Genomics and COVID-19 Vaccine Adverse Events

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)

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).

Study Overview

• Status: Recruiting
• Conditions: Vaccine Adverse Reaction
• Intervention / Treatment: Biological: COVID-19 vaccines

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 6325

Contacts and Locations

• Study Contact: Name: Bruce Carleton, PharmD; Phone Number: 1.877.878.4131; Email: bcarleton@popi.ubc.ca

Study Locations

• Canada
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 4H4
      • Recruiting
      • British Columbia Children's Hospital Research Institute
      • Contact: Bruce Carleton, PharmD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Any individual who received a COVID-19 vaccine.

A total of 825 adverse event cases (n=275 each for GBS, VITT/TTS, and myocarditis/pericarditis) and 5,500 vaccine-matched controls (n=2,750 each for mRNA and adenovirus vector COVID-19 vaccine platforms) will be recruited.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Case with COVID-19 vaccine adverse event; Patients with GBS, VITT/TTS, or myocarditis/pericarditis after COVID-19 vaccination	Biological: COVID-19 vaccines; Any licensing COVID-19 vaccine platform
Control without COVID-19 vaccine adverse event; Participants without experiencing GBS, VITT/TTS, or myocarditis/pericarditis after COVID-19 vaccination	Biological: COVID-19 vaccines; Any licensing COVID-19 vaccine platform

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: University of British Columbia
• Collaborators: Centers for Disease Control and Prevention
• Investigators: Principal Investigator: Bruce Carleton, PharmD, University of British Columbia

Publications and helpful links

Helpful Links

• Global Vaccine Data Network and project information

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2022
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: January 25, 2022
• First Submitted That Met QC Criteria: January 25, 2022
• First Posted (Actual): January 28, 2022

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 27, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Genomics; Pericarditis; Myocarditis; COVID-19 vaccine adverse event; Guillain-Barré syndrome (GBS); Vaccine-induced Immune Thrombotic Thrombocytopenia (VITT); Thrombosis with thrombocytopenia syndrome (TTS)
• Additional Relevant MeSH Terms: Post-Infectious Disorders; Nervous System Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Neuromuscular Diseases; Chronic Disease; Disease Attributes; Autoimmune Diseases; Immune System Diseases; Peripheral Nervous System Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Cardiomyopathies; Polyneuropathies; Polyradiculoneuropathy; Pathological Conditions, Signs and Symptoms; Myocarditis; Pericarditis; Guillain-Barre Syndrome; Biological Products; Complex Mixtures; Vaccines; Viral Vaccines; COVID-19 Vaccines
• Other Study ID Numbers: H21-03404

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes