Cohort monitoring of Adverse Events of Special Interest and COVID-19 diagnoses prior to and after COVID-19 vaccination

Date of Approval
Application Number
Technical Summary

The global rapid spread of COVID-19 caused by the SARS-CoV2 triggered the need for developing vaccines to control for this pandemic. This study will generate incidence rates of adverse events of special interest (AESI) prior to and after COVID-19 vaccination, to facilitate monitoring of the benefit-risk profile of licensed COVID-19 vaccines.

The objectives of this study are to monitor and estimate the incidence rates of adverse events of special interest (AESI), diagnosed COVID-19 in vaccinated and non-vaccinated persons by data source over the period January 1st 2020-October 31st 2021 by brand and dose of vaccine and age of the population. We will further stratify by the at-risk population for developing severe COVID-19 by data source, brand and dose of vaccine as well as age.

Study design:
A retrospective, multi-database, dynamic cohort study in 4 data sources in 4 European countries (Italy, Netherlands, Spain, United Kingdom).

Variables of interest will be:
• Person-time: birth and death dates as well as periods of observation.
• Events: dates of medical and/or procedure and/or prescription/dispensing codes to identify AESI, COVID-19 and at-risk medical conditions.
• Vaccines: vaccine brands and batch numbers (where possible)

Data analysis:
Incidence rates of listed AESI will be calculated in non-exposed time periods (prior to vaccination or in non-vaccinated) and during each one-week risk window since vaccination by each dose, stratified per brand of vaccine. Data on vaccine exposures (doses), incidence rate of diagnosed COVID-19 and each AESI of interest by time since vaccination dose will be displayed on a dashboard. Incidence rates (and 95%CI) of COVID-19 and AESI among at-risk populations (in terms of comorbidity and by age) will also be computed.

Health Outcomes to be Measured

COVID disease; Multisystem inflammatory syndrome; Acute respiratory distress syndrome;Acute cardiovascular injury (including microangiopathy, heart failure, stress cardiomyopathy, coronary artery disease, arrhythmia, myocarditis); Coagulation disorders ( including deep vein thrombosis, pulmonary embolus, cerebrovascular stroke, haemorrhagic disease, cerebral vein sinus
thrombosis, disseminated intravascular coagulation); Generalised convulsion ; Guillain Barré Syndrome; Diabetes (type 1); Acute kidney injury; Acute liver injury; Anosmia, ageusia ; Chilblain-like lesions; Single organ cutaneous vasculitis ;Erythema multiforme
Anaphylaxis; Death (any cause) ;Sudden death (by codes) ;Acute aseptic arthritis ;Meningoencephalitis ;Acute disseminated encephalomyelitis (ADEM);Narcolepsy ;Thrombocytopenia;Transverse myelitis;Bells’ palsy


Olaf Klungel - Chief Investigator - Utrecht University
Patrick Souverein - Corresponding Applicant - Utrecht University


HES Admitted Patient Care