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The Omicron sub-lineages BA.4 and BA.5 were first detected in England in April 2022. A case surge followed despite England having recently experienced waves with BA.1 and BA.2. This study used a whole population test-negative case-control study design to estimate the effectiveness of the vaccines currently in use as part of the UK COVID-19 vaccination programme against hospitalisation following infection with BA.4 and BA.5 as compared to BA.2 during a period of co-circulation. Incremental VE was estimated in those vaccinated with either a third or fourth dose as compared to individuals with waned immunity who had received their second dose at least 25 weeks prior. Vaccination status was included as an independent variable and effectiveness was defined as 1-odds of vaccination in cases/odds of vaccination in controls. During the study period, there were 32,845 eligible tests from hospitalised individuals. Of these, 25,862 were negative (controls), 3,432 were BA.2, 273 were BA.4, 947 were BA.5 and 2,331 were either BA.4 or BA.5 cases. There was no evidence of reduced VE against hospitalisation for BA.4 or BA.5 as compared to BA.2. The incremental VE was 56.8% (95% C.I.; 24.0-75.4%), 59.9% (95% C.I.; 45.6-70.5%) and 52.4% (95% C.I.; 43.2-60.1%) for BA.4, BA.5 and BA.2, respectively, at 2 to 14 weeks after a third or fourth dose. VE against hospitalisation with BA.4/5 or BA.2 was slightly higher for the mRNA-1273 booster than the BNT162b2 booster at all time-points investigated, but confidence intervals overlapped. These data provide reassuring evidence of the protection conferred by the current vaccines against severe disease with BA.4 and BA.5.
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BackgroundLittle is known about the protection following prior infection with different SARS-CoV-2 variants, COVID-19 vaccination, and a combination of the two (hybrid immunity) in adolescents. MethodsWe used national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England to estimate protection following previous infection and vaccination against symptomatic PCR-confirmed delta and omicron BA.1/BA.2 variants in 11-17-year-olds using a test-negative case-control design. FindingsBy 31 March 2022, 63.6% of 16-17-year-olds and 48.2% of 12-15-year-olds had received [≥]1 COVID-19 mRNA vaccine dose.Between 08 August 2021 and 31 March 2022, 1,161,704 SARS-CoV-2 PCR-tests were successfully linked to COVID-19 vaccination status. In unvaccinated adolescents, prior infection with wildtype, alpha or delta provided greater protection against subsequent delta infection than subsequent omicron; prior omicron infection provided had the highest protection against omicron reinfection (59.3%; 95%CI: 46.7-69.0). In infection-naive adolescents, vaccination provided lower protection against symptomatic omicron infection than delta, peaking at 64.5% (95%CI; 63.6-65.4) 2-14 days after dose two and 62.9% (95%CI; 60.5-65.1) 2-14 weeks after dose three, with rapidly waning protection after each dose. Previously infected and vaccinated adolescents had the highest protection, irrespective of primary infecting SARS-CoV-2 strain. The highest protection against omicron was observed in vaccinated adolescents with prior omicron infection, reaching 96.4% (95%CI, 84.4-99.1) at 15-24 weeks post dose two. InterpretationAll variants provide some protection against symptomatic reinfection and vaccination adds to protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provides the most robust protection. FundingNone Research in contextO_ST_ABSEvidence before this studyC_ST_ABSWe have previously reported COVID-19 vaccine effectiveness in previously uninfected adolescents. There are, however, limited data on the protection offered by natural infection with different SARS-CoV-2 variants, and the added value of vaccination in previously-infected adolescents. Most studies have focused on adults and show significant protection from previous infection against re-infection with pre-omicron variants, but lower protection against omicron variants, with hybrid immunity providing the most robust protection. Added value of this studyUsing national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England, we were able to estimate protection afforded by previous infection, vaccination, and a combination of the two using a test-negative case-control design against PCR-confirmed symptomatic COVID-19. We found that protection against symptomatic infection with the delta variant was greater than protection against symptomatic omicron infection in those previously infected with wild-type, alpha or delta variants. Similar trends were observed in previously uninfected but vaccinated individuals. Prior omicron infection along with vaccination provided the greatest protection against further omicron variant infections. Implications of all the available evidenceAll variants provide some protection against future SARS-CoV-2 infection, as does COVID-19 mRNA vaccination. Our findings demonstrate, for the first time in adolescents, the additional protection afforded by hybrid immunity. In the context of the UKs recent waves of omicron infections, our findings provide important evidence of only modest short-term protection against mild disease with omicron variants following vaccination. This has important implications for the consideration of future adolescent COVID-19 vaccination and booster programmes.
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BackgroundDespite the potential widespread global use of the ChAdOx1-S booster, to date there are no published data on the real-world effectiveness. VE studies have found one and two doses of the ChAdOx1-S vaccine to be highly effective, and clinical trial data have demonstrated enhanced immunity following a ChAdOx1-S booster. In England, some individuals received a ChAdOx1-S booster where vaccination with mRNA vaccines was clinically contraindicated. MethodsThe demographic characteristics of those who received a ChAdOx1-S booster were compared to those who received a BNT162b2 booster. A test-negative case control design was used to estimate vaccine effectiveness of the ChAdOx1-S booster against symptomatic disease and hospitalisation in England. FindingsThose who received a ChAdOx1-S booster 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 CEV group (adjusted OR 1.84 (1.79-1.89)) or severely immunosuppressed (adjusted OR 2.05 (1.96-2.13)). Protection against symptomatic disease in those aged 65 years and older peaked at 66.1% (16.6 to 86.3%) and 68.5% (65.7 to 71.2%) amongst those who received the ChAdOx1-S and BNT162b2 booster vaccines, respectively. Protection waned to 44.5% (22.4 to 60.2%) and 54.1% (50.5 to 57.5%) after 5-9 weeks. Protection against hospitalisation following Omicron infection peaked at 82.3% (64.2 to 91.3%) after receiving a ChAdOx1-S booster, as compared to 90.9% (88.7 to 92.7%) for those who received a BNT162b2 booster. InterpretationDifferences in the population boosted with ChAdOx1-S in England renders direct comparison of vaccine effectiveness by manufacturer challenging. Nonetheless, this study supports the use of the ChAdOx1-S booster for protection against severe disease with COVID-19 in settings that have not yet offered booster doses and suggests that those who received ChAdOx1-S as a booster in England do not require re-vaccination ahead of others. FundingUKHSA
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BackgroundThe omicron (B.1.1.529) variant has been associated with reduced vaccine effectiveness (VE) against infection and mild disease with rapid waning, even after a third dose, nevertheless omicron has also been associated with milder disease than previous variants. With previous variants protection against severe disease has been substantially higher than protection against infection. MethodsWe used a test-negative case-control design to estimate VE against hospitalisation with the omicron and delta variants using community and in hospital testing linked to hospital records. As a milder disease, there may be an increasing proportion of hospitalised individuals with Omicron as an incidental finding. We therefore investigated the impact of using more specific and more severe hospitalisation indicators on VE. ResultsAmong 18-64 year olds using all Covid-19 cases admitted via emergency care VE after a booster peaked at 82.4% and dropped to 53.6% by 15+ weeks after the booster; using all admissions for >= 2 days stay with a respiratory code in the primary diagnostic field VE ranged from 90.9% down to 67.4%; further restricting to those on oxygen/ventilated/on intensive care VE ranged from 97.1% down to 75.9%. Among 65+ year olds the equivalent VE estimates were 92.4% down to 76.9%; 91.3% down to 85.3% and 95.8% down to 86.8%. ConclusionsWith generally milder disease seen with Omicron, in particular in younger adults, contamination of hospitalisations with incidental cases is likely to reduce VE estimates against hospitalisation. VE estimates improve and waning and waning is more limited when definitions of hospitalisation that are more specific to severe respiratory disease are used.
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The BA.1 sub-lineage of the Omicron (B.1.1.529) variant, first detected in the UK in mid-November 2021, rapidly became the dominant strain partly due to reduced vaccine effectiveness. An increase in a second Omicron sub-lineage BA.2 was observed in early January 2022. In this study we use a test-negative case control study design to estimate vaccine effectiveness against symptomatic disease with BA.1 and BA.2 after one or two doses of BNT162b2, ChAdOx1-S or mRNA-1273, and after booster doses of BNT162b2 or mRNA-1273 during a period of co-circulation. Overall, there was no evidence that vaccine effectiveness against symptomatic disease is reduced following infection with the BA.2 sub-lineage as compared to BA.1. Furthermore, similar rates of waning were observed after the second and booster dose for each sub-lineage. These data provide reassuring evidence of the effectiveness of the vaccines currently in use against symptomatic disease caused by BA.2.
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BackgroundA rapid increase in cases due to the SARS-CoV-2 Omicron (B.1.1.529) variant in highly vaccinated populations has raised concerns about the effectiveness of current vaccines. MethodsWe used a test-negative case-control design to estimate vaccine effectiveness (VE) against symptomatic disease caused by the Omicron and Delta variants in England. VE was calculated after primary immunisation with two BNT162b2 or ChAdOx1 doses, and at 2+ weeks following a BNT162b2 booster. ResultsBetween 27 November and 06 December 2021, 581 and 56,439 eligible Omicron and Delta cases respectively were identified. There were 130,867 eligible test-negative controls. There was no effect against Omicron from 15 weeks after two ChAdOx1 doses, while VE after two BNT162b2 doses was 88.0% (95%CI: 65.9 to 95.8%) 2-9 weeks after dose 2, dropping to between 34 and 37% from 15 weeks post dose 2.From two weeks after a BNT162b2 booster, VE increased to 71.4% (95%CI: 41.8 to 86.0%) for ChAdOx1 primary course recipients and 75.5% (95%CI: 56.1 to 86.3%) for BNT162b2 primary course recipients. For cases with Delta, VE was 41.8% (95%CI: 39.4-44.1%) at 25+ weeks after two ChAdOx1 doses, increasing to 93.8% (95%CI: 93.2-94.3%) after a BNT162b2 booster. With a BNT162b2 primary course, VE was 63.5% (95%CI: 61.4 to 65.5%) 25+ weeks after dose 2, increasing to 92.6% (95%CI: 92.0-93.1%) two weeks after the booster. ConclusionsPrimary immunisation with two BNT162b2 or ChAdOx1 doses provided no or limited protection against symptomatic disease with the Omicron variant. Boosting with BNT162b2 following either primary course significantly increased protection.
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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.
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BackgroundIn September 2021, the UK Government introduced a booster programme targeting individuals over 50 and those in a clinical risk group. Individuals were offered either a full dose of the BNT162b2 (Comirnaty, Pfizer-BioNTech) vaccine or a half dose of the mRNA-1273 (Spikevax, Moderna) vaccine, irrespective of the vaccine received as the primary course MethodsWe used a test-negative case-control design to estimate the Vaccine Effectiveness (VE) of the booster dose BNT162b2 (Comirnaty, Pfizer-BioNTech) in those aged over 50 against symptomatic disease in post booster time intervals compared to individuals at least 140 days post a second dose with no booster dose recorded. In a secondary analysis, we also compared to unvaccinated individuals and to the 2 to 6 day period after a booster dose was received. Analyses were stratified by which primary doses had been received and any mixed primary courses were excluded. ResultsThe relative VE estimate in the 14 days after the BNT162b2 (Comirnaty, Pfizer-BioNTech) booster dose, compared to individuals that received a two-dose primary course, was 87.4 (95% confidence interval 84.9-89.4) in those individuals who received two doses ChAdOx1-S (Vaxzevria, AstraZeneca) as a primary course and 84.4 (95% confidence interval 82.8-85.8) in those individuals who received two doses of BNT162b2 (Comirnaty, Pfizer-BioNTech) as a primary course. Using the 2-6 day period post the booster dose as the baseline gave similar results. The absolute VE from 14 days after the booster, using the unvaccinated baseline, was 93.1(95% confidence interval 91.7-94.3) in those with ChAdOx1-S (Vaxzevria, AstraZeneca) as their primary course and 94.0 (93.4-94.6) for BNT162b2 (Comirnaty, Pfizer-BioNTech) as their primary course. ConclusionsOur study provides real world evidence of significant increased protection from the booster vaccine dose against symptomatic disease in those aged over 50 year of age irrespective of which primary course was received.
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Serological surveillance studies sometimes use presence of anti-nucleocapsid antibody as a marker of natural SARS-CoV-2 infection. We explore seroconversion rates and antibody levels following Alpha and Delta variant infections, and vaccine breakthrough infections. We find lower seroconversion rates particularly following Alpha-variant vaccine breakthrough infections. We re-evaluate assay performance with a mix of past waned infections and recent breakthrough infections, that is relevant to current serological surveillance.
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In England, the National Immunisation Management System (NIMS) has been used to deliver COVID-19 vaccinations across England, monitor vaccine coverage, and assess vaccine effectiveness and safety. The NIMS was developed by a joint collaboration between a range of health and digital government agencies. Vaccinations delivered at large vaccination sites, pharmacies, hospitals and in primary care are entered on a point of care application which is verified using the unique NHS number in a centralised system containing information for everyone resident and registered with a GP in England. Vaccination details and additional data from hospital and GP records (such as priority groups) are sent to NHS Digital for data linkage. The NIMS constantly receives updated details from NHS Digital for all individuals and these data are provided to Public Health England (PHE) in a secure environment. PHE primarily use the NIMS for vaccine coverage, vaccine effectiveness and safety. Daily access to individual-level vaccine data has allowed PHE to rapidly and accurately estimate vaccine coverage and provide some of the worlds first vaccine effectiveness estimates. Other countries evaluating the roll-out and effect of COVID-19 vaccine programmes should consider a vaccine register or immunisation information system similar to the NIMS.
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BackgroundCOVID-19 vaccines have been used for 9 months in the UK. Real world data have demonstrated the vaccines to be highly effective against COVID-19, severe disease and death. Here, we estimate vaccine effectiveness over time since the second dose of Comirnaty, Vaxzevria and Spikevax in England. MethodsWe used a test-negative case-control design to estimate vaccine effectiveness against symptomatic disease, hospitalisation and mortality by age, comorbidity status and over time after the second dose to investigate waning separately for Alpha and Delta variants. ResultsVaccine effectiveness against symptomatic disease peaked in the early weeks after the second dose and then fell to 47.3 (95% CI 45 to 49.6) and 69.7 (95% CI 68.7 to 70.5) by 20+ weeks against the Delta variant for Vaxzevria and Comirnaty, respectively. Waning of vaccine effectiveness was greater for 65+ year-olds compared to 40-64 year-olds. Vaccine effectiveness fell less against hospitalisations to 77.0 (70.3 to 82.3) and 92.7 (90.3 to 94.6) beyond 20 weeks post-vaccination and 78.7 (95% CI 52.7 to 90.4) and 90.4 (95% CI 85.1 to 93.8) against death for Vaxzevria and Comirnaty, respectively. Greater waning was observed among 65+ year-olds in a clinically extremely vulnerable group and 40-64-year olds with underlying medical conditions compared to healthy adults. ConclusionsWe observed limited waning in vaccine effectiveness against hospitalisation and death more than 20 weeks post-vaccination with Vaxzevria or Comirnaty. Waning was greater in older adults and those in a clinical risk group, suggesting that these individuals should be prioritised for booster doses.
