This is a challenging task for researchers, who hope to get an answer within a matter of weeks. The study will recruit volunteers who have had a history of severe allergic reactions and who will receive the vaccine under close clinical supervision, according to Daniel Rotrosen, director of the Division of Allergy, Immunology and Transplantation at the National Institute of Allergy and Infectious Diseases.
“This is not a simple study design,” Rotrosen told The Washington Post. “We expect to be looking at highly allergic individuals. They will be not necessarily so easy to recruit, either. A lot still needs to be done to be sure we have the optimal study design. That said, we’re trying to move as quickly as we can, for obvious reasons.”
Both the Pfizer and Moderna vaccines have passed strict safety reviews. During the randomized trials, no volunteers had severe allergic reactions, although people with a history of anaphylaxis were excluded.
Government officials and medical experts say these rare reactions should not deter the public from vaccination, although the standard guidance is that people who get the shot should linger at the clinic or doctor’s office for 15 minutes — 30 minutes if they have a history of severe allergic reactions. Anaphylaxis can be quickly reversed with epinephrine and other medicines.
The vaccines do not contain the coronavirus itself, but rather synthetic messenger RNA that instructs cells to manufacture a protein that looks like the spike protein of the coronavirus. The immune system, in turn, responds by producing antibodies to that protein, creating sentries against infection by the real virus. The RNA does not interact with or alter a person’s DNA.
Milder side effects, such as headaches, fatigue or pain at the injection site, are common and pass within a day or two, and they are a sign that the vaccine is working to stimulate the immune system.
Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research, said Friday that one leading suspect for the bad reactions is a chemical widely used in medicines, cosmetics and other household products and that is part of the vaccine formula: polyethylene glycol. More than 2 out of 3 people have antibodies to PEG, as it’s known, but allergic reactions are extremely rare.
They’re so rare that, according to Rotrosen, there would be no practical way to round up enough PEG-allergic volunteers to conduct the proposed study. So the volunteers will be from a broader cohort of people with severe allergic reactions to anything.
Rotrosen’s institute, which is helmed by Anthony S. Fauci, had conducted a series of Zoom meetings in recent days with representatives of the Food and Drug Administration as well as from Pfizer and Moderna. Also on the calls have been academic researchers and scientists with knowledge of allergic reactions, including to PEG and to lipid nanoparticles, which are used in the vaccines.
In an email Sunday, Rotrosen said the study probably would involve several hundred volunteers at clinical sites across the country.
“Such a study would include baseline clinical and laboratory evaluations of participants, administration of the vaccine(s) under close observation, and clinical and laboratory follow-up to assess immune or allergic reactivity,” he wrote.
N. Franklin Adkinson, a professor of allergy and immunology at Johns Hopkins Medical School who has been participating in the planning sessions, said PEG is the most obvious suspect because it is known to be capable of triggering a severe allergic reaction. One possibility is that such reactions are underreported and therefore more common than doctors realize.
The issue of anaphylaxis produced headlines almost immediately after health-care workers in the United Kingdom began receiving the Pfizer vaccine shortly after it was authorized. Both of the health-care workers who had severe reactions had histories of anaphylaxis.
It was a third case of anaphylaxis, involving a health-care worker in Alaska, that many experts are focused on. The woman, described only as middle-aged and an employee of Bartlett Regional Hospital in Juneau, suffered not just one but multiple phases of anaphylaxis, each requiring medical treatment with epinephrine (adrenaline) and other medication before she fully recovered. The first symptoms began 10 minutes after she received an injection of the Pfizer vaccine. Importantly, she had no history of allergic reactions.
Adkinson described that case as “a very severe reaction that’s clearly not an overinterpretation of the facts because she had to be hospitalized.”
That case is being examined closely.
Adkinson suggested that health-care workers who routinely handle “PEGylated” medications may have unusually high levels of antibodies to them.
He said his patients who suffer from allergies have been calling him to ask whether they should take the vaccine.
“I would tend to be conservative and wait until we have explored this a little further,” he said. “As a physician interested in public health, I’m very much concerned about providing a balanced and accurate view so patients are not frightened away from taking the vaccine. We know already that the vast majority of patients will be able to tolerate it without any difficulty.”