COVID-19 vaccine allergies rare, usually mild and treatable, study finds

Allergic reactions to newer mRNA-based COVID-19 vaccines are rare, usually mild and treatable, and they shouldn’t deter people from getting the vaccine, according to research from Stanford University School of Medicine.

The results will be published online on September 17 in JAMA network open.

We wanted to understand the spectrum of allergies to new vaccines and understand what causes them. “

Kari Nadeau, MD, PhD, study lead author, Naddisy Foundation professor of pediatric food allergy, immunology and asthma

The study analyzed 22 potential allergic reactions to the first 39,000 doses of Pfizer and Moderna COVID-19 vaccines given to healthcare providers at Stanford shortly after the vaccines were approved for emergency use of the Food and Drug Administration.

Most of the people in the study who developed reactions were allergic to an ingredient that helps stabilize COVID-19 vaccines; they did not show allergies to the components of the vaccine that confer immunity to the SARS-CoV-2 virus. Additionally, these allergic reactions occurred via indirect activation of allergic pathways, making them easier to mitigate than many allergic responses.

“It’s nice to know that these reactions are manageable,” said Nadeau, who heads the Sean N. Parker Center for Allergy and Asthma Research at Stanford. “Having an allergic reaction to these newer vaccines is rare, and if it does, there is a way to manage it.”

The lead author of the study is former postdoctoral researcher Christopher Warren, PhD, now an assistant professor at Northwestern University Feinberg School of Medicine.

The research also suggests how vaccine makers can reformulate vaccines to make them less likely to trigger allergic reactions, Nadeau said.

Delivery of protein manufacturing instructions

COVID-19 mRNA-based vaccines provide immunity via small pieces of messenger RNA that encode molecular instructions to make proteins. Because mRNA in vaccines is fragile, it is locked in lipid bubbles -; fat body -; and sugars for stability. When the vaccine is injected into someone’s arm, mRNA can enter neighboring muscle and immune cells, which then make non-infectious proteins resembling those found on the surface of the SARS-CoV-2 virus. Proteins trigger an immune response that allows a person’s immune system to recognize and defend against the virus.

Estimated rates of severe vaccine-related anaphylaxis -; allergic reactions severe enough to require hospitalization -; are 4.7 and 2.5 cases per million doses for Pfizer and Moderna vaccines, respectively, according to the federal vaccine adverse event reporting system. However, the federal system does not capture all allergic reactions to vaccines, tending to ignore mild or moderate ones.

For a more complete understanding of allergic reactions to new vaccines -; how common they are and how serious they are; the research team reviewed the medical records of healthcare workers who received 38,895 doses of mRNA-based COVID-19 vaccines at Stanford Medicine between December 18, 2020 and January 26, 2021. Vaccinations included 31,635 doses of Pfizer vaccine and 7,260 doses of Moderna vaccine.

Researchers searched medical records of vaccine recipients for treatment of allergic reactions and identified vaccine-related reactions. Twenty-two recipients, including 20 women, had possible allergic reactions, meaning specific symptoms starting within three hours of receiving the injections. The researchers looked for the following symptoms in the medical records of the recipients: hives; swelling of the mouth, lips, tongue or throat; shortness of breath, wheezing, or chest tightness; or changes in blood pressure or loss of consciousness. Only 17 of the 22 recipients presented reactions that met the diagnostic criteria for an allergic reaction. Three recipients received epinephrine, usually given for stronger anaphylaxis. All 22 have fully recovered.

Of the 22 beneficiaries, 15 had a history of allergic reactions documented by a physician, including 10 to antibiotics, nine to food and eight to non-antibiotic medications. (Some recipients had more than one type of allergy.)

The researchers performed follow-up lab tests on 11 people to determine what type of allergic reaction they had, as well as what triggered their allergy: was it one of the inert sugar or fat ingredients in the bubble, or something else in the vaccine?

Study participants underwent skin tests, in which a clinician injected small amounts of potential allergens -; lipids, sugars (polyethylene glycol or polysorbates) or whole vaccine -; in the skin. The skin test detects allergic reactions mediated by a form of antibody known as immunoglobin E or IgE; these reactions are usually associated with the most severe allergies.

None of the recipients responded to skin tests to inert vaccine ingredients, and the skin of a single recipient responded to the entire COVID-19 vaccine. Follow-up blood tests showed that vaccine recipients did not have significant levels of IgE antibodies against vaccine ingredients.

Since skin tests did not explain the mechanism of the allergic reactions of the recipients, the investigators performed another type of diagnostic test. Vaccinees provided blood samples for testing for allergic activation of immune cells called basophils. Blood samples from 10 of the 11 participants showed a reaction to the inert ingredient polyethylene glycol (PEG), which is used in both Pfizer and Moderna vaccines. Additionally, all 11 recipients exhibited basophil activation in response to whole mRNA vaccine when mixed with their own basophils.

All 11 subjects had elevated levels of IgG antibodies against PEG in their blood; IgG antibodies help activate basophils under certain conditions, and this finding suggests that individuals were likely sensitive to PEG prior to receiving their vaccines.

“What is important is what we didn’t find, as much as what we found,” said Nadeau. “It does not appear that the mRNA itself causes the allergic reactions.”

Additionally, the data suggests that reactions to COVID-19 vaccines were generally not the most serious form of allergic reaction, which is good news in terms of vaccine safety, she said. Allergic reactions mediated by IgG and basophils can be managed with antihistamines, fluids, corticosteroids and close monitoring, which means that many people who have had a reaction to their first dose of the vaccine can safely receive a second dose under medical supervision.

PEG is widely used as a stabilizer in household products, cosmetics and medicines, with women being more likely to be exposed to large amounts of the substance, which may be why more vaccine allergies have been observed. in women. (Repeated exposures to a substance can sometimes sensitize the immune system and cause allergies.) Since most reactions involved PEG rather than the active ingredients in the vaccine, it is likely that vaccine manufacturers could reformulate vaccines with different stabilizers less likely to cause allergies. , says Nadeau.