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The conundrum of COVID-19 mRNA vaccine-induced anaphylaxis
Muhammad Bilal Khalid1, Pamela A Frischmeyer-Guerrerio1
1Laboratory of Allergic Diseases, Food Allergy Research Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Md.
Abstract:
Novel messenger RNA (mRNA) vaccines have proven to be effective tools against coronavirus disease 2019, and they have changed the course of the pandemic. However, early reports of mRNA vaccine-induced anaphylaxis resulted in public alarm, contributing toward vaccine hesitancy. Although initial reports were concerning for an unusually high rate of anaphylaxis to the mRNA vaccines, the true incidence is likely comparable with other vaccines. These reactions occurred predominantly in young to middle-aged females, and many had a history of allergies. Although initially thought to be triggered by polyethylene glycol (PEG), lack of reproducibility of these reactions with subsequent dosing and absent PEG sensitization point away from an IgE-mediated PEG allergy in most. PEG skin testing has poor posttest probability and should be reserved for evaluating non-vaccine-related PEG allergy without influencing decisions for subsequent mRNA vaccination. Immunization stress-related response can closely mimic vaccine-induced anaphylaxis and warrants consideration as a potential etiology. Current evidence suggests that many individuals who developed anaphylaxis to the first dose of an mRNA vaccine can likely receive a subsequent dose after careful evaluation. The need to understand these reactions mechanistically remains critical because the mRNA platform is rapidly finding its way into other vaccinations and therapeutics.
Insights
Messenger RNA (mRNA) vaccines are effective, but anaphylaxis reports caused hesitancy. Most reactions were mild, not IgE-mediated PEG allergy, and many can receive subsequent doses.
Area of Science:
- Immunology
- Vaccinology
- Allergology
Background:
- Novel messenger RNA (mRNA) vaccines significantly impacted the coronavirus disease 2019 pandemic.
- Early reports of anaphylaxis following mRNA vaccination raised public concern and vaccine hesitancy.
- Anaphylactic reactions to mRNA vaccines, while initially alarming, appear to occur at an incidence comparable to other vaccines.
Purpose of the Study:
- To investigate the incidence and potential causes of anaphylaxis after mRNA vaccination.
- To differentiate true vaccine-induced anaphylaxis from other conditions like immunization stress-related responses.
- To guide clinical decisions regarding subsequent mRNA vaccine doses for individuals who experienced anaphylaxis.
Main Methods:
- Review of early reports and clinical data on mRNA vaccine-associated anaphylaxis.
- Analysis of patient demographics, allergy history, and reaction characteristics.
- Evaluation of the role of polyethylene glycol (PEG) and PEG skin testing.
- Consideration of immunization stress-related responses as a differential diagnosis.
Main Results:
- Anaphylaxis predominantly affected young to middle-aged females, often with a history of allergies.
- Reactions were frequently not reproducible with subsequent doses, and PEG sensitization was often absent, suggesting non-IgE-mediated mechanisms.
- Immunization stress-related responses can mimic anaphylaxis.
- Many individuals experiencing anaphylaxis with the first dose can likely receive subsequent doses after careful evaluation.
Conclusions:
- The true incidence of mRNA vaccine-induced anaphylaxis is likely comparable to other vaccines.
- Polyethylene glycol (PEG) is unlikely the primary allergen in most cases of mRNA vaccine-induced anaphylaxis.
- Immunization stress-related responses should be considered in the differential diagnosis.
- Careful evaluation allows many individuals to receive subsequent mRNA vaccine doses, but further mechanistic understanding is crucial for the expanding mRNA platform.
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