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1.
PLoS Med ; 20(6): e1004245, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37285378

RESUMO

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.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Miocardite , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Vacina de mRNA-1273 contra 2019-nCoV , Vacina BNT162 , ChAdOx1 nCoV-19 , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Inglaterra/epidemiologia , Vacinas de mRNA , Miocardite/epidemiologia , Miocardite/etiologia , SARS-CoV-2 , Vacinação/efeitos adversos
2.
PLoS Med ; 18(2): e1003523, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33600451

RESUMO

BACKGROUND: The Eliminate Yellow fever Epidemics (EYE) strategy was launched in 2017 in response to the resurgence of yellow fever in Africa and the Americas. The strategy relies on several vaccination activities, including preventive mass vaccination campaigns (PMVCs). However, to what extent PMVCs are associated with a decreased risk of outbreak has not yet been quantified. METHODS AND FINDINGS: We used the self-controlled case series (SCCS) method to assess the association between the occurrence of yellow fever outbreaks and the implementation of PMVCs at the province level in the African endemic region. As all time-invariant confounders are implicitly controlled for in the SCCS method, this method is an alternative to classical cohort or case-control study designs when the risk of residual confounding is high, in particular confounding by indication. The locations and dates of outbreaks were identified from international epidemiological records, and information on PMVCs was provided by coordinators of vaccination activities and international funders. The study sample consisted of provinces that were both affected by an outbreak and targeted for a PMVC between 2005 and 2018. We compared the incidence of outbreaks before and after the implementation of a PMVC. The sensitivity of our estimates to a range of assumptions was explored, and the results of the SCCS method were compared to those obtained through a retrospective cohort study design. We further derived the number of yellow fever outbreaks that have been prevented by PMVCs. The study sample consisted of 33 provinces from 11 African countries. Among these, the first outbreak occurred during the pre-PMVC period in 26 (79%) provinces, and during the post-PMVC period in 7 (21%) provinces. At the province level, the post-PMVC period was associated with an 86% reduction (95% CI 66% to 94%, p < 0.001) in the risk of outbreak as compared to the pre-PMVC period. This negative association between exposure to PMVCs and outbreak was robustly observed across a range of sensitivity analyses, especially when using quantitative estimates of vaccination coverage as an alternative exposure measure, or when varying the observation period. In contrast, the results of the cohort-style analyses were highly sensitive to the choice of covariates included in the model. Based on the SCCS results, we estimated that PMVCs were associated with a 34% (95% CI 22% to 45%) reduction in the number of outbreaks in Africa from 2005 to 2018. A limitation of our study is the fact that it does not account for potential time-varying confounders, such as changing environmental drivers of yellow fever and possibly improved disease surveillance. CONCLUSIONS: In this study, we provide new empirical evidence of the high preventive impact of PMVCs on yellow fever outbreaks. This study illustrates that the SCCS method can be advantageously applied at the population level in order to evaluate a public health intervention.


Assuntos
Surtos de Doenças/prevenção & controle , Cobertura Vacinal/estatística & dados numéricos , Febre Amarela/epidemiologia , Febre Amarela/prevenção & controle , América , Estudos de Casos e Controles , Humanos , Programas de Imunização/métodos , Incidência
3.
Pharmacoepidemiol Drug Saf ; 30(6): 671-684, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33715267

RESUMO

PURPOSE: Consensus is needed on conceptual foundations, terminology and relationships among the various self-controlled "trigger" study designs that control for time-invariant confounding factors and target the association between transient exposures (potential triggers) and abrupt outcomes. The International Society for Pharmacoepidemiology (ISPE) funded a working group of ISPE members to develop guidance material for the application and reporting of self-controlled study designs, similar to Standards of Reporting Observational Epidemiology (STROBE). This first paper focuses on navigation between the types of self-controlled designs to permit a foundational understanding with guiding principles. METHODS: We leveraged a systematic review of applications of these designs, that we term Self-controlled Crossover Observational PharmacoEpidemiologic (SCOPE) studies. Starting from first principles and using case examples, we reviewed outcome-anchored (case-crossover [CCO], case-time control [CTC], case-case-time control [CCTC]) and exposure-anchored (self-controlled case-series [SCCS]) study designs. RESULTS: Key methodological features related to exposure, outcome and time-related concerns were clarified, and a common language and worksheet to facilitate the design of SCOPE studies is introduced. CONCLUSIONS: Consensus on conceptual foundations, terminology and relationships among SCOPE designs will facilitate understanding and critical appraisal of published studies, as well as help in the design, analysis and review of new SCOPE studies. This manuscript is endorsed by ISPE.


Assuntos
Farmacoepidemiologia , Projetos de Pesquisa , Estudos de Casos e Controles , Estudos Cross-Over , Humanos , Fatores de Tempo
4.
Stat Med ; 37(4): 643-658, 2018 02 20.
Artigo em Inglês | MEDLINE | ID: mdl-29094391

RESUMO

We describe some simple techniques for investigating 2 key assumptions of the self-controlled case series (SCCS) method, namely, that events do not influence subsequent exposures and that events do not influence the length of observation periods. For each assumption, we propose some simple tests based on the standard SCCS model, along with associated graphical displays. The methods also enable the user to investigate the robustness of the results obtained using the standard SCCS model to failure of assumptions. The proposed methods are investigated by simulations and applied to data on measles, mumps and rubella vaccine, and antipsychotics.


Assuntos
Modelos Estatísticos , Antipsicóticos/efeitos adversos , Bioestatística , Estudos de Coortes , Simulação por Computador , Demência/complicações , Humanos , Funções Verossimilhança , Vacina contra Sarampo-Caxumba-Rubéola/efeitos adversos , Púrpura Trombocitopênica Idiopática/etiologia , Reprodutibilidade dos Testes , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Fatores de Tempo
5.
Biom J ; 60(6): 1110-1120, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30284323

RESUMO

The self-controlled case series method assumes that adverse outcomes arise according to a non-homogeneous Poisson process. This implies that it is applicable to independent recurrent outcomes. However, the self-controlled case series method may also be applied to unique, non-recurrent outcomes or first outcomes only, in the limit where these become rare. We investigate this rare outcome assumption when the self-controlled case series method is applied to non-recurrent outcomes. We study this requirement analytically and by simulation, and quantify what is meant by 'rare' in this context. In simulations we also apply the self-controlled risk interval design, a special case of the self-controlled case series design. To illustrate, we extract data on the incidence rate of some recurrent and non-recurrent outcomes within a defined study population to check whether outcomes are sufficiently rare for the rare outcome assumption to hold when applying the self-controlled case series method to first or unique outcomes. The main findings are that the relative bias should be no more than 5% when the cumulative incidence over total time observed is less than 0.1 per individual. Inclusion of age (or calendar time) effects will further reduce bias. Designs that begin observation with exposure maximise bias, whereas little or no bias will be apparent when there is no time trend in the distribution of exposures, or when exposure is central within time observed.


Assuntos
Biometria/métodos , Estudos Epidemiológicos , Viés , Pré-Escolar , Humanos , Lactente , Recém-Nascido , Funções Verossimilhança , Distribuição de Poisson , Recidiva , Convulsões Febris/epidemiologia
6.
Stat Med ; 36(19): 3022-3038, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28470682

RESUMO

The self-controlled case series (SCCS) method is an alternative to study designs such as cohort and case control methods and is used to investigate potential associations between the timing of vaccine or other drug exposures and adverse events. It requires information only on cases, individuals who have experienced the adverse event at least once, and automatically controls all fixed confounding variables that could modify the true association between exposure and adverse event. Time-varying confounders such as age, on the other hand, are not automatically controlled and must be allowed for explicitly. The original SCCS method used step functions to represent risk periods (windows of exposed time) and age effects. Hence, exposure risk periods and/or age groups have to be prespecified a priori, but a poor choice of group boundaries may lead to biased estimates. In this paper, we propose a nonparametric SCCS method in which both age and exposure effects are represented by spline functions at the same time. To avoid a numerical integration of the product of these two spline functions in the likelihood function of the SCCS method, we defined the first, second, and third integrals of I-splines based on the definition of integrals of M-splines. Simulation studies showed that the new method performs well. This new method is applied to data on pediatric vaccines. Copyright © 2017 John Wiley & Sons, Ltd.


Assuntos
Biometria/métodos , Funções Verossimilhança , Medição de Risco/métodos , Fatores Etários , Teorema de Bayes , Simulação por Computador , Fatores de Confusão Epidemiológicos , Humanos , Análise de Regressão , Vacinas
7.
Biom J ; 58(3): 607-22, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26494534

RESUMO

The self-controlled case series (SCCS) method, commonly used to investigate the safety of vaccines, requires information on cases only and automatically controls all age-independent multiplicative confounders, while allowing for an age-dependent baseline incidence. Currently, the SCCS method represents the time-varying exposures using step functions with pre-determined cut points. A less prescriptive approach may be beneficial when the shape of the relative risk function associated with exposure is not known a priori, especially when exposure effects can be long-lasting. We therefore propose to model exposure effects using flexible smooth functions. Specifically, we used a linear combination of cubic M-splines which, in addition to giving plausible shapes, avoids the integral in the log-likelihood function of the SCCS model. The methods, though developed specifically for vaccines, are applicable more widely. Simulations showed that the new approach generally performs better than the step function method. We applied the new method to two data sets, on febrile convulsion and exposure to MMR vaccine, and on fractures and thiazolidinedione use.


Assuntos
Biometria/métodos , Modelos Estatísticos , Vacinas/normas , Humanos , Incidência , Funções Verossimilhança , Projetos de Pesquisa , Risco
8.
Stat Med ; 33(4): 639-49, 2014 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-24038284

RESUMO

The self-controlled case series method, commonly used to investigate potential associations between vaccines and adverse events, requires information on cases only and automatically controls all age-independent multiplicative confounders while allowing for an age-dependent baseline incidence. In the parametric version of the method, we modelled the age-specific relative incidence by using a piecewise constant function, whereas in the semiparametric version, we left it unspecified. However, mis-specification of age groups in the parametric version can lead to biassed estimates of exposure effect, and the semiparametric approach runs into computational problems when the number of cases in the study is moderately large. We, thus, propose to use a penalized likelihood approach where the age effect is modelled using splines. We use a linear combination of cubic M-splines to approximate the age-specific relative incidence and integrated splines for the cumulative relative incidence. We conducted a simulation study to evaluate the performance of the new approach and its efficiency relative to the parametric and semiparametric approaches. Results show that the new approach performs equivalently to the existing methods when the sample size is small and works well for large data sets. We applied the new spline-based approach to data on febrile convulsions and paediatric vaccines. Co


Assuntos
Funções Verossimilhança , Modelos Estatísticos , Fatores Etários , Simulação por Computador , Vacina contra Difteria, Tétano e Coqueluche/administração & dosagem , Feminino , Humanos , Incidência , Lactente , Masculino , Vacina contra Sarampo-Caxumba-Rubéola/administração & dosagem , Convulsões Febris/etiologia , Vacinação/efeitos adversos
10.
Vaccine ; 42(7): 1656-1664, 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38342716

RESUMO

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.


Assuntos
Serviços Médicos de Emergência , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza , Influenza Humana , Adulto , Criança , Pré-Escolar , Humanos , Influenza Humana/epidemiologia , Influenza Humana/prevenção & controle , Estudos de Casos e Controles , Estações do Ano , Vírus da Influenza A Subtipo H3N2 , Vacinas contra COVID-19 , Pandemias/prevenção & controle , Vacinas contra Influenza/uso terapêutico , Inglaterra/epidemiologia , Vacinação , Atenção Primária à Saúde
11.
Influenza Other Respir Viruses ; 18(5): e13295, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38744684

RESUMO

BACKGROUND: The 2022/23 influenza season in the United Kingdom saw the return of influenza to prepandemic levels following two seasons with low influenza activity. The early season was dominated by A(H3N2), with cocirculation of A(H1N1), reaching a peak late December 2022, while influenza B circulated at low levels during the latter part of the season. From September to March 2022/23, influenza vaccines were offered, free of charge, to all aged 2-13 (and 14-15 in Scotland and Wales), adults up to 49 years of age with clinical risk conditions and adults aged 50 and above across the mainland United Kingdom. METHODS: End-of-season adjusted vaccine effectiveness (VE) estimates against sentinel primary-care attendance for influenza-like illness, where influenza infection was laboratory confirmed, were calculated using the test negative design, adjusting for potential confounders. METHODS: Results In the mainland United Kingdom, end-of-season VE against all laboratory-confirmed influenza for all those > 65 years of age, most of whom received adjuvanted quadrivalent vaccines, was 30% (95% CI: -6% to 54%). VE for those aged 18-64, who largely received cell-based vaccines, was 47% (95% CI: 37%-56%). Overall VE for 2-17 year olds, predominantly receiving live attenuated vaccines, was 66% (95% CI: 53%-76%). CONCLUSION: The paper provides evidence of moderate influenza VE in 2022/23.


Assuntos
Vírus da Influenza A Subtipo H3N2 , Vírus da Influenza B , Vacinas contra Influenza , Influenza Humana , Atenção Primária à Saúde , Eficácia de Vacinas , Humanos , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Pessoa de Meia-Idade , Adolescente , Adulto , Atenção Primária à Saúde/estatística & dados numéricos , Reino Unido/epidemiologia , Idoso , Adulto Jovem , Criança , Feminino , Masculino , Pré-Escolar , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza B/imunologia , Vírus da Influenza A Subtipo H1N1/imunologia , Estações do Ano , Vacinação/estatística & dados numéricos
12.
Am J Epidemiol ; 177(5): 474-86, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23403987

RESUMO

In this paper, we propose new methods for investigating the extent of heterogeneity in effective contact rates relevant to the transmission of infections. These methods exploit the correlations between ages at infection for different infections within individuals. The methods are developed for serological surveys, which provide accessible individual data on several infections, and are applied to a wide range of infections. We find that childhood infections are often highly correlated within individuals in early childhood, with the correlations persisting into adulthood only for infections sharing a transmission route. We discuss 2 applications of the methods: 1) to making inferences about routes of transmission when these are unknown or uncertain and 2) to estimating epidemiologic parameters such as the basic reproduction number and the critical immunization threshold. Two examples of such applications are presented: elucidating the transmission route of polyomaviruses BK and JC and estimating the basic reproduction number and critical immunization coverage of varicella-zoster infection in Belgium, Italy, Poland, and England and Wales. We speculate that childhood correlations stem from confounding of different transmission routes and represent heterogeneity in childhood circumstances, notably nursery-school attendance. In contrast, it is suggested that correlations in adulthood are route-specific.


Assuntos
Transmissão de Doença Infecciosa , Métodos Epidemiológicos , Vacinação/estatística & dados numéricos , Número Básico de Reprodução , Humanos , Modelos Biológicos , Estudos Soroepidemiológicos , Testes Sorológicos , Estatística como Assunto
13.
Pharmacoepidemiol Drug Saf ; 22(8): 819-25, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23625875

RESUMO

PURPOSE: The assumption that the occurrence of outcome event must not alter subsequent exposure probability is critical for preserving the validity of the self-controlled case series (SCCS) method. This assumption is violated in scenarios in which the event constitutes a contraindication for exposure. In this simulation study, we compared the performance of the standard SCCS approach and two alternative approaches when the event-independent exposure assumption was violated. METHODS: Using the 2009 H1N1 and seasonal influenza vaccines and Guillain-Barré syndrome as a model, we simulated a scenario in which an individual may encounter multiple unordered exposures and each exposure may be contraindicated by the occurrence of outcome event. The degree of contraindication was varied at 0%, 50%, and 100%. The first alternative approach used only cases occurring after exposure with follow-up time starting from exposure. The second used a pseudo-likelihood method. RESULTS: When the event-independent exposure assumption was satisfied, the standard SCCS approach produced nearly unbiased relative incidence estimates. When this assumption was partially or completely violated, two alternative SCCS approaches could be used. While the post-exposure cases only approach could handle only one exposure, the pseudo-likelihood approach was able to correct bias for both exposures. CONCLUSIONS: Violation of the event-independent exposure assumption leads to an overestimation of relative incidence which could be corrected by alternative SCCS approaches. In multiple exposure situations, the pseudo-likelihood approach is optimal; the post-exposure cases only approach is limited in handling a second exposure and may introduce additional bias, thus should be used with caution.


Assuntos
Síndrome de Guillain-Barré/epidemiologia , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Projetos de Pesquisa , Viés , Simulação por Computador , Contraindicações , Síndrome de Guillain-Barré/etiologia , Humanos , Incidência , Vírus da Influenza A Subtipo H1N1 , Vacinas contra Influenza/administração & dosagem , Funções Verossimilhança , Farmacoepidemiologia , Probabilidade , Fatores de Tempo
14.
Vaccine X ; 15: 100418, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38090643

RESUMO

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.

15.
J Infect ; 87(4): 315-327, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37579793

RESUMO

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


Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Vacina BNT162 , ChAdOx1 nCoV-19 , Estudos de Coortes , Eficácia de Vacinas , SARS-CoV-2 , Hospitalização , Atenção Primária à Saúde
16.
J Infect ; 84(5): 692-700, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35131335

RESUMO

BACKGROUND: There are limited data on immune responses to heterologous COVID-19 immunisation schedules, especially following an extended ≥12-week interval between doses. METHODS: SARS-CoV-2 infection-naïve and previously-infected adults receiving ChAd-BNT (ChAdOx1 nCoV-19, AstraZeneca followed by BNT162b2, Pfizer-BioNTech) or BNT-ChAd as part of the UK national immunisation programme provided blood samples at 30 days and 12 weeks after their second dose. Geometric mean concentrations (GMC) of anti-SARS-CoV-2 spike (S-antibody) and nucleoprotein (N-antibody) IgG antibodies and geometric mean ratios (GMR) were compared with a contemporaneous cohort receiving homologous ChAd-ChAd or BNT-BNT. RESULTS: During March-October 2021, 75,827 individuals were identified as having received heterologous vaccination, 9,489 invited to participate, 1,836 responded (19.3%) and 656 were eligible. In previously-uninfected adults, S-antibody GMC at 30 days post-second dose were lowest for ChAd-ChAd (862 [95% CI, 694 - 1069]) and significantly higher for ChAd-BNT (6233 [5522-7035]; GMR 6.29; [5.04-7.85]; p<0.001), BNT-ChAd (4776 [4066-5610]; GMR 4.55 [3.56-5.81]; p<0.001) and BNT-BNT (5377 [4596-6289]; GMR 5.66 [4.49-7.15]; p<0.001). By 12 weeks after dose two, S-antibody GMC had declined in all groups and remained significantly lower for ChAd-ChAd compared to ChAd-BNT (GMR 5.12 [3.79-6.92]; p<0.001), BNT-ChAd (GMR 4.1 [2.96-5.69]; p<0.001) and BNT-BNT (GMR 6.06 [4.32-8.50]; p<0.001). Previously infected adults had higher S-antibody GMC compared to infection-naïve adults at all time-points and with all vaccine schedules. CONCLUSIONS: These real-world findings demonstrate heterologous schedules with adenoviral-vector and mRNA vaccines are highly immunogenic and may be recommended after a serious adverse reaction to one vaccine product, or to increase programmatic flexibility where vaccine supplies are constrained.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Formação de Anticorpos , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , ChAdOx1 nCoV-19 , Inglaterra , Humanos , Imunoglobulina G , Vacinação
17.
J Infect ; 84(5): 675-683, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-34990709

RESUMO

Background COVID-19 vaccines approved in the UK are highly effective in general population cohorts, however, data on effectiveness amongst individuals with clinical conditions that place them at increased risk of severe disease are limited. Methods We used GP electronic health record data, sentinel virology swabbing and antibody testing within a cohort of 712 general practices across England to estimate vaccine antibody response and vaccine effectiveness against medically attended COVID-19 amongst individuals in clinical risk groups using cohort and test-negative case control designs. Findings There was no reduction in S-antibody positivity in most clinical risk groups, however reduced S-antibody positivity and response was significant in the immunosuppressed group. Reduced vaccine effectiveness against clinical disease was also noted in the immunosuppressed group; after a second dose, effectiveness was moderate (Pfizer: 59.6%, 95%CI 18.0-80.1%; AstraZeneca 60.0%, 95%CI -63.6-90.2%). Interpretation In most clinical risk groups, immune response to primary vaccination was maintained and high levels of vaccine effectiveness were seen. Reduced antibody response and vaccine effectiveness were seen after 1 dose of vaccine amongst a broad immunosuppressed group, and second dose vaccine effectiveness was moderate. These findings support maximising coverage in immunosuppressed individuals and the policy of prioritisation of this group for third doses.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacina BNT162 , COVID-19/prevenção & controle , ChAdOx1 nCoV-19 , Humanos , Imunidade , SARS-CoV-2 , Eficácia de Vacinas
18.
Stat Med ; 30(6): 666-77, 2011 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-21337361

RESUMO

The self-controlled case series method (SCCS) was developed to analyze the association between a time-varying exposure and an outcome event. We consider penta- or hexavalent vaccination as the exposure and unexplained sudden unexpected death (uSUD) as the event. The special situation of multiple exposures and a terminal event requires adaptation of the standard SCCS method. This paper proposes a new adaptation, in which observation periods are truncated according to the vaccination schedule. The new method exploits known minimum spacings between successive vaccine doses. Its advantage is that it is very much simpler to apply than the method for censored, perturbed or curtailed post-event exposures recently introduced. This paper presents a comparison of these two SCCS methods by simulation studies and an application to a real data set. In the simulation studies, the age distribution and the assumed vaccination schedule were based on real data. Only small differences between the two SCCS methods were observed, although 50 per cent of cases could not be included in the analysis with the SCCS method with truncated observation periods. By means of a study including 300 uSUD, a 16-fold risk increase after the 4th dose could be detected with a power of at least 90 per cent. A general 2-fold risk increase after vaccination could be detected with a power of 80 per cent. Reanalysis of data from cases of the German case-control study on sudden infant death (GeSID) resulted in slightly higher point estimates using the SCCS methods than the odds ratio obtained by the case-control analysis.


Assuntos
Interpretação Estatística de Dados , Modelos Estatísticos , Morte Súbita do Lactente/imunologia , Vacinação/métodos , Vacinas/administração & dosagem , Vacinas/efeitos adversos , Estudos de Casos e Controles , Simulação por Computador , Humanos , Lactente
19.
J Infect ; 83(2): 237-279, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33989631

RESUMO

The COVID-19 vaccination programme commenced in England on 8th December 2020 primarily based on age; by 7th March 2021 approximately 93% of the English population aged 70+ years had received at least 1 dose of either the Pfizer BioNTech or AstraZeneca vaccines. Using a nucleoprotein assay that detects antibodies following natural infection only and a spike assay that detects infection and vaccine-induced responses, we aim to describe the impact of vaccination on SARS-CoV-2 antibody prevalence in English blood donors.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Idoso , Formação de Anticorpos , Doadores de Sangue , Inglaterra/epidemiologia , Pessoal de Saúde , Humanos , RNA Mensageiro , SARS-CoV-2 , Estudos Soroepidemiológicos , Vacinação
20.
J Infect ; 82(5): 162-169, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33766553

RESUMO

BACKGROUND: Antibody waning after SARS-CoV-2 infection may result in reduction in long-term immunity following natural infection and vaccination, and is therefore a major public health issue. We undertook prospective serosurveillance in a large cohort of healthy adults from the start of the epidemic in England. METHODS: Clinical and non-clinical healthcare workers were recruited across three English regions and tested monthly from March to November 2020 for SARS-CoV-2 spike (S) protein and nucleoprotein (N) antibodies using five different immunoassays. In positive individuals, antibody responses and long-term trends were modelled using mixed effects regression. FINDINGS: In total, 2246 individuals attended 12,247 visits and 264 were seropositive in ≥ 2 assays. Most seroconversions occurred between March and April 2020. The assays showed > 85% agreement for ever-positivity, although this changed markedly over time. Antibodies were detected earlier with Abbott (N) but declined rapidly thereafter. With the EuroImmun (S) and receptor-binding domain (RBD) assays, responses increased for 4 weeks then fell until week 12-16 before stabilising. For Roche (N), responses increased until 8 weeks, stabilised, then declined, but most remained above the positive threshold. For Roche (S), responses continued to climb over the full 24 weeks, with no sero-reversions. Predicted proportions sero-reverting after 52 weeks were 100% for Abbott, 59% (95% credible interval 50-68%) Euroimmun, 41% (30-52%) RBD, 10% (8-14%) Roche (N) < 2% Roche (S). INTERPRETATION: Trends in SARS-CoV-2 antibodies following infection are highly dependent on the assay used. Ongoing serosurveillance using multiple assays is critical for monitoring the course and long-term progression of SARS-CoV-2 antibodies.


Assuntos
COVID-19 , SARS-CoV-2 , Adulto , Anticorpos Antivirais , Formação de Anticorpos , Inglaterra , Pessoal de Saúde , Humanos , Estudos Prospectivos , Saúde Pública
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