Effectiveness of Autumn 2023 COVID-19 vaccination and residual protection of prior doses against hospitalisation in England, estimated using a test-negative case-control study.

INTRODUCTION: The last COVID-19 vaccine offered to all adults in England became available from November 2021. The most recent booster programme commenced in September 2023. Bivalent BA.4-5 or monovalent XBB.1.5 boosters were given. During the study period, the JN.1 variant became dominant in England. METHODS: Vaccine effectiveness against hospitalisation was estimated throughout using the test-negative case-control study design where positive PCR tests from hospitalised individuals are cases and comparable negative PCR tests are controls. Multivariable logistic regression was used to assess vaccine effectiveness against hospitalisation with the test result as the outcome, vaccination status as the primary exposure variable of interest and confounder adjustment. RESULTS: There was no evidence of residual protection for boosters given as part of previous campaigns. There were 28,916 eligible tests included to estimate the effectiveness of the autumn 2023 boosters in those aged 65 years and older. VE peaked at 50.6% (95% CI: 44.2-56.3%) after 2-4 weeks, followed by waning to 13.6% (95% CI: -11.7-33.2%). Estimates were generally higher for the XBB.1.5 booster than the BA.4-5 booster, but this difference was not statistically significant. Point estimates were highest against XBB sub-lineages. Effectiveness was lower against both JN.1 and EG.5.1 variants with confidence intervals non-overlapping with the effectiveness of the XBB sub-lineages at 2-4 weeks for EG.5.1 where VE was 44.5% (95% CI: 20.2- 61.4%) and at 5-9 weeks for JN.1 where VE was 26.4% (95%CI: -3.4-47.6%). CONCLUSIONS: The recent monovalent XBB.1.5 and bivalent BA.4-5 boosters provided comparable and good protection against hospitalisation, however there was evidence of lower VE against hospitalisation of these boosters against JN.1.

Effectiveness of the Sanofi/GSK (VidPrevtyn Beta) and Pfizer-BioNTech (Comirnaty Original/Omicron BA.4-5) bivalent vaccines against hospitalisation in England.

Background: The Sanofi/GSK AS03-adjuvanted (VidPrevtyn Beta) vaccine and the Pfizer-BioNTech mRNA (Comirnaty Original/Omicron BA.4-5) bivalent vaccine were offered to adults aged 75 years and over in England from 3rd April 2023. This is the first time an adjuvanted COVID-19 vaccine has been administered as part of a UK COVID-19 vaccination programme. In clinical trials, antibody levels generated were comparable with mRNA vaccines but there are no real-world data on the effectiveness or duration of protection. Methods: We used a test-negative case-control study design to estimate the incremental vaccine effectiveness of the Sanofi/GSK and Pfizer bivalent BA.4-5 boosters against hospitalisation amongst those aged 75 years and older in England. Cases (those testing positive) and controls (those testing negative) were identified from the national COVID-19 PCR testing data undertaken in hospital settings. The study period included tests from 3rd April 2023 to 27th August 2023. Tests were linked to the COVID-19 vaccination register and to the national hospital admission database, restricting to those with an acute respiratory infection coded in the primary diagnosis field. Vaccine effectiveness was estimated using multivariable logistic regression amongst those who had last received an autumn 2022 booster given at least 3 months prior. The test result was the outcome and vaccination status the exposure. Analyses were adjusted for week of test, gender, age, clinical risk group status, care home resident status, region, index of multiple deprivation, ethnicity, influenza vaccination status and recent COVID-19 positivity. Findings: There were 14,169 eligible tests from hospitalised individuals aged 75 years and older; 3005 cases (positive tests) and 11,164 controls (negative tests). Effectiveness was highest in the period 9-13 days post vaccination for both manufacturers at about 50%; 43.7% (95% CI, 20.1-60.3%) and 56.1% (95% CI, 25.2-74.2%) for Sanofi/GSK and Pfizer BA.4-5, respectively. There was evidence of waning with a reduction to about 30% for both manufacturers after 5-9 weeks. The longest time interval post vaccination for which we were able to estimate effectiveness was 10+ weeks post vaccination, at which point vaccine effectiveness was 17.6% (95% CI, -3.6 to 34.5%) and 37.9% (95% CI, 13.2-55.5%) for the Sanofi/GSK and Pfizer BA.4-5 boosters, respectively. Interpretation: Both boosters provided good protection against hospitalisation amongst older adults. The finding that the adjuvanted vaccine targeting the distant Beta strain had similar effectiveness to the bivalent mRNA vaccine targeting more closely matched Omicron sub-lineages is notable and highlights the need for further real-world studies into the effectiveness of vaccines from different vaccine platforms and formulations in the presence of matched and unmatched strains. Funding: No external funding.

Postpandemic Sentinel Surveillance of Respiratory Diseases in the Context of the World Health Organization Mosaic Framework: Protocol for a Development and Evaluation Study Involving the English Primary Care Network 2023-2024.

BACKGROUND: Prepandemic sentinel surveillance focused on improved management of winter pressures, with influenza-like illness (ILI) being the key clinical indicator. The World Health Organization (WHO) global standards for influenza surveillance include monitoring acute respiratory infection (ARI) and ILI. The WHO's mosaic framework recommends that the surveillance strategies of countries include the virological monitoring of respiratory viruses with pandemic potential such as influenza. The Oxford-Royal College of General Practitioner Research and Surveillance Centre (RSC) in collaboration with the UK Health Security Agency (UKHSA) has provided sentinel surveillance since 1967, including virology since 1993. OBJECTIVE: We aim to describe the RSC's plans for sentinel surveillance in the 2023-2024 season and evaluate these plans against the WHO mosaic framework. METHODS: Our approach, which includes patient and public involvement, contributes to surveillance objectives across all 3 domains of the mosaic framework. We will generate an ARI phenotype to enable reporting of this indicator in addition to ILI. These data will support UKHSA's sentinel surveillance, including vaccine effectiveness and burden of disease studies. The panel of virology tests analyzed in UKHSA's reference laboratory will remain unchanged, with additional plans for point-of-care testing, pneumococcus testing, and asymptomatic screening. Our sampling framework for serological surveillance will provide greater representativeness and more samples from younger people. We will create a biomedical resource that enables linkage between clinical data held in the RSC and virology data, including sequencing data, held by the UKHSA. We describe the governance framework for the RSC. RESULTS: We are co-designing our communication about data sharing and sampling, contextualized by the mosaic framework, with national and general practice patient and public involvement groups. We present our ARI digital phenotype and the key data RSC network members are requested to include in computerized medical records. We will share data with the UKHSA to report vaccine effectiveness for COVID-19 and influenza, assess the disease burden of respiratory syncytial virus, and perform syndromic surveillance. Virological surveillance will include COVID-19, influenza, respiratory syncytial virus, and other common respiratory viruses. We plan to pilot point-of-care testing for group A streptococcus, urine tests for pneumococcus, and asymptomatic testing. We will integrate test requests and results with the laboratory-computerized medical record system. A biomedical resource will enable research linking clinical data to virology data. The legal basis for the RSC's pseudonymized data extract is The Health Service (Control of Patient Information) Regulations 2002, and all nonsurveillance uses require research ethics approval. CONCLUSIONS: The RSC extended its surveillance activities to meet more but not all of the mosaic framework's objectives. We have introduced an ARI indicator. We seek to expand our surveillance scope and could do more around transmissibility and the benefits and risks of nonvaccine therapies.

The risk of acute disseminated encephalomyelitis (ADEM) following covid-19 vaccination in England: A self-controlled case-series analysis.

Acute disseminated encephalomyelitis (ADEM) has been identified as an Adverse Event of Special Interest in the COVID-19 vaccine programme due to its long-standing temporal association with a wide range of other vaccines. Case reports of ADEM shortly following COVID-19 vaccination have now been documented. There were 217 ADEM admissions in 215 individuals in the period 8th December 2020 to 31st March 2023. An increased risk of ADEM following the first dose of ChAdOx1 vaccine was observed (relative incidence (RI) = 3.13, 95% Confidence Interval (CI) [1.56-6.25]) with a vaccine attributable risk of 0.39 per million doses. When doses 1 and 2 were combined this increased risk remained just significant (1.96 [95%CI 1.01-3.82]). No significant increased risk was observed with any other vaccine or dose. This small, elevated risk after the first dose of ChAdOx1-S vaccine demonstrates how large national electronic datasets can be used to identify very rare risks and provides reassurance that any risk of ADEM following the ChAdOx1-S COVID-19 vaccination is extremely small. Given the rarity of this risk, further studies in settings with access to data on large populations should be carried out to verify these findings.

A case of swine influenza A(H1N2)v in England, November 2023.

Under International Health Regulations from 2005, a human infection caused by a novel influenza A virus variant is considered an event that has potential for high public health impact and is immediately notifiable to the World Health Organisation. We here describe the clinical, epidemiological and virological features of a confirmed human case of swine influenza A(H1N2)v in England detected through community respiratory virus surveillance. Swabbing and contact tracing helped refine public health risk assessment, following this unusual and unexpected finding.

Effects of BNT162b2 Messenger RNA Vaccine and ChAdOx1 Adenovirus Vector Vaccine on Deaths From COVID-19 in Adults Aged ≥70 Years.

We estimated the risk of death from coronavirus disease 2019 in vaccinated compared with unvaccinated patients. The risk of death was reduced 44% after 1 dose of the Pfizer-BioNTech BNT162b2 vaccine, 55% after 1 dose of the Oxford-Astrazeneca ChAdOx1 vaccine, and 69% after 2 doses of the BNT162b2 vaccine. This is above the protection provided against infection.

Serum HCoV-spike specific antibodies do not protect against subsequent SARS-CoV-2 infection in children and adolescents.

SARS-CoV-2 infections in children are generally asymptomatic or mild and rarely progress to severe disease and hospitalization. Why this is so remains unclear. Here we explore the potential for protection due to pre-existing cross-reactive seasonal coronavirus antibodies and compare the rate of antibody decline for nucleocapsid and spike protein in serum and oral fluid against SARS-CoV-2 within the pediatric population. No differences in seasonal coronaviruses antibody concentrations were found at baseline between cases and controls, suggesting no protective effect from pre-existing immunity against seasonal coronaviruses. Antibodies against seasonal betacoronaviruses were boosted in response to SARS-CoV-2 infection. In serum, anti-nucleocapsid antibodies fell below the threshold of positivity more quickly than anti-spike protein antibodies. These findings add to our understanding of protection against infection with SARS-CoV-2 within the pediatric population, which is important when considering pediatric SARS-CoV-2 immunization policies.

Effectiveness of BNT162b2 and ChAdOx1 against SARS-CoV-2 household transmission: a prospective cohort study in England.

Background: The ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated the effectiveness of Pfizer-BioNTech mRNA vaccine (BNT162b2) and Oxford AstraZeneca adenovirus vector vaccine (ChAdOx1) vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. Methods: Households were recruited based on adult purported index cases testing positive after reverse transcription-quantitative (RT-q)PCR testing of oral-nasal swabs. Purported index cases and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment and a subset of the PCR-positive swabs underwent genomic sequencing conducted on a subset. We used Bayesian logistic regression to infer vaccine effectiveness against acquisition and transmission, adjusted for age, vaccination history and variant. Results: Between 2 February 2021 and 10 September 2021, 213 index cases and 312 contacts were followed up. After excluding households lacking genomic proximity (N=2) or with unlikely serial intervals (N=16), 195 households with 278 contacts remained, of whom 113 (41%) became PCR positive. Delta lineages had 1.53 times the risk (95% Credible Interval: 1.04 - 2.20) of transmission than Alpha; contacts older than 18 years old were 1.48 (1.20 - 1.91) and 1.02 (0.93 - 1.16) times more likely to acquire an Alpha or Delta infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 36% (-1%, 66%) and 49% (18%, 73%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 69% (9%, 95%) vs. 18% (-11%, 59%), respectively, for BNT162b2 and 24% (-41%, 72%) vs. 9% (-15%, 42%), respectively, for ChAdOx1. Conclusions: BNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting, although their protection against infection within this setting is low.

Temporal changes to adult case fatality risk of COVID-19 after vaccination in England between May 2020 and February 2022: a national surveillance study.

OBJECTIVES: Risk of death after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has fallen during the pandemic, largely due to immunity from vaccination. In England, the timing and extent of this reduction varied due to staggered eligibility during the primary vaccination campaign, based on age and clinical risk group. Duration of protection is less well understood. Our objective was to estimate the case fatality risk (CFR) by vaccination status and time since last dose during a period of widespread community testing, to better understand the impact of coronavirus disease 2019 (COVID-19) vaccination and duration of protection. DESIGN: SARS-CoV-2 cases diagnosed between May 2020 and February 2022 were linked to vaccine records from the National Immunisation Management System. CFR was calculated as the proportion of cases that died of COVID-19 per the death certificate, aggregated by week of specimen and stratified by 10-year age band and vaccination status. SETTING: England, UK. PARTICIPANTS: A total of 10,616,148 SARS-CoV-2 cases, aged ≥18 years, recorded by England's laboratory reporting system. MAIN OUTCOME MEASURES: Case fatality risk of COVID-19, stratified by age band and vaccination status. RESULTS: Overall, a reduction in CFR was observed for all age bands, with a clear temporal link to when the age group became eligible for primary vaccination and then the first booster. CFR increased with age (0.3% 50-59 years; 1.2% 60-69; 4.7% 70-79; 16.3% 80+) and was highest in the unvaccinated - albeit a reduction was observed over time. The highest CFR was seen in the unvaccinated 80+ group prior to vaccination rollout (30.6%). CFR was consistently lowest in vaccinated populations within 6 months of last dose, yet increased after over 6 months elapsed since last dose, across all age bands. CONCLUSIONS: COVID-19 CFR reduced after vaccination, with the lowest CFR seen across all age bands when vaccinated up to 6 months prior to specimen date. This provides some evidence for continued booster doses in older age groups.

High attack rate in a large care home outbreak of SARS-CoV-2 BA.2.86, East of England, August 2023.

We investigated an outbreak of SARS-CoV-2 variant BA.2.86 in an East of England care home. We identified 45 infections (33 residents, 12 staff), among 38 residents and 66 staff. Twenty-nine of 43 PCR swabs were sequenced, all of which were variant BA.2.86. The attack rate among residents was 87%, 19 were symptomatic, and one was hospitalised. Twenty-four days after the outbreak started, no cases were still unwell. Among the 33 resident cases, 29 had been vaccinated 4 months earlier.

COVID-19 vaccine effectiveness against hospitalisation and death of people in clinical risk groups during the Delta variant period: English primary care network cohort study.

BACKGROUND: COVID-19 vaccines have been shown to be highly effective against hospitalisation and death following COVID-19 infection. COVID-19 vaccine effectiveness estimates against severe endpoints among individuals with clinical conditions that place them at increased risk of critical disease are limited. METHODS: We used English primary care medical record data from the Oxford-Royal College of General Practitioners Research and Surveillance Centre sentinel network (N > 18 million). Data were linked to the National Immunisation Management Service database, Second Generation Surveillance System for virology test data, Hospital Episode Statistics, and death registry data. We estimated adjusted vaccine effectiveness (aVE) against COVID-19 infection followed by hospitalisation and death among individuals in specific clinical risk groups using a cohort design during the delta-dominant period. We also report mortality statistics and results from our antibody surveillance in this population. FINDINGS: aVE against severe endpoints was high, 14-69d following a third dose aVE was 96.4% (95.1%-97.4%) and 97.9% (97.2%-98.4%) for clinically vulnerable people given a Vaxzevria and Comirnaty primary course respectively. Lower aVE was observed in the immunosuppressed group: 88.6% (79.1%-93.8%) and 91.9% (85.9%-95.4%) for Vaxzevria and Comirnaty respectively. Antibody levels were significantly lower among the immunosuppressed group than those not in this risk group across all vaccination types and doses. The standardised case fatality rate within 28 days of a positive test was 3.9/1000 in people not in risk groups, compared to 12.8/1000 in clinical risk groups. Waning aVE with time since 2nd dose was also demonstrated, for example, Comirnaty aVE against hospitalisation reduced from 96.0% (95.1-96.7%) 14-69days post-dose 2-82.9% (81.4-84.2%) 182days+ post-dose 2. INTERPRETATION: In all clinical risk groups high levels of vaccine effectiveness against severe endpoints were seen. Reduced vaccine effectiveness was noted among the immunosuppressed group.

Duration of protection of ancestral-strain monovalent vaccines and effectiveness of bivalent BA.1 boosters against COVID-19 hospitalisation in England: a test-negative case-control study.

BACKGROUND: Bivalent BA.1 booster vaccines were offered to adults aged 50 years or older and clinically vulnerable people as part of the 2022 autumn COVID-19 booster vaccination programme in England. Previously, all adults in England had been offered a primary course consisting of two doses of either ChAdOx1-S or monovalent mRNA vaccine and an mRNA monovalent booster vaccine. We aimed to estimate the long-term duration of protection provided by monovalent COVID-19 vaccines, and the incremental vaccine effectiveness of bivalent BA.1 boosters. METHODS: In this test-negative case-control study, cases of COVID-19 and controls aged 18 years or older were identified from national data for PCR tests done in hospital settings in England. Our analysis was restricted to people with acute respiratory infections coded in the primary diagnosis field. Data for vaccination status were extracted from the English national vaccine register and linked to COVID-19 testing data. Between June 13 and Dec 25, 2022, we estimated the vaccine effectiveness against hospitalisation of two or three or more doses of monovalent COVID-19 vaccines compared with being unvaccinated, stratified by age (18-64 years vs ≥65 years). Between Sept 5, 2022, and Feb 5, 2023, we estimated the incremental vaccine effectiveness (ie, in addition to the protection from earlier vaccines) of receiving a bivalent BA.1 booster vaccine in addition to at least two doses of a monovalent vaccine (when the last dose was at least 6 months ago) among people aged 50 years or older. Analyses were adjusted for week of test, gender, age, COVID-19 risk group, residing in a care home, being a health or social care worker, Index of Multiple Deprivation quintile, ethnicity, and recent COVID-19 positivity. FINDINGS: Our analysis of monovalent COVID-19 vaccines included 19 841 cases and 43 410 controls. Absolute vaccine effectiveness against hospitalisation among people who had received at least three doses plateaued from 6 months after the last dose at around 50% in those aged 65 years or older and at around 30% in those aged 18-64 years. Our analyses of the effectiveness of bivalent BA.1 boosters included data for 9954 cases and 39 108 controls aged 50 years or older. Incremental vaccine effectiveness peaked at 53·0% (95% CI 47·9-57·5) 2-4 weeks after administration, before waning to 35·9% (31·4-40·1) after 10 or more weeks. INTERPRETATION: Our study provides evidence that monovalent COVID-19 vaccines offer moderate long-term protection against hospitalisation in people aged 65 years or older and that the bivalent BA.1 booster vaccines were effective in preventing hospitalisation among people aged 50 years or older at a time when omicron lineages were circulating in England. FUNDING: None.

Early evaluation of the safety, reactogenicity, and immune response after a single dose of modified vaccinia Ankara-Bavaria Nordic vaccine against mpox in children: a national outbreak response.

BACKGROUND: In response to a national mpox (formerly known as monkeypox) outbreak in England, children exposed to a confirmed mpox case were offered modified vaccinia Ankara-Bavaria Nordic (MVA-BN), a third-generation smallpox vaccine, for post-exposure prophylaxis. We aimed to assess the safety and reactogenicity and humoral and cellular immune response, following the first reported use of MVA-BN in children. METHODS: This is an assessment of children receiving MVA-BN for post-exposure prophylaxis in response to a national mpox outbreak in England. All children receiving MVA-BN were asked to complete a post-vaccination questionnaire online and provide a blood sample 1 month and 3 months after vaccination. Outcome measures for the questionnaire included reactogenicity and adverse events after vaccination. Blood samples were tested for humoural, cellular, and cytokine responses and compared with unvaccinated paediatric controls who had never been exposed to mpox. FINDINGS: Between June 1 and Nov 30, 2022, 87 children had one MVA-BN dose and none developed any serious adverse events or developed mpox disease after vaccination. Post-vaccination reactogenicity questionnaires were completed by 45 (52%) of 87 children. Their median age was 5 years (IQR 5-9), 25 (56%) of 45 were male, and 22 (49%) of 45 were White. 16 (36%) reported no symptoms, 18 (40%) reported local reaction only, and 11 (24%) reported systemic symptoms with or without local reactions. Seven (8%) of 87 children provided a first blood sample a median of 6 weeks (IQR 6·0-6·5) after vaccination and five (6%) provided a second blood sample at a median of 15 weeks (14-15). All children had poxvirus IgG antibodies with titres well above the assay cutoff of OD450nm 0·1926 with mean absorbances of 1·380 at six weeks and 0·9826 at 15 weeks post-vaccination. Assessment of reactivity to 27 recombinant vaccina virus and monkeypox virus proteins showed humoral antigen recognition, primarily to monkeypox virus antigens B6, B2, and vaccina virus antigen B5, with waning of humoral responses observed between the two timepoints. All children had a robust T-cell response to whole modified vaccinia Ankara virus and a select pool of conserved pan-Poxviridae peptides. A balanced CD4+ and CD8+ T-cell response was evident at 6 weeks, which was retained at 15 weeks after vaccination. INTERPRETATION: A single dose of MVA-BN for post-exposure prophylaxis was well-tolerated in children and induced robust antibody and cellular immune responses up to 15 weeks after vaccination. Larger studies are needed to fully assess the safety, immunogenicity, and effectiveness of MVA-BN in children. Our findings, however, support its on-going use to prevent mpox in children as part of an emergency public health response. FUNDING: UK Health Security Agency.

Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant (B.1.1.529) rapidly replaced Delta (B.1.617.2) to become dominant in England. Our study assessed differences in transmission between Omicron and Delta using two independent data sources and methods. Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for named contacts were calculated in household and non-household settings using contact tracing data, while household clustering was identified using national surveillance data. Logistic regression models were applied to control for factors associated with transmission for both methods. For contact tracing data, higher secondary attack rates for Omicron vs. Delta were identified in households (15.0% vs. 10.8%) and non-households (8.2% vs. 3.7%). For both variants, in household settings, onward transmission was reduced from cases and named contacts who had three doses of vaccine compared to two, but this effect was less pronounced for Omicron (adjusted risk ratio, aRR 0.78 and 0.88) than Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed only in contacts who had three doses vs. two doses for both Delta (aRR 0.51) and Omicron (aRR 0.76). For national surveillance data, the risk of household clustering, was increased 3.5-fold for Omicron compared to Delta (aRR 3.54 (3.29-3.81)). Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Epidemiology of hospitalisations due to chickenpox and quality of life lost in community and hospital settings: protocol for a prospective cohort study across two countries.

INTRODUCTION: While still a ubiquitous disease of childhood, chickenpox has been effectively controlled in many countries through the use of vaccination. Previous health economic assessment of the use of these vaccines in the UK were based on limited quality of life data and only routinely collected epidemiological outcomes. METHODS AND ANALYSIS: This two armed study will carry prospective surveillance of hospital admissions and recruit from community settings to measure the acute quality of life loss caused by paediatric chickenpox both in the UK and in Portugal. The quality of life effects on children and their primary and secondary caregivers will be assessed using the EuroQol EQ-5D with the Child Health Utility instrument (CHU-9) in addition for children. Results will be used to derive quality-adjusted life year loss estimates for cases of simple varicella and the secondary complications. ETHICS AND DISSEMINATION: We have received National Health Service ethical approval (REC ref: 18/ES/0040) for the inpatient arm, university ethical approval (University of Bristol ref: 60721) for the community arm and 10 sites currently are recruiting in the UK and 14 in Portugal. Informed consent is obtained from the parent(s). Results will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: ISRCTN15017985.

Effects of Second Dose of SARS-CoV-2 Vaccination on Household Transmission, England.

A single SARS-CoV-2 vaccine dose reduces onward transmission from case-patients. We assessed the potential effects of receiving 2 doses on household transmission for case-patients in England and their household contacts. We used stratified Cox regression models to calculate hazard ratios (HRs) for contacts becoming secondary case-patients, comparing contacts of 2-dose vaccinated and unvaccinated index case-patients. We controlled for age, sex, and vaccination status of case-patients and contacts, as well as region, household composition, and relative socioeconomic condition based on household location. During the Alpha-dominant period, HRs were 0.19 (0.13-0.28) for contacts of 2-dose BNT162b2-vaccinated case-patients and 0.54 (0.41-0.69) for contacts of 2-dose Ch4dOx1-vaccinated case-patients; during the Delta-dominant period, HRs were higher, 0.74 (0.72-0.76) for BNT162b2 and 1.06 (1.04-1.08) for Ch4dOx1. Reduction of onward transmission was lower for index case-patients who tested positive ≥2 months after the second dose of either vaccine.

A Re-emergence of Subacute Sclerosing Panencephalitis in the United Kingdom.

New pediatric and adult subacute sclerosing panencephalitis cases between 1996 and 2020 were reported based on an established UK registry with no evidence of under-ascertainment using a separate pediatric surveillance system. After 15 years with no pediatric UK-acquired cases, 3 cases arose from 2017 after increased measles. Modeling suggested this was in line with measles notifications, underreporting of laboratory-confirmed measles or increased subacute sclerosing panencephalitis risk.

Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021-March, 2022: a national, observational, test-negative, case-control study.

BACKGROUND: 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. METHODS: 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). FINDINGS: 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. INTERPRETATION: 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. FUNDING: None.

Monitoring the COVID-19 immunisation programme through a national immunisation Management system - England's experience.

BACKGROUND: In England routine vaccinations are recorded in either the patients General Practice record or in series of sub-national vaccine registers that are not interoperable. During the COVID-19 pandemic it was established that COVID vaccines would need to be delivered in multiple settings where current vaccine registers do not exist. We describe how a national vaccine register was created to collect data on COVID-19 vaccines. METHODS: The National Immunisation Management System (NIMS) was developed by a range of health and digital government agencies. Vaccinations delivered are entered on an application which is verified by individual National Health Service number in a centralised system. UKHSA receive a feed of this data to use for monitoring vaccine coverage, effectiveness, and safety. To validate the vaccination data, we compared vaccine records to self-reported vaccination dose, manufacturer, and vaccination date from the enhanced surveillance system from 11 February 2021 to 24 August 2021. RESULTS: With the Implementation of NIMS, we have been able to successfully record COVID-19 vaccinations delivered in multiple settings. Of 1,129 individuals, 97.8% were recorded in NIMS as unvaccinated compared to those who self-reported as unvaccinated. One hundred percent and 99.3% of individuals recorded in NIMS as having at least one dose and two doses of the COVID-19 vaccine were also self-reported as having at least one and two doses, respectively. Of the 100% reporting at least one dose, 98.3% self-reported the same vaccination date as NIMS. A total of 98.8% and 99.3% had the same manufacturer information for their first dose and second dose as that which was self-reported, respectively. DISCUSSION: Daily access to individual-level vaccine data from NIMS has allowed UKHSA to estimate vaccine coverage and provide some of the world's first vaccine effectiveness estimates rapidly and accurately.