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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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BackgroundThe SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources. MethodsOmicron 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 Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission. FindingsAnalysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16). InterpretationOur 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. FundingStudy funded by the UK Health Security Agency.
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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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BackgroundThe ability of SARS-CoV-2 vaccines to protect against infection and onward transmission determines whether immunisation can control global circulation. We estimated effectiveness of BNT162b2 and ChAdOx1 vaccines against acquisition and transmission of the Alpha and Delta variants in a prospective household study in England. MethodsAdult index cases in the community and their household contacts took oral-nasal swabs on days 1, 3 and 7 after enrolment. Swabs were tested by RT-qPCR with 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. FindingsBetween 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 1.64 times the risk (95% Credible Interval: 1.15 - 2.44) of transmission than Alpha; contacts older than 18 years were 1.19 times (1.04 - 1.52) more likely to acquire infection than children. Effectiveness of two doses of BNT162b2 against transmission of Delta was 31% (-3%, 61%) and 42% (14%, 69%) for ChAdOx1, similar to their effectiveness for Alpha. Protection against infection with Alpha was higher than for Delta, 71% (12%,95%) vs 24% (-2%, 64%) respectively for BNT162b2 and 26% (-39%, 73%) vs 14% (-5%, 46%) respectively for ChAdOx1. InterpretationBNT162b2 and ChAdOx1 reduce transmission of the Delta variant from breakthrough infections in the household setting though their protection against infection is low. FundingThis study was funded by the UK Health Security Agency (formerly Public Health England) as part of the COVID-19 response.
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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.
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ObjectiveTo determine characteristics associated with COVID-19 vaccine coverage among individuals aged 50 years and above in England since the beginning of the programme. DesignObservational cross-sectional study assessed by logistic regression and mean prevalence margins. SettingCOVID-19 vaccinations delivered in England from 08 December 2020 - 17 May 2021. Participants30,624,257/ 61,967,781 (49.4%) and 17,360,045/ 61,967,781 (28.1%) individuals in England were recorded as vaccinated in the National Immunisation Management System with a first dose and a second dose of a COVID-19 vaccine, respectively. InterventionsVaccination status with COVID-19 vaccinations. Main Outcome MeasuresProportion, adjusted odds ratios and mean prevalence margins for individuals not vaccinated with dose 1 among those aged 50-69 years old and dose 1 and 2 among those aged 70 years old and above. ResultsAmong individuals aged 50 years and above, Black/African/Caribbean ethnic group was the least likely of all ethnic groups to be vaccinated with dose 1 of the COVID-19 vaccine. However, among those aged 70 years and above, the odds of not having dose 2 was 5.53 (95% CI 5.42 to 5.63) and 5.36 (90% CI 5.29 to 5.43) greater among Pakistani and Black/African/Caribbean compared to White British ethnicity, respectively. The odds of not receiving dose 2 was 1.18 (95% CI 1.16 to 1.20) higher among individuals who lived in a care home compared to those who did not. This was the opposite to that observed for dose 1, where the odds of not being vaccinated was significantly higher among those not living in a care home (0.89 (95% CI 0.87 to 0.91)). ConclusionsWe found that there are characteristics associated with low COVID-19 vaccine coverage. Inequalities, such as ethnicity are a major contributor to suboptimal coverage and tailored interventions are required to improve coverage and protect the population from SARS-CoV-2. Article summaryO_ST_ABSStrengths and Limitations of this studyC_ST_ABSO_LIThis is the is the first study assessing characteristics associated with COVID-19 vaccine coverage for all individuals aged 50 years and above in England. C_LIO_LIThis study uses data from the National Immunisation Management System (NIMS) which is based on all individuals in England with a registered NHS number. C_LIO_LIThis centralised national system captures individual level data for both vaccination status and demographic characteristics and allows for linkage to other datasets such as health care worker and care home resident status. C_LIO_LIThis study does not include those without an NHS number and, therefore, it is possible we have underestimated the number of vaccines delivered and odds of not being vaccinated for characteristics such as ethnic groups where we have seen the greatest impact. C_LIO_LIResidual errors in data entry on the point of care apps at the vaccination sites may have also occurred, though these errors are not likely to be widespread. C_LI
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IntroductionIn January 2021, the UK decided to prioritise the delivery of the first dose of BNT162b2 (Pfizer/BioNTech) and AZD1222 (AstraZeneca) vaccines by extending the interval until the second dose up to 12 weeks. MethodsSerological responses were compared after BNT162b2 and AZD1222 vaccination with varying intervals in uninfected and previously-infected adults aged 50-89 years. These findings are evaluated against real-world national vaccine effectiveness (VE) estimates against COVID-19 in England. ResultsWe recruited 750 participants aged 50-89 years, including 126 (16.8%) with evidence of previous infection; 421 received BNT162b2 and 329 and AZD1222. For both vaccines, over 95% had seroconverted 35-55 days after dose one, and 100% seroconverted 7+ days after dose 2. Following a 65-84 day interval between two doses, geometric mean titres (GMTs) at 14-34 days were 6-fold higher for BNT162b2 (6703; 95%CI, 5887-7633) than AZD1222 (1093; 806-1483), which in turn were higher than those receiving BNT162b2 19-29 days apart (694; 540 - 893). For both vaccines, VE was higher across all age-groups from 14 days after dose two compared to one dose, but the magnitude varied with interval between doses. Higher two-dose VE was observed with >6 week intervals between BNT162b2 doses compared to the authorised 3-week schedule, including [≥]80 year-olds. ConclusionOur findings support the UK approach of prioritising the first dose of COVID-19 vaccines, with evidence of higher protection following extended schedules. Given global vaccine constraints, these results are relevant to policymakers, especially with highly transmissible variants and rising incidence in many countries. FundingPublic Health England
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BackgroundThe B.1.617.2 COVID-19 variant has contributed to the surge in cases in India and has now been detected across the globe, including a notable increase in cases in the UK. We estimate the effectiveness of the BNT162b2 and ChAdOx1 COVID-19 vaccines against this variant. MethodsA test negative case control design was used to estimate the effectiveness of vaccination against symptomatic disease with both variants over the period that B.1.617.2 began circulating with cases identified based on sequencing and S-gene target status. Data on all symptomatic sequenced cases of COVID-19 in England was used to estimate the proportion of cases with B.1.617.2 compared to the predominant strain (B.1.1.7) by vaccination status. ResultsEffectiveness was notably lower after 1 dose of vaccine with B.1.617.2 cases 33.5% (95%CI: 20.6 to 44.3) compared to B.1.1.7 cases 51.1% (95%CI: 47.3 to 54.7) with similar results for both vaccines. With BNT162b2 2 dose effectiveness reduced from 93.4% (95%CI: 90.4 to 95.5) with B.1.1.7 to 87.9% (95%CI: 78.2 to 93.2) with B.1.617.2. With ChAdOx1 2 dose effectiveness reduced from 66.1% (95% CI: 54.0 to 75.0) with B.1.1.7 to 59.8% (95%CI: 28.9 to 77.3) with B.1.617.2. Sequenced cases detected after 1 or 2 doses of vaccination had a higher odds of infection with B.1.617.2 compared to unvaccinated cases (OR 1.40; 95%CI: 1.13-1.75). ConclusionsAfter 2 doses of either vaccine there were only modest differences in vaccine effectiveness with the B.1.617.2 variant. Absolute differences in vaccine effectiveness were more marked with dose 1. This would support maximising vaccine uptake with two doses among vulnerable groups.
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We estimated risk of death in vaccinated compared to unvaccinated COVID-19 cases. Cases vaccinated with 1 dose of BNT162b2 had 44% reduced risk of death, 55% with 1 dose of ChAdOx1, and 69% with 2 doses of BNT162b2. This is on top of the protection provided against becoming a case.
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BackgroundVaccination constitutes the best long-term solution against Coronavirus Disease 2019 (COVID-19). Real-world immunogenicity data are sparse, particularly for ChAdOx1 and in populations with chronic conditions; and given the UKs extended dosing interval, it is also important to understand antibody responses in SARS-CoV-2-naive individuals following a single dose. MethodsAdults aged [≥]18 years from households enrolled in Virus Watch, a prospective community cohort study in England and Wales, provided capillary blood samples and self-reported vaccination status. Primary outcome variables were quantitative Spike total antibody levels (U/ml) and seropositivity to Spike ([≥]0.8 U/ml), as per Roches Elecsys Anti-SARS-CoV-2 S assay. Samples seropositive for Nucleocapsid, and samples taken prior to vaccination, were excluded. Outcomes were analysed by days since vaccination, vaccine type (BNT162b2 and ChAdOx1), and a range of self-reported demographic and clinical factors. Results8,517 vaccinated participants (median age 65 years [IQR: 58, 71]), contributed 13,232 samples (8,115 following ChAdOx1, 5,008 following BNT162b2). Seropositivity to Spike was 96.42% (95%CI 96, 96.79) at 28-34 days following a single dose, reaching 99.08% (97.8, 99.62) at 7-14 days after a second dose. Seropositivity rates, and Spike-antibody levels rose more quickly following the first dose of BNT162b2, however, were equivalent for both vaccines by 4 and 8 weeks, respectively. There was evidence of lower S-antibody levels with increasing age (p=0.0001). In partially vaccinated 65-79 year-olds, lower S-antibody levels were observed in men (25.9 vs 42.3 U/ml, p<0.0001), those with a chronic condition (33.0 vs 41.2 U/ml, p<0.0001), diabetes (22.32 vs 36.01 U/ml, p<0.0001), cardiovascular disease (32.1 vs 36.7 U/ml, p=0.0002), or history of cancer (30.1 vs 35.7 U/ml, p=0.0001), particularly those with haematological rather than solid organ cancer (7.48 vs 31.68 U/ml, p<0.0001), and those currently on immunosuppressive therapy (21.7 vs 35.6 U/ml, p<0.0001). Following a second dose, high S-antibody titres ([≥]250U/ml) were observed for nearly all individuals. InterpretationA single dose of either BNT162b2 or ChAdOx1 leads to high Spike seropositivity rates in SARS-CoV-2-naive individuals. However, observed disparities in antibody levels after the first dose by vaccine type, age, and comorbidities highlight the importance of ongoing non-pharmaceutical preventative measures such as social distancing, for partially vaccinated adults, particularly those who are older and more clinically vulnerable.
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BackgroundThe effectiveness of SARS-CoV-2 vaccines in frail older adults living in Long-Term Care Facilities (LTCFs) is uncertain. We estimated protective effects of the first dose of ChAdOx1 and BNT162b2 vaccines against infection in this population. MethodsCohort study comparing vaccinated and unvaccinated LTCF residents in England, undergoing routine asymptomatic testing (8 December 2020 - 15 March 2021). We estimated the relative hazard of PCR-positive infection using Cox proportional hazards regression, adjusting for age, sex, prior infection, local SARS-CoV-2 incidence, LTCF bed capacity, and clustering by LTCF. ResultsOf 10,412 residents (median age 86 years) from 310 LTCFs, 9,160 were vaccinated with either ChAdOx1 (6,138; 67%) or BNT162b2 (3,022; 33%) vaccines. A total of 670,628 person days and 1,335 PCR-positive infections were included. Adjusted hazard ratios (aHRs) for PCR-positive infection relative to unvaccinated residents declined from 28 days following the first vaccine dose to 0{middle dot}44 (0{middle dot}24, 0{middle dot}81) at 28-34 days and 0{middle dot}38 (0{middle dot}19, 0{middle dot}77) at 35-48 days. Similar effect sizes were seen for ChAdOx1 (aHR 0{middle dot}32 [0{middle dot}15-0{middle dot}66] and BNT162b2 (aHR 0{middle dot}35 [0{middle dot}17, 0{middle dot}71]) vaccines at 35-48 days. Mean PCR cycle threshold values were higher, implying lower infectivity, for infections [≥]28 days post-vaccination compared with those prior to vaccination (31{middle dot}3 vs 26{middle dot}6, p<0{middle dot}001). InterpretationThe first dose of BNT162b2 and ChAdOx1 vaccines was associated with substantially reduced SARS-CoV-2 infection risk in LTCF residents from 4 weeks to at least 7 weeks. FundingUK Government Department of Health and Social Care. Research in ContextO_ST_ABSEvidence before this studyC_ST_ABSWe conducted a systematic search for studies which evaluated SARS-CoV-2 vaccine effectiveness in residents of long-term care facilities (LTCFs) published between 01/01/2020 and 11/03/2021. We used variations of search terms for "COVID-19" AND "vaccine effectiveness" OR "vaccine efficacy" AND "care homes" OR "long term care facilities" OR "older people" on Ovid MEDLINE and MedRxiv. We identified one pre-print article regarding LTCFs in Denmark, which reported that a single dose of BNT162b was ineffective against SARS-CoV-2 infection in residents, however, participants received the second vaccine dose 24 days following the first dose on average, which is likely to be too soon to capture the protective effects of a single vaccine dose. Additionally, we identified two pre-print reports of studies evaluating vaccine effectiveness against symptomatic infection and hospitalisation amongst older adults in the community. The first of these found 81% vaccine effectiveness against COVID-19-related hospitalisation at 28-34 days following a single dose of BNT162b or ChAdOx1 in [≥]80-year-olds. The second of these found vaccine effectiveness against symptomatic infection of 60% at 28-34 days and 73% at 35+ days following a single dose of ChAdOx1 in [≥]70-year-olds. No studies were identified that focused on the effectiveness of a single vaccine dose against infection amongst LTCF residents at more than 4 weeks post-vaccination, a particularly important question in the context of the UK policy decision to extend the dose interval beyond 3 weeks. Added value of this studyWe conducted a prospective cohort study of 10,412 residents aged [≥]65 years, from 310 LTCFs across England, to investigate the protective effect of the first dose of the ChAdOx1 and BNT162b vaccines against SARS-CoV-2 infection in frail older adults. We retrieved results from routine monthly PCR testing, as well as outbreak and clinical testing for SARS-CoV-2, thereby capturing data on asymptomatic as well as symptomatic infections, which we linked to vaccination records. We estimated vaccine effectiveness to be 56% (19-76%) at 28-34 days, and 62% (23-81%) at 35-48 days following a single dose of ChAdOx1 or BNT162. Our findings suggest that the risk of SARS-CoV-2 infection is substantially reduced from 28 days following the first dose of either vaccine and that this effect is maintained for at least 7 weeks, with similar protection offered by both vaccine types. We also found that PCR cycle threshold (Ct) values, which are negatively associated with the ability to isolate virus, were significantly higher in infections occurring at [≥] 28days post vaccination compared to those occurring in the unvaccinated period, suggesting that vaccination may reduce onward transmission of SARS-CoV-2 in breakthrough infections. To the best of our knowledge, our findings constitute the first real-world evidence on vaccine effectiveness against infection for ChAdOx1, in any age group. We can also infer that both vaccines are effective against the B.1.1.7 variant, because our analysis period coincided with the rapid emergence of B.1.1.7 in England during the second wave of the pandemic. Implications of all the available evidenceOur findings add to the growing body of evidence on the protective effect of the BNT162b vaccines in residents of LTCFs and demonstrate the effectiveness of ChAdOx1 in this vulnerable population. Evaluating single-dose vaccine efficacy has become increasingly important in light of extended dosing intervals that have been implemented in order to maximise vaccine coverage across high-risk groups. Further work is required to evaluate the effectiveness of the first vaccine dose after 8-12 weeks, as well as following the second dose, and to evaluate the long-term impact of vaccination on SARS-CoV-2 infection, transmission and mortality in LTCFs. This will inform policy decisions regarding the ongoing need for disease control measures in LTCF such as visitor restrictions, which continue to have a detrimental impact on the wellbeing of residents, their relatives, and staff. Supplementary material attached.
RESUMO
ObjectivesTo estimate the real-world effectiveness of the Pfizer/BioNTech BNT162b2 vaccine and Astrazeneca ChAdOx1 vaccine against Confirmed COVID-19, hospitalisations and deaths. To estimate effectiveness on the UK variant of concern. DesignTest negative case control design SettingCommunity COVID-19 PCR testing in England ParticipantsAll adults in England aged 70 years and older (over 7.5 million). All COVID-19 testing in the community among eligible individuals who reported symptoms between 8th December 2020 and 19th February 2021 was included in the analysis. InterventionsOne and two doses of BNT162b2 vaccine. One dose of ChAdOx1 vaccine. Main outcome measuresSymptomatic PCR confirmed SARS-CoV-2 infection, hospitalisations and deaths with COVID-19. ResultsIndividuals aged >=80 years vaccinated with BNT162b2 prior to 4th January, had a higher odds of testing positive in the first 9 days after vaccination (odds ratio up to 1.48, 95%CI 1.23-1.77), indicating that those initially targeted had a higher underlying risk of infection. Vaccine effectiveness was therefore estimated relative to the baseline post-vaccination period. Vaccine effects were noted from 10-13 days after vaccination, reaching an effectiveness of 70% (95% CI 59-78%) from 28-34 days, then plateauing. From 14 days after the second dose a vaccine effectiveness of 89% (95%CI: 85-93%) was seen. Individuals aged >=70 years vaccinated from 4th January had a similar underlying risk of COVID-19 to unvaccinated individuals. With BNT162b2, vaccine effectiveness reached 61% (95%CI 51-69%) from 28-34 days after vaccination then plateaued. With the ChAdOx1 vaccine, vaccine effects were seen from 14-20 days after vaccination reaching an effectiveness of 60% (95%CI 41-73%) from 28-34 days and further increasing to 73% (95%CI 27-90%) from day 35 onwards. On top of the protection against symptomatic disease, cases who had been vaccinated with one dose of BNT162b2 had an additional 43% (95%CI 33-52%) lower risk of emergency hospitalisation and an additional 51% (95%CI 37-62%) lower risk of death. Cases who had been vaccinated with one dose of ChAdOx1 had an additional 37% (95% CI 3-59%) lower risk of emergency hospitalisation. There was insufficient follow-up to assess the effect of ChAdOx1 on mortality due to the later rollout of this vaccine. Combined with the effect against symptomatic disease, this indicates that a single dose of either vaccine is approximately 80% effective at preventing hospitalisation and a single dose of BNT162b2 is 85% effective at preventing death with COVID-19. ConclusionVaccination with either a single dose of BNT162b2 or ChAdOx1 COVID-19 vaccination was associated with a significant reduction in symptomatic SARS-CoV2 positive cases in older adults with even greater protection against severe disease. Both vaccines show similar effects. Protection was maintained for the duration of follow-up (>6 weeks). A second dose of BNT162b2 provides further protection against symptomatic disease but second doses of ChAdOx1 have not yet been rolled out in England. There is a clear effect of the vaccines against the UK variant of concern.
