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Reinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity, or outcomes of reinfection in children. We aimed to assess the risk of SARS-CoV-2 reinfection in children and compare this with the risk in adults, by analysis of national testing data for England.In our prospective, national surveillance study to assess reinfection of SARS-CoV-2 in children in England, we used national SARS-CoV-2 testing data to estimate the risk of reinfection at least 90 days after primary infection from Jan 27, 2020, to July, 31, 2021, which encompassed the alpha (B.1.1.7) and delta (B.1.617.2) variant waves in England. Data from children up to age 16 years who met the criteria for reinfection were included. Disease severity was assessed by linking reinfection cases to national hospital admission data, intensive care admission, and death registration datasets.Reinfection rates closely followed community infection rates, with a small peak during the alpha wave and a larger peak during the delta wave. In children aged 16 years and younger, 688 418 primary infections and 2343 reinfections were identified. The overall reinfection rate was 66·88 per 100 000 population, which was higher in adults (72·53 per 100 000) than children (21·53 per 100 000). The reinfection rate after primary infection was 0·68% overall, 0·73% in adults compared with 0·18% in children age younger than 5 years, 0·24% in those aged 5-11 years, and 0·49% in those aged 12-16 years. Of the 109 children admitted to hospital with reinfection, 78 (72%) had comorbidities. Hospital admission rates were similar for the first (64 [2·7%] of 2343) and second episode (57 [2·4%] of 2343) and intensive care admissions were rare (seven children for the first episode and four for reinfections). There were 44 deaths within 28 days after primary infection (0·01%) and none after reinfection.The risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the delta variant wave. Children had a lower risk of reinfection than did adults, but reinfections were not associated with more severe disease or fatal outcomes.UK Health Security Agency.

Background There are limited data on immune responses to heterologous COVID–19 immunisation schedules, especially following an extended ≥12–week interval between doses. Methods SARS–CoV–2 infection–naïve and previously–infected adults receiving ChAd–BNT (ChAdOx1 nCoV–19, AstraZeneca followed by BNT162b2, Pfizer–BioNTech) or BNT–ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti–SARS–CoV–2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd–ChAd or BNT–BNT. Results During March–October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously–uninfected adults, S–antibody GMC at 30 days post–second dose were lowest for ChAd–ChAd (862 (95%CI, 694– 1069)) and significantly higher for ChAd–BNT (6233 (5522– 7035); GMR 6.29; (5.04– 7.85); pConclusions These real–world findings demonstrate heterologous schedules with adenoviral–vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.

In August, 2015, the UK implemented an emergency adolescent immunisation programme with the meningococcal ACWY conjugate vaccine to combat a national outbreak of meningococcal group W (MenW) disease due to a hypervirulent ST-11 complex strain, which is currently causing regional and national outbreaks worldwide. This immunisation programme specifically targeted adolescents aged 13-18 years, an age group with low disease incidence but high nasopharyngeal carriage, with the aim of interrupting transmission and providing indirect (herd) protection across the population. Here, we report the impact of the first 4 years of the programme in England.Public Health England conducts meningococcal disease surveillance in England. Laboratory-confirmed cases of invasive meningococcal disease during the academic years 2010-11 to 2014-15 (Sept 1 to Aug 31) were used to predict post-vaccination trends, based on the assumption that cases would plateau 1 year after vaccine implementation (conservative scenario) or that cases would continue to rise for 4 years after vaccine implementation (extreme scenario). Vaccine uptake evaluated in August, 2019, was 37-41% in adolescents aged 18 years immunised in primary care and 71-86% in younger teenagers routinely vaccinated in school. Vaccine effectiveness was estimated with the indirect screening method.MenW and MenY cases plateaued within 12 months and then declined, while MenC cases remained low throughout. Significant reductions were observed among adolescents aged 14-18 years for MenW (incidence rate ratio [IRR] 0·35 [95% CI 0·17-0·76]) and MenY (0·21 [0·07-0·59]) cases, with a non-significant reduction in MenC cases (0·11 [0·01-1·01]). Based on conservative and extreme scenarios, 205-1193 MenW cases were prevented through the indirect effects of the programme and 25 through direct protection. For MenY, an estimated 60-106 cases were prevented through the indirect effects of the programme and 19 through direct protection. Ignoring any residual effect from an earlier MenC-containing vaccine, the overall vaccine effectiveness against MenCWY disease combined was 94% (95% CI 80-99).A meningococcal immunisation programme specifically targeting adolescent carriers succeeded in rapidly controlling a national MenW outbreak, even with moderate initial vaccine uptake.Public Health England.

We investigated a secondary school (11–16 year-olds), a primary school (5–11 year-olds), reception year (4–5 year-olds) and a nursery (2–5 year-olds) following confirmed monkeypox in an adult in each educational setting during June and July 2022. MVA-BN vaccine was offered up to 14 days post exposure to 186 children

Little is known about protection against SARS-CoV-2 infection following previous infection with specific individual SARS-CoV-2 variants, COVID-19 vaccination, and a combination of previous infection and vaccination (hybrid immunity) in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta (B.1.617.2) and omicron (B.1.1.529) variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity.We conducted an observational, test-negative, case-control study using national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England. Symptomatic adolescents aged 12-17 years who were unvaccinated or had received primary BNT162b2 immunisation at symptom onset and had a community SARS-CoV-2 PCR test were included. Vaccination and previous SARS-CoV-2 infection status in adolescents with PCR-confirmed COVID-19 (cases) were compared with vaccination and previous infection status in adolescents who had a negative SARS-CoV-2 PCR test (controls). Vaccination data were collected from the National Immunisation Management System, and were linked to PCR testing data. The primary outcome was protection against SARS-CoV-2 delta and omicron infection (defined as 1 - odds of vaccination or previous infection in cases divided by odds of vaccination or previous infection in controls).Between Aug 9, 2021, and March 31, 2022, 1 161 704 SARS-CoV-2 PCR tests were linked to COVID-19 vaccination status, including 390 467 positive tests with the delta variant and 212 433 positive tests with the omicron variants BA.1 and BA.2. In unvaccinated adolescents, previous SARS-CoV-2 infection with wildtype, alpha (B.1.1.7), or delta strains provided greater protection against subsequent delta infection (86·1%) than against subsequent omicron infection (52·4%); previous delta or omicron infection provided similar protection against omicron reinfection (52·4% [95% CI 50·9-53·8] vs 59·3% [46·7-69·0]). In adolescents with no previous infection, vaccination provided lower protection against omicron infection than against delta infection, with omicron protection peaking at 64·5% (95% CI 63·6-65·4) at 2-14 weeks after dose two and 62·9% (60·5-65·1) at 2-14 weeks after dose three, with waning protection after each dose. Adolescents with hybrid immunity from previous infection and vaccination had the highest protection, irrespective of the SARS-CoV-2 strain in the primary infection. The highest protection against omicron infection was observed in adolescents with vaccination and previous omicron infection, reaching 96·4% (95% CI 84·4-99·1) at 15-24 weeks after vaccine dose two.Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection.None.

Omicron variants of SARS-CoV-2 are globally dominant and infection rates are very high in children. We determined immune responses following Omicron BA.1/2 infection in children aged 6-14 years and related this to prior and subsequent SARS-CoV-2 infection or vaccination. Primary Omicron infection elicited a weak antibody response with poor functional neutralizing antibodies. Subsequent Omicron reinfection or COVID-19 vaccination elicited increased antibody titres with broad neutralisation of Omicron subvariants. Prior pre-Omicron SARS-CoV-2 virus infection or vaccination primed for robust antibody responses following Omicron infection but these remained 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 were 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.

In contrast to the increasing levels of high avidity S antibody measured by the Roche assay in the first 6 months following natural infection, marked waning is seen post 2 or 3 doses of vaccine. Although the kinetics differ between those with vaccine-induced immunity compared to those infected prior to vaccination (hybrid immunity), waning rates appear to be similar following 2 or 3 doses of vaccine. These data should allow countries to optimise the timing of future doses of vaccine.

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.

Serum samples were collected pre- and post-booster vaccination with Comirnaty in 626 participants (aged ≥ 50 years) who had received two Comirnaty doses

Adolescents in the UK were recommended to have their first dose of mRNA vaccine during a period of high community transmission due to the highly transmissible Delta variant, followed by a second dose at an extended interval of 8-12 weeks. We used national SARS-CoV-2 testing, vaccination and hospitalisation data to estimate vaccine effectiveness (VE) using a test-negative case-control design, against PCR-confirmed symptomatic COVID-19 in England. BNT162b2 vaccination in 12-15-year-olds and 16-17-year-olds was associated with lower VE against symptomatic COVID-19 caused by Omicron compared to Delta. Data shows a rapid increase in VE against symptomatic COVID-19 after the second dose for both Delta and Omicron, although this declines to 23% against Omicron after 70+ days. Very high protection was achieved for Delta against hospitalisation after one dose. Our data highlight the importance of the second vaccine dose for protection against symptomatic COVID-19 and raise important questions about the objectives of an adolescent immunisation programme. If prevention of infection is the primary aim, then regular COVID-19 vaccine boosters will be required.

Background Coronavirus Disease 2019 (COVID-19) deaths are rare in children and young people (CYP). The high rates of asymptomatic and mild infections complicate assessment of cause of death in CYP. We assessed the cause of death in all CYP with a positive Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) test since the start of the pandemic in England. Methods and findings CYP aged There were 185 deaths during the 22-month follow-up and 81 (43.8%) were due to COVID-19. Compared to non-COVID-19 deaths in CYP with a positive SARS-CoV-2 test, death due to COVID-19 was independently associated with older age (aOR 1.06 95% confidence interval (CI) 1.01 to 1.11, p = 0.02) and underlying comorbidities (aOR 2.52 95% CI 1.27 to 5.01, p = 0.008), after adjusting for age, sex, ethnicity group, and underlying conditions, with a shorter interval between SARS-CoV-2 testing and death. Half the COVID-19 deaths (41/81, 50.6%) occurred within 7 days of confirmation of SARS-CoV-2 infection and 91% (74/81) within 30 days. Of the COVID-19 deaths, 61 (75.3%) had an underlying condition, especially severe neurodisability (n = 27) and immunocompromising conditions (n = 12). Over the 22-month surveillance period, SARS-CoV-2 was responsible for 1.2% (81/6,790) of all deaths in CYP aged Conclusions COVID-19 deaths remain extremely rare in CYP, with most fatalities occurring within 30 days of infection and in children with specific underlying conditions.

The immune response to SARS-CoV-2 is critical in both controlling primary infection and preventing re-infection. However, there is concern that immune responses following natural infection may not be sustained and that this may predispose to recurrent infection. We analysed the magnitude and phenotype of the SARS-CoV-2 cellular immune response in 100 donors at six months following primary infection and related this to the profile of antibody level against spike, nucleoprotein and RBD over the previous six months. T-cell immune responses to SARS-CoV-2 were present by ELISPOT or ICS analysis in all donors and are characterised by predominant CD4+ T cell responses with strong IL-2 cytokine expression. Median T-cell responses were 50% higher in donors who had experienced an initial symptomatic infection indicating that the severity of primary infection establishes a ‘setpoint’ for cellular immunity that lasts for at least 6 months. The T-cell responses to both spike and nucleoprotein/membrane proteins were strongly correlated with the peak antibody level against each protein. The rate of decline in antibody level varied between individuals and higher levels of nucleoprotein-specific T cells were associated with preservation of NP-specific antibody level although no such correlation was observed in relation to spike-specific responses. In conclusion, our data are reassuring that functional SARS-CoV-2-specific T-cell responses are retained at six months following infection although the magnitude of this response is related to the clinical features of primary 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.

In England, the easing of national lockdown in response to the coronavirus disease 2019 pandemic included the reopening of some primary school years on June 1, 2020. National surveillance did not identify any increase in the year groups attending school. Most children had a severe acute respiratory syndrome coronavirus 2 positive household contact. Hospitalizations for coronavirus disease 2019 were rare, but 2.7% (7/259) had persistent symptoms 1 month later.

Background: The full reopening of schools in September 2020 was associated with an increase in COVID-19 cases and outbreaks in educational settings across England. Methods: Primary and secondary schools reporting an outbreak (≥2 laboratory-confirmed cases within 14 days) to Public Health England (PHE) between 31 August and 18 October 2020 were contacted to complete an online questionnaire. Interpretation: There were 969 primary (n=450) and secondary school outbreaks (n=519) reported to PHE, representing 3% of primary schools and 15% of secondary schools in England. Of the 369 schools contacted, 190 geographically-representative schools completed the questionnaire; 2,425 cases were reported. Secondary school students (1.20%; 95%CI, 1.13-1.28%) had higher attack rates than primary school students (0.84%; 95%CI, 0.75-0.94%). Outbreaks were larger and across more year groups in secondary schools than in primary schools. When an outbreak occurred, attack rates were higher in staff (926/19,083; 4.85%; 95%CI, 4.55-5.17%) than students, especially among primary school teaching staff (378/3852; 9.81%; 95%CI, 8.90-10.82%) compared to secondary school teaching staff (284/7146; 3.97%; 95%CI, 3.79-5.69%). Staff represented 59% (471/799) of cases in primary school outbreaks and 27% (410/1515) in secondary schools (P

Background: Paediatric multisystem inflammatory syndrome temporally associated with SARS-CoV-2 (PIMS-TS), first identified in April 2020, shares features of both Kawasaki disease (KD) and toxic shock syndrome (TSS). Methods: Public Health England initiated prospective national surveillance of PIMS-TS through the British Paediatric Surveillance Unit. Paediatricians were contacted monthly to report PIMS-TS, KD and TSS cases electronically and complete a detailed clinical questionnaire. Cases with symptom onset between 01 March and 15 June 2020 were included. Findings: There were 216 cases with features of PIMS-TS alone, 13 with features of both PIMS-TS and KD, 28 with features of PIMS-TS and TSS and 11 with features of PIMS-TS, KD and TSS, with differences in age, ethnicity, clinical presentation and disease severity between the three phenotypic groups. There was a strong geographical and temporal association between SARS-CoV-2 infection rates and PIMS-TS cases. Of those tested, 14·8% (39/264) children had a positive SARS-CoV-2 RT-PCR, and 63·6% (75/118) were positive for SARS-CoV-2 serology. In total 118 children (44·0%) required intensive care, which was more common in cases with a TSS phenotype: 89/216 (41·2%) with PIMS-TS only vs. 19/28 (67·9%) with PIMS-TS/TSS and 6/11 (54·5%) with PIMS-TS/KD/TSS. Three of five children with cardiac arrest had PIMS-TS/TSS phenotype. Three children (1·1%) died. Interpretation: The strong association between SARS-CoV-2 infection and PIMS-TS emphasises the importance of maintaining low community infection rates to reduce the risk of this rare but severe complication in children and adolescents. Close follow-up will be important to monitor long-term complications in children with PIMS-TS. Funding: PHE Declaration of Interests: None to declare. Ethics Approval Statement: PHE has legal permission under Regulation 3 of The Health Service (Control of Patient Information) Regulations 2002, to conduct national surveillance of communicable diseases in England and, as such, individual patient consent is not required. Public Health Wales, through the established order legislation, is required to conduct surveillance of communicable diseases in Wales and, as such, individual patient consent is not required. The surveillance protocol was approved by the Public Benefit and Privacy Panel for Health and Social Care in Scotland (Ref: 2021-0041, 19th May 2020).

BackgroundReinfection after primary SARS-CoV-2 infection is uncommon in adults, but little is known about the risks, characteristics, severity or outcomes of reinfection in children.MethodsWe used national SARS-CoV-2 testing data in England to estimate the risk of reinfection ≥90 days after primary infection from 01 January 2020 to 31 July 2021, which encompassed both the Alpha and Delta waves in England. Disease severity was assessed by linking reinfection cases to national hospitalisation, intensive care admission and death registrations datasets.FindingsReinfection rates closely followed community infection rates, with a small peak during the Alpha wave and a larger peak during the Delta wave. In children aged ≤16 years, there were 688,418 primary infections and 2,343 reinfections. The overall reinfection rate was 66·88/100,000 population, being higher in adults (72.53/100,000) than in children (21·53/100,000). Reinfection rates after primary infection were 0·68% overall, 0·73% in adults and 0·34% in children. Of the 109 reinfections in children admitted to hospital, 78 (72%) had underlying comorbidities. Hospitalisation rates were similar for the first (64/2343, 2·73%) and second episode (57/2343, 2·43%). Intensive care admission was rare after primary infection (n=7) or reinfection (n=4), mainly in children with comorbidities. 44 deaths occurred after primary infection within 28 days of diagnosis (44/688,418, 0·01%), none after possible reinfections.InterpretationThe risk of SARS-CoV-2 reinfection is strongly related to exposure due to community infection rates, especially during the Delta variant wave. Children had a lower risk of reinfection than adults, but reinfections were not associated with more severe disease or fatal outcomes.FundingPHE/UKHSAResearch in ContextEvidence Before this studyWe searched PubMed with the terms “COVID-19” or “SARS-CoV-2” with “reinfection” to identify publications relating to SARS-CoV-2 reinfections from 01 January until 15 November 2021. There were few publications relating to SARS-CoV-2 reinfections, and these primarily related to adults. Published studies reported very low rates of reinfection during the first few months after primary infection in adults. COVID-19 vaccines provide effective immune protection against SARS-CoV-2 infection, but recent studies have reported increasing risk of breakthrough infection with time since primary vaccination due to waning immunity. Several SARS-CoV-2 variants, including the beta, gamma and delta variants have been shown to partially evade immunity after natural infection and vaccination, potentially increasing the risk of reinfections and breakthrough infections, respectively. Data on reinfections in children are lacking and restricted mainly to case reports in immunocompromised children.Added Value of This StudyWe used national SARS-CoV-2 testing data during the first 19 months of the pandemic to estimate the risk of reinfection in children compared to adults during a period that encompassed both the Alpha and the Delta variant waves in England. We found that the risk of reinfection correlated with the risk of SARS-CoV-2 exposure and therefore, closely reflected community infection rates, with most reinfections occurring during the Delta variant wave. Whilst acknowledging the limitation of using national testing data, we found that children had a lower risk of reinfection compared to adults and that the risk of reinfection in children increased with age. Reinfections were not associated with severe disease in terms of hospitalization or intensive care admission and there were no fatalities within 28 days of the reinfection episode in children.Implications of all the Available EvidenceSARS-CoV-2 reinfections are rare in children, especially younger children, and occurred mainly during the Delta wave in England. Reinfections were not associated with more severe disease or fatal outcomes in children. COVID-19 vaccination will provide further protection against primary infections and reinfections in children.

Timely vaccination is critical for providing early protection against meningococcal B (MenB) disease because of the high incidence in early childhood. We assessed the timeliness of vaccination in children with confirmed MenB disease after 4CMenB (a recombinant protein-based vaccine) implementation into the national infant immunisation programme in England.Public Health England (PHE) conducts surveillance of invasive meningococcal disease (IMD) in England. Children born since 01 July 2015 who developed MenB disease between 01 September 2015 and 31 August 2019 (four surveillance years) were included in the analysis.There were 276 children with laboratory-confirmed MenB disease, including 36 infants who were too young for vaccination, 59 who were eligible for one 4CMenB dose, 104 for two doses and 77 for 3 doses before they developed MenB disease. Prior to developing MenB disease, there were 59 opportunities for vaccination with two 4CMenB doses in 48/104 (46.5%) eligible infants and 41 opportunities in 28/77 (36.6%) children aged ≥ 1 year who were under-immunised. A schedule with a shorter interval at 8 and 12 weeks of age, compared to the current schedule at 8 and 16 weeks, had the potential to offer an additional 4CMenB dose to 35/58 infants (58.6%) who developed MenB disease between 10 and 18 weeks of age.A high proportion of infants and toddlers with laboratory-confirmed MenB disease had not received their scheduled 4CMenB vaccine prior to developing MenB disease. An infant priming schedule with a shorter interval of 4 weeks has the potential to provide earlier protection against MenB disease.