COMMENTARY COVID Vaccine Anaphylaxis: Who Is at Risk? Gary J. Stadtmauer, MD DISCLOSURES January 29, 2021

Some of the celebration and excitement over the approval of the COVID vaccines has been dampened by recent reports of allergic complications. Twenty-one cases of confirmed anaphylaxis were identified after the first 1.8 million doses of the Pfizer-BioNTech vaccine were administered (roughly 1 in 87,000 injections). Though rare, this is substantially higher than the risk associated with other vaccines (1.3 per million).

So far, the majority of episodes of anaphylaxis occurred within 30 minutes of receiving the vaccine and readily responded to treatment. Of 21 identified case reports, five patients were food allergic, of whom three also had a history of drug allergy. A total of 12 patients had had prior allergic reactions to medications or vaccines, and one patient had environmental allergies.

As for the Moderna vaccine, a couple of cases of delayed facial swelling have occurred without serious consequences. The Centers for Disease Control and Prevention (CDC) now recommends a brief period of observation after vaccination in a facility that is capable of and prepared to treat anaphylaxis.

So, what's the most likely cause of these reactions, and how can we keep our patients safe? Here are the answers to some questions you might have.

Are Vaccine Allergies Common?

Vaccine allergy is rare. The cause of these rare allergic reactions to vaccines is usually not the antigen but an excipient — additives that may include antibiotics, preservatives, or adjuvants. Meat proteins (gelatin and, rarely, alpha-gal) have also been identified as causes of IgE-mediated reactions in vaccines with higher gelatin content (MMR and VZV). Therefore, in some instances, atopy (especially food allergy) may be a risk factor for reactions to certain vaccines. On the other hand, influenza vaccine cultured in eggs contains so little egg allergen that it is no longer a concern for patients with even severe egg allergy.

What Might Be Causing COVID-19 Vaccine Anaphylaxis?

It was recently proposed that the cause of these reactions is the known allergen polyethylene glycol (PEG), which is present in both the Moderna and Pfizer vaccines to help stabilize the mRNA. PEG has been identified as the cause of reactions to colonoscopy preparations; stool softeners (such as Miralax); and medications, including topical and parenteral corticosteroids, as well as PEG-coated tablets and toothpaste. The high molecular weight of PEG may be immunogenic. Both IgE and IgG antibodies to these excipients, along with positive skin tests, support this.

Who Is At Risk for COVID-19 Vaccine Anaphylaxis?

This remains to be determined and may be different for each COVID-19 vaccine. Operating under the assumption that the causative agent may be PEG, then patients with a history suspicious for IgE-mediated reactions to a stool softener, colonoscopy prep, and other products containing PEGylated products may be considered at risk.

How Do You Evaluate Patients Who Could Be At Risk?

Skin prick and intradermal testing to PEG-3350 (the polyethylene glycol in Miralax stool softener) has been reported and was positive in some patients with a history of anaphylaxis to this product; the skin test resulted in a mild urticarial rash with dyspnea and diffuse pruritus. Because there is at least some experience with PEG skin testing, this could be done in patients with a questionable history of PEG allergy. But how to proceed beyond that would still be uncharted territory.

How Should We Manage Higher-Risk Patients?

The CDC recommends that patients who have an anaphylactic reaction to the first dose of the COVID-19 vaccine not receive the second dose. When the diagnosis is in doubt — for example, in the setting of a possible vasovagal reaction post-vaccination — measuring serum tryptase (or SC5b-9, the terminal complement complex) may confirm the diagnosis of anaphylaxis. I advise interpretation of the test result in consultation with an allergist-immunologist. A history of an anaphylactic reaction to any polysorbate (such as PEG) is also a contraindication to the Pfizer and Moderna vaccines.

How Should We Manage Patients With Vaccine Contraindications?

The Johnson & Johnson COVID-19 vaccine utilizes an adenovirus vector rather than mRNA. For patients who may have had anaphylaxis after the first dose but in whom the reaction is seriously in doubt, an allergist could consider performing a scratch test with sequential challenge. It's debatable whether that is worth the risk, because the first vaccine dose has moderate efficacy and an alternative vaccine is on the horizon.

Gary J. Stadtmauer, MD, is an allergist-immunologist in New York City. His areas of clinical interest include asthma, eczema, chronic cough, and sinusitis. He has been a Medscape contributor since 2014.