Allergic reactions to coronavirus disease 2019 vaccines and addressing vaccine hesitancy: Northwell Health experience.

Allergic and nonallergic adverse reactions have been reported with global coronavirus disease 2019 (COVID-19) vaccination. It was previously hypothesized that polyethylene glycol (PEG) may be responsible for anaphylactic reactions to messenger RNA (mRNA) COVID-19 vaccines. To report the workflow established at our institution, types, and frequency of adverse reactions to mRNA COVID-19 vaccines in patients presenting for allergy evaluation. A COVID-19 vaccine adverse reaction registry was established. We used PEG prick skin testing, followed by PEG challenges in selected cases, to ensure PEG tolerance and encourage completion of COVID-19 vaccination series. A total of 113 patients were included. Most vaccine reactions (86.7%) occurred in women. Anaphylaxis occurred only in women, all of which had a history of allergic disease and two-thirds had asthma. Anaphylaxis rate was 40.6 cases per million. None of the anaphylactic cases developed hypotension, required intubation, or required hospital admission. Systemic allergic symptoms, not fulfilling anaphylaxis criteria, were significantly more common in Pfizer-BioNTech than Moderna-vaccinated patients (P = .02). We observed a higher incidence of dermatologic nonurticarial reactions in men (P = .004). Among first-dose reactors, 86.7% received and tolerated the second dose. We observed a high rate of false-positive intradermal skin test results and frequent subjective symptoms with oral PEG challenge. Intradermal PEG testing has limited utility in evaluating anaphylaxis to mRNA vaccines. Most severe postvaccination allergic symptoms are not caused by hypersensitivity to PEG. Most people with reaction to the initial mRNA vaccine can be safely revaccinated. Patients with anaphylaxis to COVID-19 vaccines benefit from physician-observed vaccination.

Kaplan B ，Farzan S ，Coscia G ，Rosenthal DW ，McInerney A ，Jongco AM ，Ponda P ，Bonagura VR ... -  《-》

Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms. Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status. All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats. Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.

Zhou ZH ，Cortese MM ，Fang JL ，Wood R ，Hummell DS ，Risma KA ，Norton AE ，KuKuruga M ，Kirshner S ，Rabin RL ，Agarabi C ，Staat MA ，Halasa N ，Ware RE ，Stahl A ，McMahon M ，Browning P ，Maniatis P ，Bolcen S ，Edwards KM ，Su JR ，Dharmarajan S ，Forshee R ，Broder KR ，Anderson S ，Kozlowski S ... -  《-》

Anaphylaxis associated with the mRNA COVID-19 vaccines: Approach to allergy investigation.

Reports about cases of anaphylaxis to mRNA vaccines have created anxiety in the community and could increase vaccine hesitancy in the population. There are no standardized protocols for allergy testing to mRNA vaccines. PEG is currently the only excipient in both vaccines with recognized allergenic potential. Allergy to PEG has been reported with increasing frequency over recent years, often in patients who had repeated systemic allergic reactions/anaphylaxis to several classes of drugs before diagnosis. Proposed protocols are based on current knowledge about potential mechanisms of anaphylaxis associated with the mRNA vaccines, and the assumption that polyethylene glycol (PEG) is the most likely culprit. Allergy testing to PEGs and mRNA vaccines is complex and carries the risk of anaphylaxis and should be conducted in a specialist drug allergy center. Appropriate PEG-free emergency medical treatment and supervision should be readily available.

Erdeljic Turk V 《-》

Coronavirus disease 2019 vaccine administration in patients with reported reactions to polyethylene glycol- and polysorbate-containing therapeutics.

Polyethylene glycol (PEG) and polysorbate reactions were initially implicated as a likely risk factor for reacting to coronavirus disease 2019 (COVID-19) vaccines and remain a source of vaccine hesitancy despite increasing evidence that they do not pose an increased risk for COVID-19 vaccine reactions. To investigate COVID-19 vaccine safety outcomes in patients with reported reactions to PEG- and polysorbate-containing medications and vaccines. COVID-19 vaccine safety was reviewed in patients with PEG or polysorbate reactions documented in their electronic medical records at a tertiary academic medical center (cohort 1) and patients referred to Allergy and Immunology with reported PEG or polysorbate reactions (cohort 2). COVID-19 vaccine safety was also reviewed following reported symptoms (onset ≤ 12 hours) to first-dose PEG-containing messenger RNA (mRNA) COVID-19 vaccine (cohort 3). Of 252 patients in cohort 1 (n = 202) and cohort 2 (n = 50), 236 (94%) received mRNA COVID-19 vaccines (106 Pfizer, 130 Moderna); 235 received both doses. Only 3 patients from cohort 2 developed mild rash following vaccination. None of the 44 patients in cohort 3 with acute symptoms following first-dose mRNA COVID-19 vaccine (27 Pfizer, 17 Moderna) had previously reported PEG or polysorbate reactions. Of these 44 patients, 43 received the second dose and all 3 who developed symptoms following the second dose (1 required epinephrine) had negative PEG skin testing. Patients with reported reactions to PEG and polysorbate safely received COVID-19 vaccines. PEG and polysorbate skin testing did not identify patients at risk for first dose or recurrent reactions to COVID-19 vaccines. Screening for PEG and polysorbate allergy may only increase vaccine hesitancy without identifying patients at risk for COVID-19 vaccine reactions.

Otani IM ，Tsao LR ，Tang M 《-》

Patients with previous immediate hypersensitivity reactions to polyethylene glycol can safely receive the BNT162b2 mRNA COVID-19 vaccine.

Previous anaphylaxis or immediate allergic reaction to polyethylene glycol (PEG; also known as macrogol) is considered a contraindication to the BNT162b2 mRNA COVID-19 vaccine, which contains 50 ug of PEG at a molecular weight of 2000, and this component is thought to account for the higher rate of anaphylaxis seen with this vaccine (4.7 per million doses) than with other non-mRNA vaccines. However, there is evidence that both anaphylaxis to PEG and anaphylaxis to the Pfizer COVID-19 reaction may not be IgE-mediated, with patients with anaphylaxis to first dose of the Pfizer COVID-19 vaccine receiving their second dose of vaccine without no or milder reactions in a high-risk clinic setting. In New Zealand, non-PEG-containing COVID-19 vaccines were not available until late 2021. Therefore, we offered patients with known or suspected PEG anaphylaxis their first dose of Pfizer COVID-19 vaccine in a high-risk hospital clinic. Eleven patients with previous hypersensitivity to PEG (including eight with anaphylaxis) successfully received their first dose with mild or no reactions; all have now had their second doses in the community without significant reaction. Record review also showed that most patients with previous hypersensitivity reactions to pegylated asparaginase have also been successfully vaccinated. This demonstrates that previous PEG hypersensitivity, including anaphylaxis, does not exclude immunisation with the Pfizer COVID-19 vaccine.

Hurst M ，Jordan A ，Capstick J ，Brewerton M ，Cockroft R ，Ingram J ... -  《-》