Billions of doses of COVID-19 vaccines have been administered to people across the world, with evidence of good effectiveness and a favourable safety profile. However, rare, and sometimes serious side effects have been reported. It is important to continue to monitor the safety of the COVID-19 vaccines, to support vaccine confidence, to add to available evidence, and to highlight any potential possible reasons for side effects.
This study seeks to evaluate the safety of COVID-19 vaccines, by comparing the frequency of four important side effects. The four conditions to be assessed will be: two forms of inflammation of the heart (Myocarditis and pericarditis), a condition that affects the nervous system (Guillain-Barré Syndrome (GBS)) as well as a new blood clotting condition, known as Vaccine-Induced Thrombosis and Thrombocytopenia (VITT). These four conditions will be compared in vaccinated and unvaccinated individuals. We will investigate possible reasons for the development of myocarditis and pericarditis, GBS, and VITT following COVID-19 vaccination, and will assess the severity of these side effects.
Results of this study will better estimate the risk of myocarditis and pericarditis, GBS, and VITT following COVID-19 vaccination. The results from this study will contribute to a larger European study to allow for larger numbers to be assessed to gain the best possible insight into the reason why these side effects have occurred, that will ultimately improve vaccine safety.
COVID-19 vaccinations have a favourable benefit/risk profile, having been rapidly deployed since 2021. However, further investigation of Adverse Events of Special Interest (AESI), including myocarditis, pericarditis, Guillain-Barré Syndrome (GBS), and Vaccine-Induced Thrombosis and Thrombocytopenia (VITT) is warranted.
This study will use a retrospective self-controlled case series design to examine the association of myocarditis and pericarditis, GBS, and VITT with COVID-19 vaccines, comparing the incidence risk of these AESI following COVID-19 vaccination with a control period of no COVID-19 vaccine exposure. The retrospective self-controlled risk interval design will identify risk and control windows surrounding the point of exposure (vaccination), to ensure all cases share the same risk and control periods. Fixed effects Poisson regression will be utilised to evaluate relative incidences for all cases as well as subset analysis by age and sex. To determine the influence of vaccine interval the Pearson correlation coefficient will be determined. Risk factors for myocarditis, pericarditis, GBS, and VITT will be investigated. Clinical characteristics, severity, and prognosis of these events following COVID-19 vaccination will also be examined.
Using CPRD, we will define a cohort of eligible patients who have a recorded code for one of the four AESI included (prior to or following COVID-19 vaccination). Self-controlled risk interval methodology will be utilised to determine whether there is an increased risk of myocarditis, pericarditis, GBS, or VITT following COVID-19 vaccine exposure. Each case will act as their own control, contributing both exposed and unexposed time periods. The results from this CPRD self-controlled case series will be pooled with data from other European sites, to contribute to a wider network study. Results from all sites will be meta-analysed to produce an overall measure of association for each of the four included AESI.
Results of this study will inform vaccine policymakers, immunisation providers, and vaccinees.
The primary outcomes for each sub-study are as follows:
• Myocarditis and pericarditis,
• Guillain-Barre Syndrome,
• Vaccine-induced Thrombosis with Thrombocytopenia, Thrombosis with Thrombocytopenia Syndrome. To be considered a possible case, an individual would have to have at least one code for thrombocytopenia and one for thrombosis in the same hospitalisation or health encounter.
Please find code lists for each in Appendices 1-4.
Debabrata Roy - Chief Investigator - Drug Safety Research Unit
Alison Yeomans - Corresponding Applicant - Drug Safety Research Unit
Catherine Fry - Collaborator - Drug Safety Research Unit
Denise Morris - Collaborator - Drug Safety Research Unit
Kathryn Morton - Collaborator - Drug Safety Research Unit
Saad Shakir - Collaborator - Drug Safety Research Unit
Samantha Lane - Collaborator - Drug Safety Research Unit
Taylor Aurelius - Collaborator - Drug Safety Research Unit
CPRD Aurum Ethnicity Record;CPRD Aurum Pregnancy Register