Allergic reactions to COVID-19 mRNA vaccines are rare and usually mild, according to a study late last week in JAMA Network Open.
Stanford University researchers led the study of 22 reported allergic reactions to the first 38,895 doses of the Pfizer/BioNTech and Moderna COVID-19 vaccines given to healthcare workers from Dec 18, 2020, to Jan 26, 2021 (less than six hundredths of a percent). Of all vaccinations, 80.6% were of the Pfizer vaccine, while 18.7% were of Moderna. The study population was 60% women, 64% White, 2% Black, 20% Asian, 16% younger than 50 years, and 54% aged 70 and older.
According to the national Vaccine Adverse Event Reporting System (VAERS), the rate of severe vaccine-related anaphylaxis, or a serious allergic reaction that requires hospitalization, is 4.7 per million for the Pfizer vaccine and 2.5 per million for Moderna. But the authors noted that VAERS tends not to capture mild or moderate allergic reactions to vaccines.
Women at higher risk for allergy
Of the 22 allergic reactions occurring within 3 hours of receiving a vaccine dose, 20 occurred in women. Symptoms indicating a possible allergic reaction included hives; swelling of the mouth, lips, tongue, or throat; shortness of breath, wheezing, or chest tightness; and changes in blood pressure or loss of consciousness.
Seventeen of the 22 reactions met the diagnostic criteria for likely anaphylaxisThree vaccinees received epinephrine, a drug typically given for severe anaphylaxis. All patients recovered.
Fifteen of the 22 vaccinees with allergic reactions had a history of allergy to antibiotics (10), foods (9), medications excluding antibiotics (8), or a combination of these. Five patients had a history of anaphylaxis, 3 of them to antibiotics, 1 to pork, and 1 to peanuts.
Current Centers for Disease Control and Prevention guidelines advise anyone who had a severe allergic reaction to any component or the first dose of either mRNA COVID-19 vaccine to avoid further exposure to it.
Opportunities for vaccine reformulation
In follow-up basophil activation testing, 10 of 11 vaccinee blood samples reacted to the inert vaccine ingredient polyethylene glycol (PEG), which is used in both the Pfizer and Moderna vaccines (none tested positive via skin prick test). Because all 11 vaccinees had antibodies against PEG in their blood, the authors said that they were probably already sensitive to it from previous exposure.
"What's important is what we didn't find, as much as what we did find," senior study author Kari Nadeau, MD, PhD, said in a Stanford Medicine press release. "It does not seem that the mRNA itself causes the allergic reactions."
The study results also suggest that the reactions were mediated by immunoglobulin G (IgG) antibodies and basophils, which are typically managed with antihistamines, fluids, corticosteroids, and observation. This means that many vaccinees who had allergic reactions to the first dose will be able to safely receive the second dose under medical supervision, the researchers said.
"It's nice to know these reactions are manageable," Nadeau said. "Having an allergic reaction to these new vaccines is uncommon, and if it does happen, there’s a way to manage it."
The study also suggests how vaccine makers can reformulate the vaccines to make them less allergenic, Nadeau said. PEG is a common ingredient in household products, cosmetics, and medications, to which women likely have broader exposure than men, the researchers said. This not only could explain the sex difference in vaccine reactions, but it could also allow manufacturers to reformulate the vaccines with less allergenic stabilizers.
"If confirmed by more systematic future investigations, these findings highlight potential opportunities for patient risk stratification and for alternatives in vaccine manufacturing; furthermore, they can inform ongoing mRNA vaccine development, including that of possible COVID-19 booster shots to protect against emerging disease variants," the authors concluded.