NIH Researchers to Study Allergic Reactions to COVID-19 mRNA Vaccine

Severe allergic reaction is rare in any type of vaccine. But health authorities are taking steps to understand allergic reactions to the Pfizer or Moderna COVID-19 mRNA vaccine to ease concerns of those who may be hesitant to get their second or third shots.

The National Institute of Allergy and Infectious Diseases (NIAID) in March launched a clinical trial that is recruiting participants who had an allergic reaction to the first dose of mRNA vaccines.

The 100 study participants between 16 to 69 years old will receive a supervised second dose of vaccine, as well as a placebo on a following day, while being monitored for any reactions. 

“People who experienced an allergic reaction after receiving a COVID-19 mRNA vaccine may be hesitant to complete their vaccine regimen,” Anthony S. Fauci, MD, NIAID director and chief medical advisor to the president, said in a statement. “This study will help us determine if individuals who experienced moderate systemic allergic reactions can safely receive a second dose of a COVID-19 mRNA vaccine.”

Pamela A. Guerrerio, MD, PhD, head of NIAID’s Laboratory of Allergic Diseases and leader of the trial, said that life-threatening allergic reactions to mRNA vaccines are extremely rare—only about five cases per one million doses administered.

For people who had a severe or immediate allergic reaction to either the Pfizer or Moderna COVID-19 vaccine, the Johnson & Johnson vaccine is recommended instead, according to the Centers for Disease Control and Prevention (CDC).

Guerrerio told Verywell that allergic reactions were closely monitored during the early days of the COVID-19 vaccination campaign. But those reactions turned out to be rare, at two to five incidents per million doses, she said.

More women than men have shown COVID vaccine allergies, according to Guerrerio. “We have not really yet been able to identify any specific indications for risk, which is why the trial is so important,” she said.

She added that most people who have had a mild to moderate allergic reaction to the first dose will be able to tolerate the second dose. And some have taken antihistamine prior to their second dose to reduce potential allergy symptoms.

Another option is to receive the same vaccine but under the care of an allergist, especially if they had a life-threatening type of reaction, such as difficulty breathing, Guerrerio said. Allergists typically give a tiny dose and wait 15 to 30 minutes before continuing with a slightly larger dose, with emergency medication on hand.

In addition to monitoring reactions of patients to second doses and placebos, researchers will also do immunology studies to learn more about the mechanisms behind the reactions. They will examine whether anxiety affects the outcome of allergic reactions as well.

Allergic reactions to the mRNA vaccines are presumably caused by allergic antibodies called immunoglobulin E (IgE), which are responsible for the symptoms of an allergic reaction, Guerrerio said.

The mRNA vaccines also are the first vaccines to contain a component called polyethylene glycol (PEG), which were thought to be responsible for the allergic reactions. However, there have been very few documented cases of severe allergic reaction to PEG following COVID-19 vaccination. In one rare case, U.K. researchers suggested screening patients who may have existing PEG allergy with a skin prick test prior to vaccination.

Guerrerio emphasized that current data are extraordinarily clear that the vaccine is a very effective strategy to prevent severe COVID-19. “So even if people did have any kind of reaction to the first vaccine dose, it is critical that they talk to their providers on ways to be fully vaccinated with the second dose and boosters.” she said.

The NIH researchers hope to have their study completed by the end of 2022.

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