A recent study tried to pinpoint what ingredient in the COVID-19 vaccines made by Pfizer and Moderna causes rare allergic reactions. It found that a widely-suspected culprit might not be at fault, and the vaccine reactions might be partially due to anxiety and other psychological factors.

Such reactions are extremely uncommon, happening two to five times per every 1 million people vaccinated in the U.S. But national surveys show that possible side effects remain a sticking point for hesitant people, and misinformation about what the shots contain is still rampant.

Scientists have long linked these adverse bodily responses to polyethylene glycol, an inactive ingredient that stabilizes messenger RNA (mRNA) — the genetic material that forms the backbone of the shots.

Seeking to address this theory, a team of allergy researchers at Northwell Health — New York’s largest health care provider — conducted allergy tests with polyethylene glycol, commonly known as PEG, to see if they could adequately predict if a patient will have a serious reaction to the vaccine.

“We thought it was most likely PEG, but that’s clearly not the case,” said Dr. Vincent Bonagura, a senior author of the study published October 23rd in the Annals of Allergy, Asthma & Immunology. “The vaccine is just made of a few other ingredients — lipids that are stabilizers, salts, sugars and the mRNA.”

PEG is nontoxic and found in a wide range of commercial applications, including the laxative a patient drinks before a colonoscopy, over-the-counter drugs such as Tylenol and even household cleaners. The ingredient hadn’t been used in vaccines prior to COVID-19, but it was found in cancer medicine.

Only a small amount of PEG is present in vaccines, and sensitivity to it is “super rare,” according to Dr. Joshua Milner, Chief of Pediatric Allergy, Immunology and Rheumatology at Columbia New York-Presbyterian. Determining a PEG allergy can also be challenging and is often misdiagnosed. The Northwell Health study confirmed that the current skin test for PEG allergy is an inaccurate predictor for an allergic reaction to COVID-19 vaccines.

Lead author Dr. Blanka Kaplan said false positives on the allergy test were more common than expected among their sampling of 113 participants, who all reported reactions to their first doses of Pfizer or Moderna.

As a result, patients who tested positive on the skin exam were given an additional test of drinking a large dose of PEG, the gold standard for confirming the allergy. No participant tested positive during this follow-up.

“This doesn’t mean that a patient with a known allergy to PEG won’t have a severe reaction,” said Dr. Purvi Parikh, an infectious disease allergist and immunologist at NYU Langone. “They absolutely can. It’s just really rare.”

The study authors and the allergy experts who spoke to WNYC/Gothamist agreed that they didn’t think PEG was linked to most of the reactions they see with the mRNA vaccines. But they weren’t sure what the cause could be either.

“What else could it be besides PEG?” said Dr. Parikh. “The vaccine has only a few ingredients, and it’s even rarer to be allergic to the other ingredients, sugars and salts. And the mRNA is harmless.”

Some parts of these reactions might also be psychological. Anxiety from needles and the fear of COVID-19 may be the kindling for most responses, both study authors and experts pointed out.

“Not every physiological response is an allergy,” said Dr. Milner. “Blushing when you’re embarrassed is not an allergic reaction.”

And neither is vomiting when repulsed nor shortness of breath during a panic attack. In fact, during the vaccine trials, those given the placebo —essentially an injection of salt water— reported reactions as extreme as anaphylaxis.

“I can’t come up with another way of explaining a reaction to the placebo,” said Dr. Milner. “It must be anxiety from getting a needle in your arm, especially around COVID. The body just thinks it needs to protect itself.”

Among about 100 participants who took a first dose in the study, more than four out of five — 86% — received a second dose without notable reactions. Dr. Bonagura said there was a lot of “hand-holding” with patients during their second doses, which may explain the lack of side effects. The doctor’s presence through the inoculation and the proceeding observation period could have helped alleviate patient fears. But participants with a history of allergic reactions also took antihistamines before their second doses.

The study also found that confirmed, severe reactions occurred predominantly in women with a history of allergies, and two-thirds had asthma. Men were more likely to get hives.

Dr. Kaplan suspects that underlying conditions, such as asthma, may flare up due to vaccination. She said this happens with all vaccines, including the flu. Any time the immune system is provoked into action, it can exacerbate a latent disease.

Despite allergies and underlying diseases, the study indicated that these patients could safely be vaccinated as long as their conditions are well controlled.

“The main message is there is no question that these vaccines save lives,” said Dr. Kaplan. “The majority of people can definitely receive vaccines safely, and if those people have concerns, they should talk to an allergist.”