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Immunization Stress-Related Response Mimics Vaccine-induced Anaphylaxis to COVID-19 Vaccines

AAAAI News Release

February 3, 2023

April Presnell, Media & Member Communications Manager
(414) 272-6071

This mimic likely contributes to the reported 'allergic' reactions following COVID-19 mRNA vaccination, according to a study to be presented at the 2023 AAAAI Annual Meeting.

Milwaukee, WI - COVID-19 mRNA Vaccine-induced Immunization Stress-Related Response (ISRR) mimics many symptoms of anaphylaxis, which is likely one of the explanations for higher reports of allergic reactions during COVID-19 vaccination. These findings are being presented at the 2023 Annual Meeting of the American Academy of Allergy, Asthma & Immunology (AAAAI) by Muhammad B. Khalid, MD, who led the research with Dr. Pamela A. Frischmeyer-Guerrerio, MD, PhD.  Dr. Khalid is a clinical fellow in the Laboratory of Allergic Diseases of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health. Dr. Guerrerio is the principal investigator for this research and chief of the NIAID Laboratory of Allergic Diseases.

COVID-19 mRNA vaccine anaphylaxis has been reported at higher rates than conventional vaccine anaphylactic reactions. Dr. Khalid and colleagues examined the safety of additional COVID-19 vaccinations in patients who experienced a systemic allergic reaction after their first dose. NIAID sponsored and funded the clinical trial, which took place under carefully controlled conditions at the NIH Clinical Center in Bethesda, Maryland.

For the study, 16 patients who reported a systemic allergic reaction after their first Pfizer-BioNTech or Moderna COVID-19 vaccine dose were randomized to receive either a second dose of the Pfizer-BioNTech vaccine followed by a placebo shot the next day or a placebo shot followed by a second dose of the Pfizer-BioNTech vaccine the next day. Additionally, 13 of these participants received an unblinded Pfizer-BioNTech booster dose and had skin testing performed.

Nine patients developed immediate non-allergic symptoms after receiving the second dose of the Pfizer-BioNTech vaccine and 11 participants developed immediate non-allergic symptoms following placebo, with a median onset of three minutes following administration. Symptoms included numbness, tingling, dizziness, throat tightness, dysphagia, and transient hypertension, all of which are consistent with ISRR. Of these reactions, 45% were considered moderate to severe. Only three patients developed a recurrent allergic reaction after receiving the Pfizer-BioNTech vaccine, with a median onset of four minutes after vaccination. No participants who received the placebo subsequently developed an allergic reaction.

After completing the unblinded booster, 10 out of 13 patients experienced ISRR symptoms and one patient had a recurrent allergic reaction. Two individuals in the study tested positive with Pfizer-BioNTech vaccine intradermal testing, and all undergoing excipient skin testing had negative results.

While anaphylaxis can rarely occur following COVID-19 vaccination, ISRR is a highly under-recognized mimic, Dr. Khalid and colleagues report. Due to the similarity of ISRR symptoms to those of anaphylaxis, the rate of true anaphylaxis following COVID-19 vaccination is likely lower than estimated, based on the study findings. It is important that healthcare professionals are able to recognize ISRR so they can properly distinguish it from anaphylaxis following vaccination.

Visit to learn more about COVID-19. Research presented at the AAAAI Annual Meeting, February 24-27 in San Antonio, Texas, is published in an online supplement to The Journal of Allergy and Clinical Immunology.

The American Academy of Allergy, Asthma & Immunology (AAAAI) is the leading membership organization of more than 7,100 allergists, asthma specialists, clinical immunologists, allied health professionals and others with a special interest in the research and treatment of allergic and immunologic diseases. The AAAAI is the go-to resource for patients living with allergies, asthma and immune deficiency disorders. Established in 1943, the AAAAI has more than 7,100 members in the United States, Canada and 72 other countries. The AAAAI’s Find an Allergist/Immunologist service is a trusted resource to help you find a specialist close to home.