Genomics and COVID-19 Vaccine Adverse Events

Study Overview
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Brief Summary
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Vaccines routinely used are extremely safe; however, severe adverse events to vaccines do occur. As vaccination against COVID-19 has begun, adverse events to the vaccine, particularly Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis, after COVID-19 vaccination have been reported worldwide. Study hypothesis: there are genetic factors that contribute to increased risks of particular COVID-19 vaccine-induced adverse events. The objective of the study is to determine if there are specific genetic factors strongly associated with each of the COVID-19 vaccine-induced adverse events (i.e., GBS, VITT/TTS, and myocarditis/pericarditis).

Detailed Description
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Purpose: Reduce the risk of COVID-19 vaccine-induced adverse events (i.e., GBS, VITT/TTS, and myocarditis/pericarditis) through improved understanding of the biology underlying these severe adverse events and the genetic contribution to their cause Research Design: Prospective case-control study designs will be performed to investigate the genetic associations of Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis strongly associated (OR ≥ 3.0) with COVID-19 vaccination. Determined cases of specific COVID-19 vaccine-induced GBS, VITT/TTS, and myocarditis/pericarditis, and vaccinated controls without these adverse events will be included. Saliva DNA samples from eligible adverse event cases and vaccinated controls will be collected. Candidate gene and genome-wide association studies (GWAS) approaches will be conducted. Genomics analyses will be stratified by severity, age, sex, vaccine, and other critical covariates as determined by the GVDN Work Group for each adverse event and as adequately powered analyses allow. To complement GWAS, particularly in protein-coding regions, additional whole-exome sequencing (WES) will be performed on the most severe patients who are categorized as Brighton Collaboration Level One case of COVID-19 vaccine-induced adverse events to identify the most possible disease-causing mutations.

Official Title
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Genomics of COVID-19 Vaccine-induced Adverse Events (Guillain-Barré Syndrome [GBS], Vaccine-induced Immune Thrombotic Thrombocytopenia [VITT]/Thrombosis With Thrombocytopenia Syndrome [TTS], and Myocarditis/Pericarditis)

Conditions
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Vaccine Adverse Reaction

Intervention / Treatment
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* Biological: COVID-19 vaccines


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Case: Any patient who received COVID-19 vaccines and developed GBS, VITT/TTS, or myocarditis/pericarditis after vaccination Control: Any participant who received COVID-19 vaccines and does not experience GBS, VITT/TTS, or myocarditis/pericarditis. Exclusion Criteria: Individuals who have not received a COVID-19 vaccine Individuals who are unable to provide informed consent

Ages Eligible for Study
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Minimum Age: 5 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Case with COVID-19 vaccine adverse event<br>Patients with GBS, VITT/TTS, or myocarditis/pericarditis after COVID-19 vaccination | Biological: COVID-19 vaccines<br>* Any licensing COVID-19 vaccine platform<br>|
| Control without COVID-19 vaccine adverse event<br>Participants without experiencing GBS, VITT/TTS, or myocarditis/pericarditis after COVID-19 vaccination | Biological: COVID-19 vaccines<br>* Any licensing COVID-19 vaccine platform<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine specific genetic factors associated with particular COVID-19 vaccine-induced Guillain-Barré syndrome (GBS), vaccine-induced immune thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS), and myocarditis/pericarditis |  | December 2025 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Genomics, COVID-19 vaccine adverse event, Guillain-Barré syndrome (GBS), Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT), Thrombosis with thrombocytopenia syndrome (TTS), Myocarditis, Pericarditis