key: cord-1005276-ny0rsv30
authors: Jiang, Shirley Y.; Smith, Eric M.; Vo, Victor; Akdis, Cezmi; Nadeau, Kari C.
title: Non-IgE mediated allergy associated with Pfizer-BioNTech COVID-19 vaccine excipient polyethylene glycol
date: 2021-09-20
journal: Ann Allergy Asthma Immunol
DOI: 10.1016/j.anai.2021.09.012
sha: 5ef886a57cb562f6d9a561001fc374b596b1e943
doc_id: 1005276
cord_uid: ny0rsv30

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Approximately five minutes following administration, she felt dizzy, lightheaded, dyspneic, throat tightening and abdominal pain. Initial blood pressure was 145/94 mmHg and a repeat reading minutes later was 70/42 mmHg with a pulse rate of 150 beats/minute. Her physical exam was significant for faint end-expiratory wheezes. Her systolic blood pressure fell further down to the 50's and a Code Blue was called for additional resources. Intramuscular (IM) epinephrine was administered immediately upon Code Blue team arrival, and two minutes later, her blood pressure recovered to 176/77 mmHg. While her symptoms transiently improved, she continued to have "waves" of chest tightness and dyspnea requiring two subsequent doses of 0.3 mg of IM epinephrine followed by a 20-mcg bolus of epinephrine intravenously and the initiation of an epinephrine infusion at 0.1 µg/kg/min. She additionally received lactated ringer's solution, racemic epinephrine and albuterol nebulizer, famotidine, diphenhydramine, and solumedrol, and was admitted to the ICU. In the ICU, her vital signs improved, and she was weaned off of the epinephrine infusion three hours later. She did not require supplemental oxygen and her wheezing resolved. A tryptase collected approximately 90 minutes following the index event was 6 ng/mL (reference range <11.5 ng/mL). There were no further objective signs of biphasic or protracted anaphylactic reaction, and ultimately, she was discharged from the hospital 5 days later with epinephrine injector pens. The patient was instructed not to receive the second dose of the Pfizer-BioNTech vaccine and was enrolled in the national vaccine adverse event reporting system (VAERS). Allergy testing was pursued on a follow-up clinic visit 21 days later.

The patient received skin prick testing (SPT) to undiluted BNT162b2 vaccine, polyethylene glycol (PEG), which is a small lipophilic excipient in both Pfizer-BioNTech and Moderna vaccines, and polysorbate 80, a known cross-reactant to PEG. Histamine and normal saline were used as positive and negative controls respectively.

Whole blood was obtained from the patient, and activation markers, which are upregulated on basophils during a hypersensitivity reaction, were measured in vitro using flow cytometry. Blood was heparinized, Case reports of suggested IgE-mediated hypersensitivity to PEG provide some insights; however, PEGspecific IgE are often not detectable, which may in some circumstances result from a lack of assay sensitivity [4] [5] [6] [7] . In other cases, PEGylated lipid nanoparticles may activate host immune defense through non-IgE pathways such as Mas-related G protein-coupled receptor X2 (MRGPRX2) mediated direct mast cell and basophil degranulation and complement activation-related pseudoallergy to PEG 8, 9 .

Recent data demonstrates tolerability of a second dose COVID-19 mRNA vaccine with antihistamine or steroid premedication in those with convincing immediate hypersensitivity reactions to the first dose 10 , This suggests a role for possible second or booster dose of mRNA vaccine or alternative Janssen COVID-19 vaccine under allergist supervision for those with vaccine-associated PEG hypersensitivity.

Assessing basophil activation by using flow cytometry and mass cytometry in blood stored 24 hours before analysis

Polyethylene glycol (PEG) is a cause of anaphylaxis to the Pfizer/BioNTech mRNA COVID-19 vaccine

Immediate Hypersensitivity to Polyethylene Glycols and Polysorbates: More Common Than We Have Recognized

Immediate-type hypersensitivity to polyethylene glycols: a review

Polyethylene glycol as a cause of anaphylaxis

Anaphylaxis due to macrogol in a laxative solution with a positive basophil activation test

Anti-PEG IgE in anaphylaxis associated with polyethylene glycol

Potential mechanisms of anaphylaxis to COVID-19 mRNA vaccines

Allergenic components of the mRNA-1273 vaccine for COVID-19: Possible involvement of polyethylene glycol and IgG-mediated complement activation

First-Dose mRNA COVID-19 Vaccine Allergic Reactions: Limited Role for Excipient Skin Testing

We would like to thank Theo Snow, Mihir Shah, and Anja Heider for assistance gathering data and conducting experiments. We would like to thank Vanitha Sampath for manuscript editing.