Related Experiment Video
Updated: Oct 19, 2025
Dynamic Monitoring of Seroconversion using a Multianalyte Immunobead Assay for Covid-19
Published on: February 16, 2022
Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US
Christopher Michael Warren1,2, Theo Thomas Snow1, Alexandra S Lee1
1Sean N. Parker Center for Allergy and Asthma Research at Stanford University, Stanford, California.
Importance:
As of May 2021, more than 32 million cases of COVID-19 have been confirmed in the United States, resulting in more than 615 000 deaths. Anaphylactic reactions associated with the Food and Drug Administration (FDA)-authorized mRNA COVID-19 vaccines have been reported.
Objective:
To characterize the immunologic mechanisms underlying allergic reactions to these vaccines.
Design, Setting, And Participants:
This case series included 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines between December 18, 2020, and January 27, 2021, at a large regional health care network. Participants were individuals who received at least 1 of the following International Statistical Classification of Diseases and Related Health Problems, Tenth Revision anaphylaxis codes: T78.2XXA, T80.52XA, T78.2XXD, or E949.9, with documentation of COVID-19 vaccination. Suspected allergy cases were identified and invited for follow-up allergy testing.
Exposures:
FDA-authorized mRNA COVID-19 vaccines.
Main Outcomes And Measures:
Allergic reactions were graded using standard definitions, including Brighton criteria. Skin prick testing was conducted to polyethylene glycol (PEG) and polysorbate 80 (P80). Histamine (1 mg/mL) and filtered saline (negative control) were used for internal validation. Basophil activation testing after stimulation for 30 minutes at 37 °C was also conducted. Concentrations of immunoglobulin (Ig) G and IgE antibodies to PEG were obtained to determine possible mechanisms.
Results:
Of 22 patients (20 [91%] women; mean [SD] age, 40.9 [10.3] years; 15 [68%] with clinical allergy history), 17 (77%) met Brighton anaphylaxis criteria. All reactions fully resolved. Of patients who underwent skin prick tests, 0 of 11 tested positive to PEG, 0 of 11 tested positive to P80, and 1 of 10 (10%) tested positive to the same brand of mRNA vaccine used to vaccinate that individual. Among these same participants, 10 of 11 (91%) had positive basophil activation test results to PEG and 11 of 11 (100%) had positive basophil activation test results to their administered mRNA vaccine. No PEG IgE was detected; instead, PEG IgG was found in tested individuals who had an allergy to the vaccine.
Conclusions And Relevance:
Based on this case series, women and those with a history of allergic reactions appear at have an elevated risk of mRNA vaccine allergy. Immunological testing suggests non-IgE-mediated immune responses to PEG may be responsible in most individuals.
Insights
Allergic reactions to mRNA COVID-19 vaccines are rare but can occur, particularly in women with a history of allergies. Immunological testing suggests polyethylene glycol (PEG) may trigger non-IgE-mediated responses.
Area of Science:
- Immunology
- Vaccinology
- Allergy and Immunology
Background:
- Millions vaccinated against COVID-19, with rare anaphylactic reactions reported for mRNA vaccines.
- Understanding the immunological mechanisms behind these vaccine allergies is crucial for public health.
Purpose of the Study:
- To investigate the immunological basis of allergic reactions following mRNA COVID-19 vaccination.
- To identify potential triggers and immune pathways involved in vaccine-induced anaphylaxis.
Main Methods:
- A case series of 22 patients with suspected allergic reactions to mRNA COVID-19 vaccines.
- Allergy testing included skin prick tests for polyethylene glycol (PEG) and polysorbate 80 (P80), and basophil activation tests.
- Quantification of immunoglobulin (Ig) G and IgE antibodies to PEG was performed.
Main Results:
- 17 out of 22 patients (77%) met Brighton anaphylaxis criteria; all reactions resolved.
- Skin prick tests showed no reactions to PEG or P80, but one patient reacted to their specific mRNA vaccine.
- Basophil activation tests were positive for PEG in 91% and for the mRNA vaccine in 100% of tested patients.
- No PEG IgE was detected; instead, PEG IgG was found in allergic individuals.
Conclusions:
- Women and individuals with a history of allergies may have a higher risk of mRNA vaccine allergy.
- Findings suggest non-immunoglobulin E (IgE)-mediated immune responses to PEG are likely responsible for most vaccine allergies.
Related Concept Videos
02:06Allergic Reactions
00:42Cross-reactivity
01:27Allergic Drug Reactions