Perspective from Aleena Banerji, MD
Perspective from Purvi Parikh, MD
Disclosures: Picard reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

January 07, 2022
3 min read

Patients with PEG allergies may tolerate mRNA COVID-19 vaccines

Perspective from Aleena Banerji, MD
Perspective from Purvi Parikh, MD
Disclosures: Picard reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.

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Allergists may offer mRNA COVID-19 vaccines to patients who are allergic to polyethylene glycol after discussing its risks and benefits, researchers of a case series wrote in The Journal of Allergy and Clinical Immunology: In Practice.

Polyethylene glycol (PEG) allergy is considered a contraindication for COVID-19 vaccines that use mRNA technology because they are formulated in lipid nanoparticles that include a PEGylated lipid, the researchers wrote.

“Patients allergic to PEG have a difficult choice to make regarding vaccination against COVID-19,” Matthieu Picard, MD, FRCPC, an allergist and immunologist in the division of clinical immunology and allergy at Hôpital Maisonneuve-Rosemont, told Healio.

“In Canada and the U.S., where mRNA vaccines are widely available, they are preferred over viral vector vaccines because the latter carry a small risk for vaccine-induced thrombotic thrombocytopenia. However, mRNA vaccines contain small amounts of PEG 2000, which could theoretically trigger an allergic reaction in patients allergic to PEG,” Picard, who is also an associate clinical professor at Université de Montréal, said.

Since vaccines have been available in Quebec, nine allergists in six hospitals evaluated 12 patients with confirmed or very likely PEG allergy who were offered an mRNA vaccine or the AstraZeneca vaccine after discussing its risks and benefits. Ten patients received an mRNA vaccine, and two received the AstraZeneca vaccine.

After a positive skin prick test or a positive drug provocation test, researchers confirmed PEG 3350 allergies in six patients. Two of these patients also had a positive intradermal test to diluted 1:100 Pfizer-BioNTech mRNA vaccine, which is nonirritant. The other four did not have skin tests for the vaccine.

Three of the patients with a confirmed PEG 3350 allergy received and tolerated the Pfizer-BioNTech mRNA vaccine, and one tolerated and received the Moderna mRNA vaccine. The other two patients with a confirmed allergy received the AstraZeneca vaccine.

The other six patients with likely but unconfirmed PEG 3350 allergies received mRNA vaccines and tolerated them in a single step. One of these patients, however, experienced a second lifetime anaphylaxis to PEG 3350 between the first and second doses of the Moderna vaccine and subsequently received the second Moderna dose in five steps without a reaction. Another reported a very mild and limited skin reaction with the second Pfizer-BioNTech dose, although it was deemed unlikely to be allergic.

“We found that 10 patients with a confirmed or highly likely PEG allergy could tolerate mRNA vaccines,” Picard said.

“Surprisingly, two patients had positive skin tests to the Pfizer-BioNTech vaccine but tolerated it. No patient in our case series of PEG-allergic patients had an allergic reaction to a COVID-19 vaccine,” he added.

The researchers hypothesized that the lack of reactivity may be because the molecular weight and PEG doses in these mRNA vaccines were below the patients’ reaction thresholds.

Further, the researchers wrote, the amounts of PEG in the vaccines as well as its administration routes and molecular weight seem to influence the risk for reaction. Each Pfizer-BioNTech vaccine dose includes 0.05 mg of PEG 2000 linked to a lipid. Moderna does not list the exact amount of PEG 2000 in its vaccine’s fact sheet, but the researchers assumed it is likely in the same range.

Eleven of the patients reported reactions to at least 28 mg of PEG 3350, but most of them were not tested to PEGs with molecular weights below 3350 or to polysorbate 80, which the researchers called structurally similar to PEGs with lower molecular weights.

The researchers concluded that allergists could offer mRNA vaccines to patients with PEG allergies following a discussion of their risks and benefits.

“Discussion should start with the important benefits provided by COVID-19 vaccination: reduction in the risk for infection, hospitalization and death of SARS-CoV-2 infection,” Picard said.

Health care providers should inform patients that the real risk of having an allergic reaction to the PEG component of the vaccine remains unknown, but that at least some PEG-allergic patients tolerate mRNA vaccines, Picard continued.

“They should be informed that, in the event of an allergic reaction, those reactions generally respond well to treatment and resolve completely after a few hours. They can also be offered vaccine administration in divided doses every 15 to 20 minutes, which can favor tolerance,” Picard said.

Finally, Picard added, health care providers can describe alternatives such as a viral vector vaccine or no vaccination and discuss the risks associated with them.

Noting that further studies are necessary to establish safety profiles in larger patient cohorts, Picard said that the researchers will continue to monitor the outcome of patients with PEG allergy referred for COVID-19 vaccination in their population.

For more information:

Matthieu Picard, MD, FRCPC, can be reached at