Adults with serious allergies or a mast cell disorder are no more likely to experience anaphylaxis after an mRNA COVID-19 vaccine than those without allergies, new research finds.
Plus, the study found that reactions to the vaccines that did occur were not “true” allergic reactions.
To discover whether people with allergies were at higher risk and if so, why, the National Institutes of Health (NIH) launched the study comparing COVID-19 vaccine reactions in highly allergic individuals and those without allergies.
The findings show that “people with a mast cell disorder or a history of severe allergies don’t have to be handled any differently, and they should definitely not be prevented from getting the vaccine,” says Dr. James R. Baker, a principal investigator of the study.
Researchers at multiple U.S. centers followed patients in real-time, as they received vaccinations. The first phase of the study was “blinded” and placebo-controlled – neither patients nor medical staff knew who got vaccine and who got placebo – meeting the gold standard for clinical research.
The data should put to rest any lingering concerns that people with a mast cell disorder or food, insect venom or drug allergies have about getting vaccinated, says Baker, the director of the Mary H. Weiser Food Allergy Center at the University of Michigan.
Millions of people with a history of severe allergies have received the Pfizer-BioNTech and Moderna COVID-19 vaccines without a problem since they were introduced in December 2020. But reports of rare cases of anaphylaxis gave rise to questions about whether a history of allergies or mast cell disorders could heighten risk for an mRNA vaccine reaction.
The small percentage of early reports of anaphylactic reactions to the shots were in women and in people with a history of allergies to a wide range of triggers, including foods, drugs and injectable medications.
The NIH study included 664 men and women ages 18 and older: 373 with serious allergies or a mast cell disorder, and 291 in a control group without allergies who were matched for age and gender. Mast cell disorder is a condition in which people experience episodes of anaphylaxis without a known allergy trigger.
Participants were randomly assigned to receive a first shot of either the Pfizer-BioNTech vaccine, the Moderna vaccine, or a placebo. For the second shot, everyone received one of the two vaccines. (Those given the placebo initially were later given the actual vaccination.)
Anaphylaxis with Placebo
There were nine anaphylactic reactions, all in women and all in the “high allergy” group, among the NIH study participants. However, the anaphylactic reactions occurred in both those who received the vaccine and the smaller group who got the placebo, and the rate was identical, Baker says.
Reactions were considered anaphylaxis if participants had two or more symptoms, including mild to moderate itch, hives, flushing, swelling, cough, runny nose, watering eyes, nausea or vomiting, within 90 minutes of vaccination. None experienced severe anaphylaxis.
No Biological Signs of Allergy
Researchers drew blood from each participant before and after vaccination, and at the time of any reactions. They were looking for markers in the blood that indicate allergic reaction, anaphylaxis or inflammation.
Yet none of the blood samples in those experiencing symptoms bore any biological signs of an allergic reaction or anaphylaxis. Researchers looked for elevated levels of serum tryptase, which indicates mast cell activation that occurs during anaphylaxis, and elevated levels of IgE antibodies, which indicates an IgE-mediated allergic reaction.
“These people had clinical symptoms of anaphylaxis but there is no biochemical evidence they are having ‘true’ anaphylactic reactions,” Baker says. “They are perceiving an allergic reaction, but the perception is as common with the placebo as with the vaccine.” He presented the study data on May 16, at the American Thoracic Society meeting in San Francisco. The National Institute of Allergy and Infectious Diseases (NIAID) was the NIH division overseeing the study.
Researchers also considered whether a prior infection with SARS-CoV-2, the virus that causes COVID-19, could lead someone to be among the few who reacted to the vaccine. But they found no association between people who had antibodies to the virus, indicating a prior infection, and reactions.
What About PEG?
Questions have been raised about the role of allergy to polyethylene glycol (PEG), an ingredient in the mRNA vaccines, in some reactions. But neither PEG nor a related compound, polysorbate, were a cause of vaccine-related anaphylaxis in the study, Baker says. None of those who experienced a reaction to the vaccine had elevated levels of PEG antibodies. And when researchers compared people who reacted with those who didn’t react, their PEG antibody levels were about the same.
The type of PEG used in the vaccines is different than the PEG that’s the cause of rare allergic reactions to constipation treatments and other consumer products.
“PEG antibodies are not a useful way to identify people at risk for allergic reactions,” Baker says.
What Explains the Reactions?
He reiterates that there has never been any connection between specific food or drug allergies and vaccine reactions. The mRNA vaccines do not contain any food or animal product proteins.
But what this study is able to show conclusively is that the reactions are not allergic in nature. So then: Why do a few people still experience symptoms such as shortness of breath, flushing, hives and upset stomach?
Since reactions were as likely with the placebo as the actual vaccine, “it opens the question as to whether or not these people are triggered by something involving the administration of the vaccine and not the vaccine itself,” Baker says.
Prior research has shown that range of stress and anxiety-related reactions can occur with vaccination. Also well-documented is the “nocebo effect” – if someone anticipates side effects or expects to react negatively to a vaccine, they may actually experience symptoms.
The research team will continue to analyze the study data to gain more insights.
COVID-19 Vaccines and Allergies Q&A
Dr. James R. Baker, a principal investigator on the NIH’s COVID-19 vaccine and allergies study, answers common questions on mRNA vaccines and allergies.
If a person didn’t get a COVID-19 vaccine over concern about a mast cell disorder or a past allergic reaction to an injectable drug, what can they take from these findings?
JRB: They have no additional risk from the vaccine as compared to anyone else. They should go ahead and get the vaccine because their risks from COVID without vaccination are much greater than any risk from the vaccine.
What if someone had a past reaction to another type of vaccine?
JRB: We aren’t seeing that people who have had past reactions to other vaccines are at any increased risk of reacting to the mRNA vaccines. That is what has also been reported by others as well in smaller, less-controlled studies.
If a person has a PEG or polysorbate allergy, is it safe to get an mRNA vaccine for COVID-19?
JRB: Yes. We tested for antibodies to PEG, which can indicate sensitization to PEG. We did not find an association with PEG antibodies, or evidence of a PEG immune response, with reactions to the vaccine in these patients. And polysorbate is clearly not a risk factor for this vaccine.
What can you say with certainty from this study about mRNA vaccines for COVID-19 and allergies of any kind?
JRB: They shouldn’t worry about having a reaction to the vaccine. They should just go get it, and there shouldn’t be any limitations.