ABSTRACT
BACKGROUND: In May 2020, the ACCESS (The vACCine covid-19 monitoring readinESS) project was launched to prepare real-world monitoring of COVID-19 vaccines. Within this project, this study aimed to generate background incidence rates of 41 adverse events of special interest (AESI) to contextualize potential safety signals detected following administration of COVID-19 vaccines. METHODS: A dynamic cohort study was conducted using a distributed data network of 10 healthcare databases from 7 European countries (Italy, Spain, Denmark, The Netherlands, Germany, France and United Kingdom) over the period 2017 to 2020. A common protocol (EUPAS37273), common data model, and common analytics programs were applied for syntactic, semantic and analytical harmonization. Incidence rates (IR) for each AESI and each database were calculated by age and sex by dividing the number of incident cases by the total person-time at risk. Age-standardized rates were pooled using random effect models according to the provenance of the events. FINDINGS: A total number of 63,456,074 individuals were included in the study, contributing to 211.7 million person-years. A clear age pattern was observed for most AESIs, rates also varied by provenance of disease diagnosis (primary care, specialist care). Thrombosis with thrombocytopenia rates were extremely low ranging from 0.06 to 4.53/100,000 person-years for cerebral venous sinus thrombosis (CVST) with thrombocytopenia (TP) and mixed venous and arterial thrombosis with TP, respectively. INTERPRETATION: Given the nature of the AESIs and the setting (general practitioners or hospital-based databases or both), background rates from databases that show the highest level of completeness (primary care and specialist care) should be preferred, others can be used for sensitivity. The study was designed to ensure representativeness to the European population and generalizability of the background incidence rates. FUNDING: The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE.
ABSTRACT
Introduction: Some COVID-19 vaccines (Moderna and Pfizer) have been associated with an elevated risk of myocarditis in younger adults. However, observational studies were unable to stratify by dose and had limited ability to evaluate the effect of adenovirus-based COVID-19 vaccines due to the limited distribution of these in their study populations [1-4]. Objective(s): Estimate the incidence rates (IR), rate differences (RD) and incidence rate ratios (IRR) of myocarditis and pericarditis before and after each dose of mRNA (Pfizer and Moderna) and adenovirusplatform (AstraZeneca and Janssen) COVID-19 vaccines. Method(s): We conducted a population-based cohort design with nested self-controlled risk interval (SCRI) study. Participants were followed from 1st January 2020 to 31st December 2021. Data were derived from healthcare data from five population-based data sources in four European countries: Italy, the Netherlands, the United Kingdom (UK), and Spain. The main outcome was first occurrence of myocarditis or pericarditis. RD and IR before COVID-19 disease and after each COVID-19 vaccine dose in those without COVID-19 were calculated. The SCRI calculated IRR with 60-day control period prior to vaccination and 28-day risk windows, with adjustment for seasonality. All analyses were stratified by age (<30 and >= 30 years) and in the cohorts refined age-bands for<30 were utilised. Result(s): The study cohort comprised 35,365,669 persons with median age between 39-49 years, 57.4% received at least one COVID-19 vaccine dose and 77.6% of these received two. Myocarditis background rates were highest in persons 18-29 years (IR 2.8, 95% CI [1.5-4.1] to 6.4 [3.8-9.0] across UK, the Netherlands and Spain, and for 12-17 years in Italy (IR = 9.9 [5.3-14.4]). Pericarditis rates were higher in persons>30 years (standardised IR from 11.6 [10.9-12.4] to 29.7 [19.8-22.1] across databases). RD of myocarditis were significantly elevated after Moderna dose 2 in persons between 18-29 years in Italy. Significantly reduced RD of pericarditis in the age group above 30 years was seen for Pfizer, Moderna and AstraZeneca. The SCRI showed significantly higher myocarditis IRR after dose 1 of Pfizer (IRR = 3.3 [1.2-9.4]), and also after dose 2 of Pfizer and Moderna in persons 12-29 years (IRR of 7.8 [2.6-23.5] and 6.1 [1.1-33.5], respectively). No association was observed between COVID-19 vaccination and pericarditis in the SCRI. In a sensitivity analysis, occasional significant association was seen for AstraZeneca dose 2 and myocarditis. Conclusion(s): Myocarditis is rare, but rates were increased significantly after both doses of Pfizer and the second dose of Moderna vaccines in persons below 30 years of age. This was not seen for pericarditis.
ABSTRACT
Introduction: Some COVID-19 vaccines (Moderna and Pfizer) have been associated with an elevated risk of myocarditis in younger adults. However, observational studies were unable to stratify by dose and had limited ability to evaluate the effect of adenovirus-based COVID-19 vaccines due to the limited distribution of these in their study populations [1-4]. Objective: Estimate the incidence rates (IR), rate differences (RD) and incidence rate ratios (IRR) of myocarditis and pericarditis before and after each dose of mRNA (Pfizer and Moderna) and adenovirusplatform (AstraZeneca and Janssen) COVID-19 vaccines. Methods: We conducted a population-based cohort design with nested self-controlled risk interval (SCRI) study. Participants were followed from 1st January 2020 to 31st December 2021. Data were derived from healthcare data from five population-based data sources in four European countries: Italy, the Netherlands, the United Kingdom (UK), and Spain. The main outcome was first occurrence of myocarditis or pericarditis. RD and IR before COVID-19 disease and after each COVID-19 vaccine dose in those without COVID-19 were calculated. The SCRI calculated IRR with 60-day control period prior to vaccination and 28-day risk windows, with adjustment for seasonality. All analyses were stratified by age (< 30 and > 30 years) and in the cohorts refined age-bands for < 30 were utilised. Results: The study cohort comprised 35,365,669 persons with median age between 39-49 years, 57.4% received at least one COVID-19 vaccine dose and 77.6% of these received two. Myocarditis background rates were highest in persons 18-29 years (IR 2.8, 95% CI [1.5-4.1] to 6.4 [3.8-9.0] across UK, the Netherlands and Spain, and for 12-17 years in Italy (IR = 9.9 [5.3-14.4]). Pericarditis rates were higher in persons > 30 years (standardised IR from 11.6 [10.9-12.4] to 29.7 [19.8-22.1] across databases). RD of myocarditis were significantly elevated after Moderna dose 2 in persons between 18-29 years in Italy. Significantly reduced RD of pericarditis in the age group above 30 years was seen for Pfizer, Moderna and AstraZeneca. The SCRI showed significantly higher myocarditis IRR after dose 1 of Pfizer (IRR = 3.3 [1.2-9.4]), and also after dose 2 of Pfizer and Moderna in persons 12-29 years (IRR of 7.8 [2.6-23.5] and 6.1 [1.1-33.5], respectively). No association was observed between COVID-19 vaccination and pericarditis in the SCRI. In a sensitivity analysis, occasional significant association was seen for AstraZeneca dose 2 and myocarditis. Conclusion: Myocarditis is rare, but rates were increased significantly after both doses of Pfizer and the second dose of Moderna vaccines in persons below 30 years of age. This was not seen for pericarditis.