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.

Influenza vaccination during the 2021/22 season: A data-linkage test-negative case-control study of effectiveness against influenza requiring emergency care in England and serological analysis of primary care patients.

We present England 2021/22 end-of-season adjusted vaccine effectiveness (aVE) against laboratory confirmed influenza related emergency care use in children aged 1-17 and in adults aged 50+, and serological findings in vaccinated vs unvaccinated adults by hemagglutination inhibition assay. Influenza vaccination has been routinely offered to all children aged 2-10 years and adults aged 65 years + in England. In 2021/22, the offer was extended to children to age 15 years, and adults aged 50-64 years. Influenza activity rose during the latter half of the 2021/22 season, while remaining comparatively low due to COVID-19 pandemic control measures. Influenza A(H3N2) strains predominated. A test negative design was used to estimate aVE by vaccine type. Cases and controls were identified within a sentinel laboratory surveillance system. Vaccine histories were obtained from the National Immunisation Management Service (NIMS), an influenza and COVID-19 vaccine registry. These were linked to emergency department presentations (excluding accidents) with respiratory swabbing ≤ 14 days before or ≤ 7 days after presentation. Amongst adults, 423 positive and 32,917 negative samples were eligible for inclusion, and 145 positive and 6,438 negative samples among children. Those admitted to hospital were further identified. In serology against the circulating A(H3N2) A/Bangladesh/4005/2020-like strain, 61 % of current season adult vaccinees had titres ≥ 1:40 compared to 17 % of those unvaccinated in 2020/21 or 2021/22 (p < 0.001). We found good protection from influenza vaccination against influenza requiring emergency care in children (72.7 % [95 % CI 52.7, 84.3 %]) and modest effectiveness in adults (26.1 % [95 % CI 4.5, 42.8 %]). Adult VE was higher for A(H1N1) (81 % [95 % CI 50, 93 %]) than A(H3N2) (33 % [95 % CI 6, 53 %]). Consistent protection was observable across preschool, primary and secondary school aged children. Imperfect test specificity combined with very low prevalence may have biased estimates towards null. With limited influenza circulation, the study could not determine differences by vaccine types.

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.

Erratum to "Risk of cardiac arrhythmia and cardiac arrest after primary and booster COVID-19 vaccination in England: A self-controlled case series analysis" [Vaccine: X 15 (2023) 100418].

[This corrects the article DOI: 10.1016/j.jvacx.2023.100418.].

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.

Risk of cardiac arrhythmia and cardiac arrest after primary and booster COVID-19 vaccination in England: A self-controlled case series analysis.

Background: Various cardiac arrhythmias have been reported after COVID-19 infection and vaccination. We assessed the risk after primary immunisation with the ChAdOx1 adenovirus vectored vaccine, and primary and booster immunisation with an mRNA vaccine in 40 million vaccinated adults with 121 million doses (33.9% ChAdOx1 and 66.1% mRNA) in England. Methods: Hospital admissions for a cardiac arrhythmia and emergency care attendance for a cardiac arrest in individuals aged 18 years and older on the 31st March 2021 were linked to the national COVID-19 immunisation register. The incidence of events 1-14 and 15-28 days after vaccination relative to a post-vaccination control period was estimated using the self-controlled case series method modified for fatal events. Outcomes were stratified by arrhythmia type, vaccine type, age group and dose number (up to five). Elevated relative incidence (RI) estimates with p < 0.001 were considered strong evidence of an association. Findings: There was an increased risk of admission for arrhythmia events that were largely palpitations without myocarditis within 14 days of a second priming dose of an mRNA vaccine in 18-49 year olds with an RI of 1.66 (95 % confidence interval 1.47,1.86) for BNT162b2 and 3.75 (2.52,5.57) for mRNA-1273 (p < 0.001) and also after a first booster dose, 1.34 (1.17,1.53) and 1.75 (1.43,2.15) respectively (p < 0.001). No other cardiac arrhythmia, including cardiac arrest, showed an elevated incidence within 28 days of vaccination for any dose, age group or vaccine type. In contrast the risk of a cardiac arrhythmia of all types, including a cardiac arrest, was consistently elevated in those testing positive for SARS-CoV-2 infection. Interpretation: Our study provides reassuring evidence of the safety of the ChAdOx1 and mRNA COVID-19 vaccines with respect to serious cardiac arrhythmias and of the favourable risk benefit of mRNA booster vaccination.

Vaccine effectiveness against hospitalisation estimated using a test-negative case-control study design, and comparative odds of hospital admission and severe outcomes with COVID-19 sub-lineages BQ.1, CH.1.1. and XBB.1.5 in England.

Background: Since the first emergence of Omicron BA.1 in England in November 2021, numerous sub-lineages have evolved. In September 2022, BA.5 dominated. The prevalence of BQ.1 increased from October, while the prevalence of CH.1.1 and XBB.1.5 increased from December 2022 and January 2023, respectively. Little is known about the effectiveness of the vaccines against hospitalisation with these sub-lineages, nor the relative severity, so we here used national-level electronic health records from England to estimate vaccine effectiveness and variant severity. Methods: The study period for tests contributing to all analyses was from 5th December 2022 to 2nd April 2023, when the variants of interest were co-circulating. A test-negative case-control study was used to estimate the incremental effectiveness of the bivalent BA.1 booster vaccines against hospitalisation, relative to those with waned immunity where the last dose was at least 6 months prior. The odds of hospital admission for those testing PCR positive on the day of an attendance to accident and emergency departments and the odds of intensive care unit admission or death amongst COVID-19 admissions were compared between variants. Additionally, a Cox proportional hazards survival regression was used to investigate length of stay amongst hospitalised cases by variant. Findings: Our vaccine effectiveness study included 191,229 eligible tests with 1647 BQ.1 cases, 877 CH.1.1 cases, 1357 XBB.1.5 cases and 187,348 test negative controls. There was no difference in incremental vaccine effectiveness against hospitalisation with BQ.1, CH.1.1 or XBB.1.5, nor was there a difference in the severity of these variants. Effectiveness against hospitalisation was 48.0% (95% C.I.; 38.5-56.0%), 29.7% (95% C.I.; 7.5-46.6%) and 52.7% (95% C.I.; 24.6-70.4%) against BQ.1, CH.1.1 and XBB.1.5, respectively, at 5-9 weeks post booster vaccination. Compared to BQ.1, the odds of hospital admission were 0.87 (95% C.I.; 0.77-0.99) and 0.88 (95% C.I.; 0.75-1.02) for CH.1.1 and XBB.1.5 cases attending accident and emergency departments, respectively. There was no significant difference in the odds of admission to intensive care units or death for those with CH.1.1 (OR 0.96, 95% C.I.; 0.71-1.30) or XBB.1.5 (OR 0.67, 95% C.I.; 0.44-1.02) compared to BQ.1. There was also no significant difference in the length of hospital stay by variant. Interpretation: Together, these results provide reassuring evidence that the bivalent BA.1 booster vaccines provide similar protection against hospitalisation with BQ.1, CH.1.1 and XBB.1.5, and that the emergent CH.1.1 and XBB.1.5 sub-lineages do not cause more severe disease than BQ.1. Funding: None.

Increased reports of severe myocarditis associated with enterovirus infection in neonates, United Kingdom, 27 June 2022 to 26 April 2023.

Enteroviruses are a common cause of seasonal childhood infections. The vast majority of enterovirus infections are mild and self-limiting, although neonates can sometimes develop severe disease. Myocarditis is a rare complication of enterovirus infection. Between June 2022 and April 2023, twenty cases of severe neonatal enteroviral myocarditis caused by coxsackie B viruses were reported in the United Kingdom. Sixteen required critical care support and two died. Enterovirus PCR on whole blood was the most sensitive diagnostic test. We describe the initial public health investigation into this cluster and aim to raise awareness among paediatricians, laboratories and public health specialists.

Bias assessment of a test-negative design study of COVID-19 vaccine effectiveness used in national policymaking.

National test-negative-case-control (TNCC) studies are used to monitor COVID-19 vaccine effectiveness in the UK. A questionnaire was sent to participants from the first published TNCC COVID-19 vaccine effectiveness study conducted by the UK Health Security Agency, to assess for potential biases and changes in behaviour related to vaccination. The original study included symptomatic adults aged ≥70 years testing for COVID-19 between 08/12/2020 and 21/02/2021. A questionnaire was sent to cases and controls tested from 1-21 February 2021. In this study, 8648 individuals responded to the questionnaire (36.5% response). Using information from the questionnaire to produce a combined estimate that accounted for all potential biases decreased the original vaccine effectiveness estimate after two doses of BNT162b2 from 88% (95% CI: 79-94%) to 85% (95% CI: 68-94%). Self-reported behaviour demonstrated minimal evidence of riskier behaviour after vaccination. These findings offer reassurance to policy makers and clinicians making decisions based on COVID-19 vaccine effectiveness TNCC studies.

Re-evaluation of the risk of venous thromboembolism after COVID-19 vaccination using haematological criteria.

An elevated risk of venous thromboembolism (VTE) following a first dose of the ChAdOx1 adenovirus-vectored vaccine was found in a national epidemiological study in England using routine discharge diagnosis codes. Separately, the syndrome of vaccine-induced immune thrombotic thrombocytopenia (VITT) was identified using haematological criteria based on presence of thrombocytopenia, significantly elevated D-dimers and development of anti-PF4 antibodies. To re-evaluate risk estimates using haematological criteria, we obtained the haematology results for hospital admitted patients aged 18-64 years in 43 National Health Service trusts in England who were included in the national epidemiological study. Diagnoses were confirmed and haematological parameters obtained from local records without knowledge of vaccination status. The haematological parameters in patients admitted for a confirmed VTE following ChAdOx1 or BNT162b2 mRNA vaccination were then compared with those in a randomly selected 40% sample of unvaccinated patients with VTE. Overall, 12 (14%) of the 84 vaccinated cases had a diagnosis compatible with VITT, 11 after a first dose of ChAdOx1 and one after a first dose of BNT162b2. Thrombocytopenia (platelet count <150 × 109/L) occurred in 17 vaccinated (20%) and 4 (4%) of 108 unvaccinated patients, with all 6 cases of severe thrombocytopenia (<50 × 109/L) occurring within 42 days of a first dose of ChAdOx1. The attributable risk estimates for a cerebral venous thrombosis (CVT) or other VTE with thrombocytopenia after a first dose of ChAdOx1 vaccine were 2.82 and 9.62 per million doses respectively. However, elevated risks were also found after a first dose of ChAdOx1 for VTE without thrombocytopenia with relative incidences for CVT and other VTE of 2.67 (1.77-3.77) and 1.93 (1.57-2.35) respectively. While we identified a distinct population with features of VITT within 42 days of receiving ChAdOx1 vaccination, confirming current diagnostic criteria, we also found evidence of an increased risk of a VTE without thrombocytopenia after ChAdOx1 vaccine.

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.

Risk of myocarditis and pericarditis after a COVID-19 mRNA vaccine booster and after COVID-19 in those with and without prior SARS-CoV-2 infection: A self-controlled case series analysis in England.

BACKGROUND: An increased risk of myocarditis or pericarditis after priming with mRNA Coronavirus Disease 2019 (COVID-19) vaccines has been shown but information on the risk post-booster is limited. With the now high prevalence of prior Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, we assessed the effect of prior infection on the vaccine risk and the risk from COVID-19 reinfection. METHODS AND FINDINGS: We conducted a self-controlled case series analysis of hospital admissions for myocarditis or pericarditis in England between 22 February 2021 and 6 February 2022 in the 50 million individuals eligible to receive the adenovirus-vectored vaccine (ChAdOx1-S) for priming or an mRNA vaccine (BNT162b2 or mRNA-1273) for priming or boosting. Myocarditis and pericarditis admissions were extracted from the Secondary Uses Service (SUS) database in England and vaccination histories from the National Immunisation Management System (NIMS); prior infections were obtained from the UK Health Security Agency's Second-Generation Surveillance Systems. The relative incidence (RI) of admission within 0 to 6 and 7 to 14 days of vaccination compared with periods outside these risk windows stratified by age, dose, and prior SARS-CoV-2 infection for individuals aged 12 to 101 years was estimated. The RI within 27 days of an infection was assessed in the same model. There were 2,284 admissions for myocarditis and 1,651 for pericarditis in the study period. Elevated RIs were only observed in 16- to 39-year-olds 0 to 6 days postvaccination, mainly in males for myocarditis. Both mRNA vaccines showed elevated RIs after first, second, and third doses with the highest RIs after a second dose 5.34 (95% confidence interval (CI) [3.81, 7.48]; p < 0.001) for BNT162b2 and 56.48 (95% CI [33.95, 93.97]; p < 0.001) for mRNA-1273 compared with 4.38 (95% CI [2.59, 7.38]; p < 0.001) and 7.88 (95% CI [4.02, 15.44]; p < 0.001), respectively, after a third dose. For ChAdOx1-S, an elevated RI was only observed after a first dose, RI 5.23 (95% CI [2.48, 11.01]; p < 0.001). An elevated risk of admission for pericarditis was only observed 0 to 6 days after a second dose of mRNA-1273 vaccine in 16 to 39 year olds, RI 4.84 (95% CI [1.62, 14.01]; p = 0.004). RIs were lower in those with a prior SARS-CoV-2 infection than in those without, 2.47 (95% CI [1.32,4.63]; p = 0.005) versus 4.45 (95% [3.12, 6.34]; p = 0.001) after a second BNT162b2 dose, and 19.07 (95% CI [8.62, 42.19]; p < 0.001) versus 37.2 (95% CI [22.18, 62.38]; p < 0.001) for mRNA-1273 (myocarditis and pericarditis outcomes combined). RIs 1 to 27 days postinfection were elevated in all ages and were marginally lower for breakthrough infections, 2.33 (95% CI [1.96, 2.76]; p < 0.001) compared with 3.32 (95% CI [2.54, 4.33]; p < 0.001) in vaccine-naïve individuals respectively. CONCLUSIONS: We observed an increased risk of myocarditis within the first week after priming and booster doses of mRNA vaccines, predominantly in males under 40 years with the highest risks after a second dose. The risk difference between the second and the third doses was particularly marked for the mRNA-1273 vaccine that contains half the amount of mRNA when used for boosting than priming. The lower risk in those with prior SARS-CoV-2 infection, and lack of an enhanced effect post-booster, does not suggest a spike-directed immune mechanism. Research to understand the mechanism of vaccine-associated myocarditis and to document the risk with bivalent mRNA vaccines is warranted.

BA.1 Bivalent COVID-19 Vaccine Use and Stroke in England.

This study investigates the association between bivalent COVID-19 vaccines and ischemic stroke, as well as the effect of simultaneous influenza vaccination on the association.

Optimization of Timing of Maternal Pertussis Immunization From 6 Years of Postimplementation Surveillance Data in England.

BACKGROUND: England's third-trimester maternal pertussis vaccination, introduced in October 2012, was extended to the second trimester in 2016. Maternal vaccination provides high protection against infant disease, but routine second-trimester vaccination has not previously been assessed. METHODS: National laboratory-confirmed pertussis case surveillance determined vaccination history, maternal vaccination history and hospitalization. Pertussis hospital admissions between 2012 and 2019 were extracted from the Hospital Episode Statistics data set. Vaccine effectiveness (VE) was calculated for pertussis case patients born between October 2012 and September 2018 using the screening method and matching with a nationally representative data set. RESULTS: Higher coverage was observed after earlier maternal vaccination with approximately 40% of pregnant women vaccinated ≥13 weeks before delivery. Cases and hospitalizations stabilized at low levels in younger infants but remained elevated in older infants, children, and adults. No deaths occurred in infants with vaccinated mothers after 2016. Of 1162 laboratory-confirmed pertussis cases in the study, 599 (52%) were in infants aged <93 days: 463 (77%) with unvaccinated and 136 (23%) with vaccinated mothers. The VE was equivalent in infants with mothers vaccinated at different gestational periods except in those with mothers vaccinated between 7 days before and 41 days after delivery. Children whose mothers were unvaccinated but with vaccination in a previous pregnancy had a VE against disease of 44% (95% confidence interval, 19%-75%). There was no increased disease risk after primary vaccination in children with mothers vaccinated at least 7 days before delivery. CONCLUSIONS: National policy recommending vaccination in the second trimester increased earlier maternal vaccine uptake with sustained high VE and impact against early infant disease.

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.

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.

Effectiveness of ChAdOx1-S COVID-19 booster vaccination against the Omicron and Delta variants in England.

Despite the availability of the ChAdOx1-S booster vaccine, little is known about the real-world effectiveness although clinical trials have demonstrated enhanced immunity following a ChAdOx1-S booster. In England 43,171 individuals received a ChAdOx1-S booster whilst 13,038,908 individuals received BNT162b2 in the same period. ChAdOx1-S booster recipients were more likely to be female (adjusted odds ratio (OR) 1.67 (1.64-1.71)), in a clinical risk group (adjusted OR 1.58 (1.54-1.63)), in the clinically extremely vulnerable group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)). The effectiveness of the ChAdOx1-S and BNT162b2 boosters is estimated here using a test-negative case-control study. Protection against symptomatic disease with the Omicron variant peaks at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) for the ChAdOx1-S and BNT162b2 boosters in older adults. Protection against hospitalisation peaks at 82.3% (64.2 to 91.3%) and 90.9% (88.7 to 92.7%). For Delta, effectiveness against hospitalisation is 80.9% (15.6% to 95.7%) and 93.9% (92.8% to 94.9%) after ChAdOx1-S and BNT162b2 booster vaccination. This study supports the consideration of ChAdOx1-S booster vaccination for protection against severe COVID-19 in settings yet to offer boosters and suggests that individuals who received a ChAdOx1-S booster do not require re-vaccination ahead of others.

Effectiveness of COVID-19 vaccines against Omicron and Delta hospitalisation, a test negative case-control study.

The Omicron variant has been associated with reduced vaccine effectiveness (VE) against mild disease with rapid waning. Meanwhile Omicron has also been associated with milder disease. Protection against severe disease has been substantially higher than protection against infection with previous variants. We used a test-negative case-control design to estimate VE against hospitalisation with the Omicron and Delta variants using PCR testing linked to hospital records. We investigated the impact of increasing the specificity and severity of hospitalisation definitions on VE. Among 18-64-year-olds using cases admitted via emergency care, VE after a 3rd dose peaked at 82.4% and dropped to 53.6% by 15+ weeks after the 3rd dose; using all admissions for > = 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% to 67.4%; further restricting to those on oxygen/ventilated/intensive care VE ranged from 97.1% to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% to 76.9%; 91.3% to 85.3% and 95.8% to 86.8%. Here we show that with milder Omicron disease contamination of hospitalisations with incidental cases is likely to reduce VE estimates. VE estimates increase, and waning is reduced, when specific hospitalisation definitions are used.

Guillain-Barré syndrome following SARS-CoV-2 vaccination in the UK: a prospective surveillance study.

Objective: To investigate features of Guillain-Barré syndrome (GBS) following SARS-CoV-2 vaccines and evaluate for a causal link between the two. Methods: We captured cases of GBS after SARS-CoV-2 vaccination through a national, open-access, online surveillance system. For each case, the certainty of GBS was graded using the Brighton criteria, and the relationship to the vaccine was examined using modified WHO Causality Assessment criteria. We compared age distribution of cases with that of prepandemic GBS cases and clinical features with the International GBS Outcome Study (IGOS). Results: Between 1 January and 30 June 2021, we received 67 reports of GBS following the ChAdOx1 vaccine (65 first doses) and three reports following the BNT162b2 vaccine (all first doses). The causal association with the vaccine was classified as probable for 56 (80%, all ChAdOx1), possible for 12 (17%, 10 ChAdOx1) and unlikely for two (3%, 1 ChAdOx1). A greater proportion of cases occurred in the 50-59 age group in comparison with prepandemic GBS. Most common clinical variants were sensorimotor GBS (n=55; 79%) and facial diplegia with paraesthesias (n=10; 14%). 10% (n=7/69) of patients reported an antecedent infection, compared with 77% (n=502/652) of the IGOS cohort (p<0.00001). Facial weakness (63% (n=44/70) vs 36% (n=220/620); p<0.00001) and sensory dysfunction (93% (n=63/68) vs 69% (n=408/588); p=0.00005) were more common but disease severity and outcomes were similar to the IGOS study. Interpretation: Most reports of GBS followed the first dose of ChAdOx1 vaccine. While our study cannot confirm or refute causation, this observation, together with the absence of alternative aetiologies, different than expected age distribution and the presence of unusual clinical features support a causal link. Clinicians and surveillance bodies should remain vigilant to the possibility of this very rare adverse event and its atypical variants.