A new National Institutes of Health phase 2 trial aims to assess whether people with a history of allergies or a mast cell disorder are at a higher risk of systemic allergic reactions to the Pfizer-BioNTech and Moderna COVID-19 vaccines.
Most of the rare, severe allergic reactions to the 2 messenger RNA (mRNA) COVID-19 vaccines have been in people with a history of allergies, many of whom had previous anaphylaxis. In mast cell disorders, abnormal or overly active mast cells, a type of white blood cell, can cause life-threatening reactions that look like anaphylaxis.
The study will enroll 3400 adults aged 18 to 69 years at allergy research centers nationwide. About 60% of participants will have a history of anaphylaxis within the past 5 years or a mast cell disorder diagnosis, while the other 40% will have no history of allergy or mast cell disease. Women will comprise about two-thirds of each group because anaphylaxis after vaccination in general, and after vaccination with mRNA vaccines in particular, is more common among women.
People in each group will be randomized to receive 2 doses of the Pfizer-BioNTech vaccine, 2 doses of the Moderna vaccine, a placebo shot followed by 1 dose of the Pfizer-BioNTech vaccine, or a placebo shot followed by 1 dose of the Moderna vaccine. Investigators at each site are allergists trained to recognize and treat anaphylaxis.
Participants will be observed for at least 90 minutes after each injection in case they have any type of reaction. Investigators will compare the percentage of participants in the 2 study groups—those with allergies or mast cell disorders and those without them—who have a systemic allergic reaction.
“The information gathered during this trial will help doctors advise people who are highly allergic or have a mast cell disorder about the risks and benefits of receiving these 2 vaccines,” Anthony Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said in a statement. “However, for most people, the benefits of COVID-19 vaccination far outweigh the risks.”