Inert ingredient related to allergic reactions to COVID-19 vaccines

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According to investigators at a major regional health center that was among the first to give the vaccines, a more common inert ingredient could be the cause of the rare allergic reactions reported in people who received mRNA COVID-19 vaccines.

According to a report by JAMA Network Open, blood samples from 10 out of 11 people with suspected allergic reactions reacted to polyethylene glycol (PEG), a component of Pfizer and Moderna’s mRNA vaccines.

In total, out of nearly 39,000 doses of mRNA COVID-19 vaccine administered, only 22 people suspected allergic reactions, investigators reported, noting that the reactions were generally mild and all had completely resolved.

These results should reassure people who do not choose a COVID-19 vaccine for fear of an allergic reaction, said the study’s lead author, Kari Nadeau, MD, PhD, director of the Parker Center for Allergy and Asthma Research at Stanford University , Stanford, California.

“We hope that the word will spread and that companies may consider making vaccines that contain other products that do not contain polyethylene glycol,” Nadeau said in an interview with Medscape Medical News.

PEG is a compound that is used in many products including pharmaceuticals, cosmetics, and foods. In the mRNA COVID-19 vaccines, PEG is used to stabilize the lipid nanoparticles that help protect and transport mRNA. However, use in this environment has been linked to allergic reactions in this and previous studies.

No immunoglobulin E (IgE) antibodies to PEG were detected in the 22 people suspected of having allergic reactions to the mRNA COVID-19 vaccine, but PEG immunoglobulin G (IgG) was present. This suggests that non-IgE-mediated allergic reactions to PEG might be related for most cases, Nadeau said.

This case series provides interesting new evidence to confirm previous reports that a mechanism other than the classic IgE-mediated allergic reaction is behind the suspected allergic reactions that occur after mRNA COVID-19 vaccination, said Aleena Banerji, MD, Associate Professor at Harvard Medical School and Clinical Director of the Drug Allergy Program at Massachusetts General Hospital in Boston.

“We need to further understand the mechanism of these reactions, but what we do know is that the IGE-mediated allergy to excipients like PEG is probably not the main cause,” said Banerji, who was not involved in the study, in an interview with Medscape.

In a research letter recently published in JAMA Internal Medicine, Banerji and co-authors reported that all individuals with immediate suspicion of allergic reactions to the mRNA COVID-19 vaccine tolerated the second dose, with a minority of patients (32nd) tolerating the second dose Symptoms were reported by 159 or about 20%).

“Again, this is very consistent with not having an IgE-mediated allergy, so everything seems to fit that picture,” said Banerji.

Nadeau and co-authors’ case series was based on the review of nearly 39,000 mRNA COVID-19 vaccine doses administered between December 18, 2020 and January 26, 2021. Most recipients of mRNA vaccines were close to Stanford health workers, according to the report.

Among the recipients of these doses, they identified 148 people who had ICD-10 anaphylactic codes recorded during the same period. Upon reviewing the medical records, investigators identified 22 people with suspected allergies and invited them to participate in a follow-up for allergies.

A total of 11 people were prick tested, but none of them tested positive for PEG or polysorbate 80, another excipient that has been linked to vaccine-related allergic reactions. One of the patients, according to the report, tested positive for the same mRNA vaccine that he had previously received.

The same 11 subjects were also subjected to a basophil activation test (BAT). In contrast to the skin test results, the BAT results were positive for PEG in 10 of 11 cases (or 91%) and positive for the administered vaccine in all 11 cases, the report shows.

High levels of IgG to PEG have been found in blood samples from people allergic to the vaccine. Investigators said it was possible that the BAT results were activated due to IgG via a complement activation-related pseudo-allergy, or CARPA, as suggested by some other researchers.

The negative prick test results for PEG, in contrast to the positive BAT results for PEG, suggest that the former may not be used as a predictive marker of potential vaccine allergy, according to Nadeau.

“The message for doctors is to be careful,” she said. “Don’t assume you’re out of the woods just because the person has a negative skin test for PEG or the vaccine itself, because the skin test would often be negative in those scenarios.”

The study was supported by a grant from the Asthma and Allergic Diseases Cooperative Research Centers, a grant from the National Institutes of Health, the National Institute of Allergy and Infectious Disease SARS Vaccine Study, the Parker Foundation, the Crown Foundation, and the Sunshine Foundation.

Nadeau reports that he has received grants from the National Institute of Allergy and Infectious Diseases; the National Institute of Heart, Lung and Blood; the National Institute for Environmental Health Sciences; and food allergy research and education; worked as director of the World Allergy Organization; worked as a consultant for Cour Pharma; Participation in the National Scientific Committee of the Immune Tolerance Network and in the clinical research centers of the National Institutes of Health; and co-founder of Before Brands, Latitude, Alladapt, and IgGenix outside of the work submitted.

Nadeau reports that patents for an oral formula for reducing the risk of food allergies and for the treatment of food allergies, for granulocyte-based methods for the detection and monitoring of immune system disorders, for methods and assays for the detection and quantification of pure subpopulations of whites Blood cells in immune system diseases and for microfluidic devices and diagnostic methods for allergy tests based on the detection of basophil activation.

Banerji has not disclosed any relevant financial relationships.

JAMA network open. Published online 17 September 2021. Full text

Andrew D. Bowser is a freelance medical journalist based in Philadelphia.

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