"We wanted to understand the spectrum of allergies to the new vaccines and understand what was causing them," said the study's senior author, Kari Nadeau, MD, PhD, the Naddisy Foundation Professor in 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 health care providers at Stanford soon after the vaccines received emergency use authorization from the Food and Drug Administration.
Most of those in the study who developed reactions were allergic to an ingredient that helps stabilize the COVID-19 vaccines; they did not show allergies to the vaccine components that provide immunity to the SARS-CoV-2 virus. Furthermore, these allergic reactions occurred via an indirect activation of allergy pathways, which makes them easier to mitigate than many allergic responses.
"It's nice to know these reactions are manageable," said Nadeau, who directs the Sean N. Parker Center for Allergy and Asthma Research at Stanford. "Having an allergic reaction to these new vaccines is uncommon, and if it does happen, there's a way to manage it."
The study's lead author is former postdoctoral scholar Christopher Warren, PhD, now an assistant professor at Northwestern University Feinberg School of Medicine.
The research also suggests how vaccine manufacturers can reformulate the vaccines to make them less likely to trigger allergic responses, Nadeau said.
Delivery of protein-making instructions
The mRNA-based COVID-19 vaccines provide immunity via small pieces of messenger RNA that encode molecular instructions for making proteins. Because the mRNA in the vaccines is fragile, it is encased in bubbles of lipids -- fatty substances -- and sugars for stability. When the vaccine is injected into someone's arm, the mRNA can enter nearby muscle and immune cells, which then manufacture noninfectious proteins resembling those on the surface of the SARS-CoV-2 virus. The proteins trigger an immune response that allows the person's immune system to recognize and defend against the virus.
Estimated rates of severe vaccine-related anaphylaxis -- allergic reactions bad enough to require hospitalization -- are 4.7 and 2.5 cases per million doses for the Pfizer and Moderna vaccines, respectively, according to the federal Vaccine Adverse Event Reporting System. However, the federal system doesn't capture all allergic reactions to vaccines, tending to miss those that are mild or moderate.
For a more complete understanding of allergic reactions to the new vaccines -- how common they are, as well as how severe -- the research team examined the medical records of health care workers who received 38,895 doses of mRNA-based COVID-19 vaccines at Stanford Medicine between Dec. 18, 2020, and Jan. 26, 2021. The vaccinations included 31,635 doses of the Pfizer vaccine and 7,260 doses of the Moderna vaccine.
The researchers searched vaccine recipients' medical records for treatment of allergic reactions and identified which reactions were linked to the vaccines. Twenty-two recipients, 20 of them women, had possible allergic reactions, meaning specific symptoms starting within three hours of receiving the shots. The researchers looked for the following symptoms in recipients' medical records: 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 had reactions that met diagnostic criteria for an allergic reaction. Three recipients received epinephrine, usually given for stronger anaphylaxis. All 22 fully recovered.