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

• Published in: JAMA network open 2021-09, Vol.4 (9), p.e2125524-e2125524
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Allergies; Allergy; Anaphylaxis; Coronaviruses; COVID-19 vaccines; COVID-19 Vaccines - adverse effects; COVID-19 Vaccines - therapeutic use; Drug-Related Side Effects and Adverse Reactions - diagnosis; Drug-Related Side Effects and Adverse Reactions - epidemiology; Female; Humans; Hypersensitivity - diagnosis; Hypersensitivity - epidemiology; Male; Middle Aged; mRNA vaccines; Online Only; Original Investigation; Polyethylene glycol; Risk Factors; United States - epidemiology; United States Food and Drug Administration - organization & administration; United States Food and Drug Administration - statistics & numerical data; Vaccination - adverse effects
• ISSN: 2574-3805; 2574-3805
• DOI: 10.1001/jamanetworkopen.2021.25524

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. To characterize the immunologic mechanisms underlying allergic reactions to these vaccines. 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. FDA-authorized mRNA COVID-19 vaccines. 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. 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. 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.