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.

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.

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.

Children develop robust and sustained cross-reactive spike-specific immune responses to SARS-CoV-2 infection.

SARS-CoV-2 infection is generally mild or asymptomatic in children but a biological basis for this outcome is unclear. Here we compare antibody and cellular immunity in children (aged 3-11 years) and adults. Antibody responses against spike protein were high in children and seroconversion boosted responses against seasonal Beta-coronaviruses through cross-recognition of the S2 domain. Neutralization of viral variants was comparable between children and adults. Spike-specific T cell responses were more than twice as high in children and were also detected in many seronegative children, indicating pre-existing cross-reactive responses to seasonal coronaviruses. Importantly, children retained antibody and cellular responses 6 months after infection, whereas relative waning occurred in adults. Spike-specific responses were also broadly stable beyond 12 months. Therefore, children generate robust, cross-reactive and sustained immune responses to SARS-CoV-2 with focused specificity for the spike protein. These findings provide insight into the relative clinical protection that occurs in most children and might help to guide the design of pediatric vaccination regimens.

Emergence of SARS-CoV-2 Alpha (B.1.1.7) variant, infection rates, antibody seroconversion and seroprevalence rates in secondary school students and staff: Active prospective surveillance, December 2020 to March 2021, England.

OBJECTIVES: We assessed SARS-CoV-2 infection, seroprevalence and seroconversion in students and staff when secondary schools reopened in March 2021. METHODS: We initiated SARS-CoV-2 surveillance in 18 secondary schools across six regions in September 2020. Participants provided 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 and at the start of the spring term (March 2021). FINDINGS: In March 2021, 1895 participants (1100 students:795 staff) were tested; 5.6% (61/1094) students and 4.4% (35/792) staff had laboratory-confirmed SARS-CoV-2 infection from December 2020-March 2021. Nucleoprotein-antibody seroprevalence was 36.3% (370/1018) in students and 31.9% (245/769) in staff, while spike-antibody prevalence was 39.5% (402/1018) and 59.8% (459/769), respectively, similar to regional community seroprevalence. Between December 2020 and March 2021, 14.8% (97/656; 95%CI: 12.2-17.7) students and 10.0% (59/590; 95%CI: 7.7-12.7) staff seroconverted. Weekly seroconversion rates were similar from September to December 2020 (8.0/1000) and from December 2020 to March 2021 (7.9/1000; students: 9.3/1,000; staff: 6.3/1,000). INTERPRETATION: By March 2021, a third of secondary school students and staff had evidence of prior infection based on N-antibody seropositivity, and an additional third of staff had evidence of vaccine-induced immunity based on S-antibody seropositivity.

Antibody persistence and neutralising activity in primary school students and staff: Prospective active surveillance, June to December 2020, England.

BACKGROUND: Prospective, longitudinal SARS-CoV-2 sero-surveillance in schools across England was initiated after the first national lockdown, allowing comparison of child and adult antibody responses over time. METHODS: Prospective active serological surveillance in 46 primary schools in England tested for SARS-CoV-2 antibodies during June, July and December 2020. Samples were tested for nucleocapsid (N) and receptor binding domain (RBD) antibodies, to estimate antibody persistence at least 6 months after infection, and for the correlation of N, RBD and live virus neutralising activity. FINDINGS: In June 2020, 1,344 staff and 835 students were tested. Overall, 11.5% (95%CI: 9.4-13.9) and 11.3% (95%CI: 9.2-13.6; p = 0.88) of students had nucleoprotein and RBD antibodies, compared to 15.6% (95%CI: 13.7-17.6) and 15.3% (95%CI: 13.4-17.3; p = 0.83) of staff. Live virus neutralising activity was detected in 79.8% (n = 71/89) of nucleocapsid and 85.5% (71/83) of RBD antibody positive children. RBD antibodies correlated more strongly with neutralising antibodies (rs=0.7527; p<0.0001) than nucleocapsid antibodies (rs=0.3698; p<0.0001). A median of 24.4 weeks later, 58.2% (107/184) participants had nucleocapsid antibody seroreversion, compared to 20.9% (33/158) for RBD (p<0.001). Similar seroreversion rates were observed between staff and students for nucleocapsid (p = 0.26) and RBD-antibodies (p = 0.43). Nucleocapsid and RBD antibody quantitative results were significantly lower in staff compared to students (p = 0.028 and <0.0001 respectively) at baseline, but not at 24 weeks (p = 0.16 and p = 0.37, respectively). INTERPRETATION: The immune response in children following SARS-CoV-2 infection was robust and sustained (>6 months) but further work is required to understand the extent to which this protects against reinfection.

Feasibility and acceptability of SARS-CoV-2 testing and surveillance in primary school children in England: Prospective, cross-sectional study.

BACKGROUND: The reopening of schools during the COVID-19 pandemic has raised concerns about widespread infection and transmission of SARS-CoV-2 in educational settings. In June 2020, Public Health England (PHE) initiated prospective national surveillance of SARS-CoV-2 in primary schools across England (sKIDs). We used this opportunity to assess the feasibility and agreeability of large-scale surveillance and testing for SARS-CoV-2 infections in school among staff, parents and students. METHODS: Staff and students in 131 primary schools were asked to complete a questionnaire at recruitment and provide weekly nasal swabs for SARS-CoV-2 RT-PCR testing (n = 86) or swabs with blood samples for antibody testing (n = 45) at the beginning and end the summer half-term. In six blood sampling schools, students were asked to complete a pictorial questionnaire before and after their investigations. RESULTS: In total, 135 children aged 4-7 years (n = 40) or 8-11 years (n = 95) completed the pictorial questionnaire fully or partially. Prior to sampling, oral fluid sampling was the most acceptable test (107/132, 81%) followed by throat swabs (80/134, 59%), nose swabs (77/132, 58%), and blood tests (48/130, 37%). Younger students were more nervous about all tests than older students but, after completing their tests, most children reported a "better than expected" experience with all the investigations. Students were more likely to agree to additional testing for nose swabs (93/113, 82%) and oral fluid (93/114, 82%), followed by throat swabs (85/113, 75%) and blood tests (72/108, 67%). Parents (n = 3,994) and staff (n = 2,580) selected a preference for weekly testing with nose swabs, throat swabs or oral fluid sampling, although staff were more flexible about testing frequency. CONCLUSIONS: Primary school staff and parents were supportive of regular tests for SARS-CoV-2 and selected a preference for weekly testing. Children preferred nose swabs and oral fluids over throat swabs or blood sampling.

SARS-CoV-2 infection, antibody positivity and seroconversion rates in staff and students following full reopening of secondary schools in England: A prospective cohort study, September-December 2020.

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.