The National Institutes of Health (NIH) has launched a study to assess whether people with a past history of serious allergies are more likely to have a bad reaction to the mRNA COVID-19 vaccines manufactured by Moderna and Pfizer/BioNTech.
Since the approval of both the Moderna and Pfizer/BioNtech mRNA vaccines by the FDA, many millions of doses of these vaccines have been administered to U.S. citizens. While they generally appear to be very safe and effective, with most people only experiencing mild reactions such as short-term injection site pain, a few people have experienced more severe side effects such as anaphylaxis.
An analysis of vaccine data published at the end of January by the CDC reports a rate of severe allergic anaphylaxis of 11.1 (21 cases overall) and 2.5 cases (10 cases overall) per 1 million vaccinations for the Pfizer/BioNTech and Moderna vaccines, respectively. These cases have mostly occurred in people with previous allergies and the majority were in women.
While these numbers are very low, it is important to investigate any possible links to the vaccines, which prompted the initiation of the current study. The aims of the Phase II study are to assess whether people who are already highly allergic or have a mast cell disorder – where patients have anaphylaxis symptoms due to mast cell dysfunction and not allergens – are at increased risk of an immediate systemic reaction after being given either of the mRNA vaccines.
“The public understandably has been concerned about reports of rare, severe allergic reactions to the Moderna and Pfizer-BioNTech COVID-19 vaccines,” said Anthony Fauci, M.D., director of the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health (NIH), in a press statement.
“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 two vaccines. However, for most people, the benefits of COVID-19 vaccination far outweigh the risks.”
The researchers running the study aim to recruit 3,400 adults aged 18-69 years from different allergy centers around the U.S. The aim is for the study to comprise 60% participants who either have a history of severe allergies or a mast cell disorder and 40% participants who do not have a history of allergies or who have mild allergies, but no history of a mast cell disorder. Because most of the reported cases of anaphylaxis have been in women, the study aim is to over recruit women and aim for two thirds women and one third men in the final cohort.
For the purposes of the study, a history of ‘severe’ allergies will be defined as any that have occurred in the previous 5 years that are related to food, insect stings or allergen immunotherapy that require treatment with epinephrine, or a history of immediate allergic reactions to vaccines or other drugs in the same time period.
The study will initially be fully blinded, with neither clinicians or patients knowing who is in which group. One third of participants in both groups will be randomly assigned to receive the Pfizer/BioNTech vaccine or the Moderna vaccine. The remaining third of participants in both the allergic and the control groups will be split and half will receive a placebo followed by the Pfizer/BioNTech vaccine and half a placebo followed by the Moderna vaccine.
The aim is that all participants in the cohort will eventually receive two doses of one of the vaccines, with unblinding occurring three days after the second dose for all participants. Those allocated to a vaccine group will be told which one they had at this point and those initially given placebo will be scheduled for a second dose of vaccine.
Because of the high-risk nature of the allergic participants, the trial will be conducted with all necessary safety and medical equipment, as well as trained staff, readily available in case of need. Each participant will be closely monitored for 90 minutes after their first injection to assess if a systemic allergic reaction occurs.
Nasal swabs, blood and urine will be collected before each injection and blood and urine after each injection to give the investigators the opportunity to assess each participant’s systemic reaction, should one occur.