Cohort monitoring of 29 Adverse Events of Special Interest prior to and after COVID-19 vaccination in four large European electronic healthcare data sources
medrxiv(2022)
Abstract
Setting Primary and/or secondary health care data from four European countries: Italy, the Netherlands, the United Kingdom, Spain
Participants Individuals with complete data for the year preceding enrollment or those born at the start of observation time. The cohort comprised 25,720,158 subjects.
Interventions First and second dose of Pfizer, AstraZeneca, Moderna, or Janssen COVID-19 vaccine.
Main outcome measures 29 adverse events of special interest (AESI): acute aseptic arthritis, acute coronary artery disease, acute disseminated encephalomyelitis (ADEM), acute kidney injury, acute liver injury, acute respiratory distress syndrome, anaphylaxis, anosmia or ageusia, arrhythmia, Bells’ palsy, chilblain-like lesions death, erythema multiforme, Guillain Barré Syndrome (GBS), generalized convulsion, haemorrhagic stroke, heart failure, ischemic stroke, meningoencephalitis, microangiopathy, multisystem inflammatory syndrome, myo/pericarditis, myocarditis, narcolepsy, single organ cutaneous vasculitis (SOCV), stress cardiomyopathy, thrombocytopenia, thrombotic thrombocytopenia syndrome (TTS) venous thromboembolism (VTE)
Results 12,117,458 individuals received at least a first dose of COVID-19 vaccine: 54% with Comirnaty (Pfizer), 6% Spikevax (Moderna), 38% Vaxzevria (AstraZeneca) and 2% Janssen Covid-19 vaccine. AESI were very rare <10/100,000 PY in 2020, only thrombotic and cardiac events were uncommon. After adjustment for factors associated with severe COVID, 10 statistically significant associations of pooled incidence rate ratios remained based on dose 1 and 2 combined. These comprised anaphylaxis after AstraZeneca vaccine, TTS after both AstraZeneca and Janssen vaccine, erythema multiforme after Moderna, GBS after Janssen vaccine, SOCV after Janssen vaccine, thrombocytopenia after Janssen and Moderna vaccine and VTE after Moderna and Pfizer vaccines. The pooled rate ratio was more than two-fold increased only for TTS, SOCV and thrombocytopenia.
Conclusion We showed associations with several AESI, which remained after adjustment for factors that determined vaccine roll out. Hypotheses testing studies are required to establish causality.
### Competing Interest Statement
No author has direct financial conflicts of interest. Authors work for organizations who are conducting research for multiple study requesters including the European Medicines Agency and vaccine manufactures. All studies are conducted according to the ENCePP code of conduct for scientific independence
### Clinical Protocols
### Funding Statement
The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network (led by Utrecht University) with collaboration from the Vaccine Monitoring Collaboration for Europe network (). Scientific work for this project was coordinated by the University Medical Center Utrecht. The project has received support from the European Medicines Agency under the Framework service contract nr EMA/2018/28/PE. The pipeline development and quality checks is funded by the IMI-ConcePTION project This document expresses the opinion of the authors of the paper, and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or one of its committees or working parties.
### Author Declarations
I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.
Yes
The details of the IRB/oversight body that provided approval or exemption for the research described are given below:
This study is based on re-use of clinical data that is pseudonomized. This does not require review from IRBs. Each data access provider (PHARMO, ARS, BIFAP, CPRD) has documented clearance from their respective local governance organizations that oversee re-use of available pseudonomized data for the objectives described.
I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.
Yes
I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as [ClinicalTrials.gov][1]. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).
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I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable.
Yes
The protocol for this study is publicly available The full report for this study is publicly available at Zenodo.
[1]: https://ClinicalTrials.gov
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Key words
cohort monitoring,vaccination,adverse events
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