{"doi":"10.1001/jamanetworkopen.2021.25524","title":"Assessment of Allergic and Anaphylactic Reactions to mRNA COVID-19 Vaccines With Confirmatory Testing in a US Regional Health System","abstract":"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.","journal":"JAMA Network Open","year":2021,"id":148070,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":137,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9653,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":631335,"name":"Theo T. Snow","orcid":null,"position":1,"is_corresponding":false},{"id":586081,"name":"Alexandra S. 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Sharon Chinthrajah","orcid":"0000-0003-2467-4256","position":9,"is_corresponding":false},{"id":617332,"name":"Evan Do","orcid":null,"position":10,"is_corresponding":false},{"id":616084,"name":"Iris Chang","orcid":"0009-0007-1971-8513","position":11,"is_corresponding":false},{"id":312706,"name":"Diane Dunham","orcid":null,"position":12,"is_corresponding":false},{"id":225720,"name":"Grace M. Lee","orcid":"0000-0002-0051-2466","position":13,"is_corresponding":false},{"id":431862,"name":"Ruth O’Hara","orcid":"0000-0001-6583-4995","position":14,"is_corresponding":false},{"id":631337,"name":"Helen Park","orcid":null,"position":15,"is_corresponding":false},{"id":465642,"name":"Mohamed H. Shamji","orcid":"0000-0003-3425-3463","position":16,"is_corresponding":false},{"id":277997,"name":"Lisa M. Schilling","orcid":"0000-0002-6878-189X","position":17,"is_corresponding":false},{"id":237674,"name":"Sayantani Sindher","orcid":"0000-0003-0387-2800","position":18,"is_corresponding":false},{"id":631338,"name":"Deepak Sisodiya","orcid":null,"position":19,"is_corresponding":false},{"id":630131,"name":"Eric Smith","orcid":"0000-0002-1262-3112","position":20,"is_corresponding":false},{"id":73045,"name":"Mindy Tsai","orcid":"0000-0002-8421-4721","position":21,"is_corresponding":false},{"id":73046,"name":"Stephen J. Galli","orcid":"0000-0001-5736-5340","position":22,"is_corresponding":false},{"id":281744,"name":"Cezmi A. Akdiş","orcid":"0000-0001-8020-019X","position":23,"is_corresponding":false},{"id":36438,"name":"Kari C. Nadeau","orcid":"0000-0002-2146-2955","position":24,"is_corresponding":false},{"id":241990,"name":"Christopher Warren","orcid":"0000-0002-8924-3329","position":0,"is_corresponding":true}],"reference_count":37,"raw_metadata":null,"created_at":"2026-07-18T23:42:41.063423Z","pmid":"34533570","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}