). On the other hand, wearing a face covering while at school was reported by three-quarters of secondary school parents compared with only parents of 4 of 41 (10%) primary schools. Other measures such as student temperature checks (5%-13%) and advising staff work from home if otherwise healthy (7%-15%) were rarely reported. CONCLUSIONS: Variable implementation of infection control measures was reported, with some easier to implement (hand hygiene) than others (physical distancing).

Epidemiology of SARS-CoV-2 infection among staff and students in a cohort of English primary and secondary schools during 2020-2021.

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.

Perceptions of adolescents on the COVID-19 pandemic and returning to school: qualitative questionnaire survey, September 2020, England.

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.

mRNA or ChAd0x1 COVID-19 Vaccination of Adolescents Induces Robust Antibody and Cellular Responses With Continued Recognition of Omicron Following mRNA-1273.

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.

The COVID-19 Schools Infection Survey in England: Protocol and Participation Profile for a Prospective Observational Cohort Study.

BACKGROUND: One of the most debated questions in the COVID-19 pandemic has been the role of schools in SARS-CoV-2 transmission. The COVID-19 Schools Infection Survey (SIS) aims to provide much-needed evidence addressing this issue. OBJECTIVE: We present the study protocol and participation profile for the SIS study, aimed at assessing the role of schools in SARS-CoV-2 infection and transmission within school settings, and investigating how transmission within and from schools could be mitigated through the implementation of school COVID-19 control measures. METHODS: SIS was a multisite, prospective, observational cohort study conducted in a stratified random sample of primary and secondary schools in selected local authorities in England. A total of 6 biobehavioral surveys were planned among participating students and staff during the 2020-2021 academic year, between November 2020 and July 2021. Key measurements were SARS-CoV-2 virus prevalence, assessed by nasal swab polymerase chain reaction; anti-SARS-CoV-2 (nucleocapsid protein) antibody prevalence and conversion, assessed in finger-prick blood for staff and oral fluid for students; student and staff school attendance rates; feasibility and acceptability of school-level implementation of SARS-CoV-2 control measures; and investigation of selected school outbreaks. The study was approved by the United Kingdom Health Security Agency Research Support and Governance Office (NR0237) and London School of Hygiene & Tropical Medicine Ethics Review Committee (reference 22657). RESULTS: Data collection and laboratory analyses were completed by September 2021. A total of 22,585 individuals-1891 staff and 4654 students from 59 primary schools and 5852 staff and 10,188 students from 97 secondary schools-participated in at least one survey. Across all survey rounds, staff and student participation rates were 45.2% and 16.4%, respectively, in primary schools and 30% and 15.2%, respectively, in secondary schools. Although primary student participation increased over time, and secondary student participation remained reasonably consistent, staff participation declined across rounds, especially for secondary school staff (3165/7583, 41.7% in round 1 and 2290/10,374, 22.1% in round 6). Although staff participation overall was generally reflective of the eligible staff population, student participation was higher in schools with low absenteeism, a lower proportion of students eligible for free school meals, and from schools in the least deprived locations (in primary schools, 446/4654, 9.6% of participating students were from schools in the least deprived quintile compared with 1262/22,225, 5.7% of eligible students). CONCLUSIONS: We outline the study design, methods, and participation, and reflect on the strengths of the SIS study as well as the practical challenges encountered and the strategies implemented to address these challenges. The SIS study, by measuring current and incident infection over time, alongside the implementation of control measures in schools across a range of settings in England, aims to inform national guidance and public health policy for educational settings. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/34075.

Emergence of the delta variant and risk of SARS-CoV-2 infection in secondary school students and staff: Prospective surveillance in 18 schools, England.

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.

Secondary attack rates in primary and secondary school bubbles following a confirmed case: Active, prospective national surveillance, November to December 2020, England.

BACKGROUND: Following the full re-opening of schools in England and emergence of the SARS-CoV-2 Alpha variant, we investigated the risk of SARS-CoV-2 infection in students and staff who were contacts of a confirmed case in a school bubble (school groupings with limited interactions), along with their household members. METHODS: Primary and secondary school bubbles were recruited into sKIDsBUBBLE after being sent home to self-isolate following a confirmed case of COVID-19 in the bubble. Bubble participants and their household members were sent home-testing kits comprising nasal swabs for RT-PCR testing and whole genome sequencing, and oral fluid swabs for SARS-CoV-2 antibodies. RESULTS: During November-December 2020, 14 bubbles were recruited from 7 schools, including 269 bubble contacts (248 students, 21 staff) and 823 household contacts (524 adults, 299 children). The secondary attack rate was 10.0% (6/60) in primary and 3.9% (4/102) in secondary school students, compared to 6.3% (1/16) and 0% (0/1) among staff, respectively. The incidence rate for household contacts of primary school students was 6.6% (12/183) and 3.7% (1/27) for household contacts of primary school staff. In secondary schools, this was 3.5% (11/317) and 0% (0/1), respectively. Household contacts were more likely to test positive if their bubble contact tested positive although there were new infections among household contacts of uninfected bubble contacts. INTERPRETATION: Compared to other institutional settings, the overall risk of secondary infection in school bubbles and their household contacts was low. Our findings are important for developing evidence-based infection prevention guidelines for educational settings.

Serological responses to COVID-19 Comirnaty booster vaccine, London, United Kingdom, September to December 2021.

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses < 30 days apart, two Comirnaty doses ≥ 30 days apart or two Vaxzevria doses ≥ 30 days apart. Irrespective of primary vaccine type or schedule, spike antibody GMTs peaked 2-4 weeks after second dose, fell significantly ≤ 38 weeks later and rose above primary immunisation GMTs 2-4 weeks post-booster. Higher post-booster responses were observed with a longer interval between primary immunisation and boosting.