Assessing Safety of Coronavirus Infection (COVID-19) Messenger RNA (mRNA) Vaccine Administration in the Setting of a Previous Adverse Reaction

March 6, 2026 updated by: James Baker Jr MD, University of Michigan

Assessing Safety of COVID-19 mRNA Vaccine Administration in the Setting of a Previous Adverse Reaction

This study will evaluate the safety of administering an additional dose of an mRNA COVID-19 vaccine or mRNA bivalent COVID-19 booster vaccine to individuals who have had adverse reactions to a previous dose or administering an initial dose of an mRNA COVID-19 vaccine to individuals with a personal history of allergic reaction. In addition, this study will evaluate the safety of administering an initial or additional dose or bivalent booster of an mRNA COVID-19 vaccine to individuals experiencing an adverse reaction to a natural COVID-19 infection ("long COVID").

Eligible participants enrolled in this trial will receive an initial or additional dose of either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna COVID-19 bivalent vaccine. Participants will also be required to have 1-2 in person visits along with phone call follow up visits.

We hypothesize that individuals who have had adverse reactions to a previous dose of an mRNA COVID-19 vaccine will tolerate an additional dose of the primary mRNA vaccine or bivalent booster, as indicated, and those with a personal history of allergic reaction will tolerate an initial dose of an mRNA COVID-19 vaccine. We also hypothesize that those individuals experiencing an adverse reaction will tolerate an initial or additional dose of a primary mRNA COVID-19 bivalent vaccine, as indicated.

The study hypothesizes that individuals that have had adverse reactions to a dose of an mRNA COVID-19 vaccine will tolerate an additional dose and those with a personal history of allergic reaction will tolerate vaccination with an mRNA COVID-19 vaccine.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

137

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Michigan
      • Ann Arbor, Michigan, United States, 48109
        • University of Michigan

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. Age over 18.
  2. Participant must be able to understand and provide informed consent
  3. No evidence of infectious illness (defined as fever >38⁰C, vomiting, diarrhea, new cough, new shortness of breath, new congestion, new runny nose, new headache or sore throat) within 14 days of vaccine administration.
  4. Subjects must have a history of adverse reaction to either the Pfizer-BioNTech mRNA COVID vaccination or the Moderna mRNA COVID vaccination, a personal history of allergic reaction without prior mRNA COVID vaccination, or a history of adverse reaction to natural COVID infection.
  5. Females of childbearing potential must have a negative pregnancy test prior to vaccination.

Exclusion Criteria

  1. Under age 18
  2. Inability or unwillingness of a participant to give written informed consent
  3. Evidence of COVID-19 infection within 21 days of vaccination visit
  4. History of antibody agent or convalescent plasma for treatment or prevention of COVID-19 within 90 days
  5. Individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of the Pfizer-BioNTech mRNA COVID-19 vaccination or the Moderna mRNA COVID-19 vaccination.

  6. History of underlying immune disorder.

    • Pregnancy

    • Immunocompromised

      • Persons with primary or acquired immunodeficiency
      • Persons on anti-rejection therapy following solid organ transplant or bone marrow transplant
      • Persons on biologic therapeutic agents
      • Persons with malignancy and ongoing or recent chemotherapy
      • Persons receiving systemic immunosuppressive therapy, including corticosteroids equivalent to 20 mg/day of prednisone for 2 weeks
    • Persons with chronic kidney disease stage 3 or higher
    • Persons with history of significant pulmonary compromise

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Pfizer-BioNTech mRNA COVID-19 vaccine
Subject will receive an initial or additional dose of the Pfizer-BioNTech (Comirnaty) mRNA COVID-19 vaccine
Biological: Pfizer-BioNTech mRNA COVID-19 vaccine
Participants will receive an initial or additional dose of a highly protective COVID-19 mRNA vaccine for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in an environment where the investigators and staff are experienced in the care of patients with allergic reactions.
Other Names:
  • Comirnaty
Experimental: Moderna mRNA COVID-19 vaccine
Subject will receive an initial or additional dose of the Moderna mRNA COVID-19 vaccine
Biological: Moderna mRNA COVID-19 vaccine
Participants will receive an initial or additional dose of a highly protective COVID-19 mRNA vaccine for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus in an environment where the investigators and staff are experienced in the care of patients with allergic reactions.
Other Names:
  • Spikevax

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Participants Who Had a Reaction to an Initial or Additional Dose of the Pfizer-BioNTech or Moderna COVID-19 mRNA Vaccine, or Who Had Long COVID
Time Frame: up to approximately 7 days after the vaccine is given

Results reflect the number of participants who had previously received the Pfizer-BioNTech, the Moderna mRNA COVID-19 vaccine, or both, and who had experienced an adverse reaction (AR). An AR would be any symptom reported or objective finding during the 30-minute observation, or any symptom reported at the 7 day follow up. ARs were graded using the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, which utilized the following grades:

Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life-threatening Grade 5 = Death
up to approximately 7 days after the vaccine is given
Number of Participants With Treatment-related Allergic Reaction Adverse Events
Time Frame: up to approximately 7 days after the vaccine is given
The safety of administering an initial or additional dose will be determined by using the grading of systemic allergic reactions will be based on a scale of 1 (mild reaction) to 5 (severe reaction, including death) according to criteria set forth in the Consortium of Food Allergy Research (CoFAR) grading scale (version 3.0) modified for adults as well as the Brighton Collaboration to grade the diagnostic certainty of anaphylaxis. Results reflect the number of participants who received an initial dose or were revaccinated during the trial, and experienced related acute allergic reaction adverse event, and what the CoFAR severity for the events was. Events were deemed to be allergic if symptoms were consistent with an IgE-reaction and symptom onset began within 1 hour of vaccination.
up to approximately 7 days after the vaccine is given

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of Non-allergic Clinical Adverse Reactions
Time Frame: up to approximately 7 days after the vaccine is given
Results reflect the number of participants who experienced a non-allergic clinical adverse reaction (AR). A non-allergic clinical AR was determined by non-allergic symptomatology and time frame from when the participant received a vaccine. Nonallergic ARs were symptoms that were inconsistent with an IgE-mechanism or had an onset greater than 1 hour following vaccination. ARs were graded using the FDA Guidance for Industry Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, which utilized the following grades: Grade 1 = Mild Grade 2 = Moderate Grade 3 = Severe Grade 4 = Life-threatening Grade 5 = Death
up to approximately 7 days after the vaccine is given

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Michigan

Collaborators

The Wallace Foundation

Investigators

  • Principal Investigator: James Baker, MD, University of Michigan

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 21, 2022

Primary Completion (Actual)

March 7, 2025

Study Completion (Actual)

March 7, 2025

Study Registration Dates

First Submitted

January 26, 2022

First Submitted That Met QC Criteria

January 26, 2022

First Posted (Actual)

January 28, 2022

Study Record Updates

Last Update Posted (Actual)

March 27, 2026

Last Update Submitted That Met QC Criteria

March 6, 2026

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HUM00206480

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

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.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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