Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System

Warren, Christopher Michael; Snow, Theo Thomas; Lee, Alexandra S.; Shah, Mihir Mukesh; Heider, Anja; Blomkalns, Andra; Betts, Brooke; Buzzanco, Anthony S.; Gonzalez, Joseph; Chinthrajah, R. Sharon; Do, Evan; Chang, Iris; Dunham, Diane; Lee, Grace; O’Hara, Ruth; Park, Helen; Shamji, Mohamed H.; Schilling, Lisa; Sindher, Sayantani B.; Sisodiya, Deepak; Smith, Eric; Tsai, Mindy; Galli, Stephen J.; Akdis, Cezmi; Nadeau, Kari C.

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.