First-Dose mRNA COVID-19 Vaccine Allergic Reactions: Limited Role for Excipient Skin Testing

Abstract

Background: The Centers for Disease Control and Prevention state that a severe or immediate allergic reaction to the first dose of an mRNA COVID-19 vaccine is a contraindication for the second dose.

Objective: To assess outcomes associated with excipient skin testing after a reported allergic reaction to the first dose of mRNA COVID-19 vaccine.

Methods: We identified a consecutive sample of patients with reported allergic reactions after the first dose of mRNA COVID-19 vaccine who underwent allergy assessment with skin testing to polyethylene glycol (PEG) and, when appropriate, polysorbate 80. Skin testing results in conjunction with clinical phenotyping of the first-dose mRNA COVID-19 vaccine reaction guided second-dose vaccination recommendation. Second-dose mRNA COVID-19 vaccine reactions were assessed.

Results: Eighty patients with reported first-dose mRNA COVID-19 vaccine allergic reactions (n = 65; 81% immediate onset) underwent excipient skin testing. Of those, 14 (18%) had positive skin tests to PEG (n = 5) and/or polysorbate 80 (n = 12). Skin testing result did not affect tolerance of the second dose in patients with immediate or delayed reactions. Of the 70 patients who received the second mRNA COVID-19 vaccine dose (88%), 62 had either no reaction or a mild reaction managed with antihistamines (89%), but 2 patients required epinephrine treatment. Three patients with positive PEG-3350 intradermal (methylprednisolone) testing tolerated second-dose mRNA COVID-19 vaccination. Refresh Tears caused nonspecific skin irritation.

Conclusions: Most individuals with a reported allergic reaction to the first dose of mRNA COVID-19 vaccines, regardless of skin test result, received the second dose safely. More data are needed on the value of skin prick testing to PEG (MiraLAX) in evaluating patients with mRNA COVID-19 vaccine anaphylaxis. Refresh Tears should not be used for skin testing.

Keywords: Anaphylaxis; COVID-19; COVID-19 vaccine; Drug allergy; Excipient allergy; PEG allergy; Polysorbate allergy; Skin testing; Vaccine allergy.

Figure 1

Patients who were skin tested owing to symptoms after mRNA COVID-19 vaccination that were concerning for an allergic reaction. (A) All patients. (B) Patients with immediate allergic reactions. (C) Patients with delayed allergic reactions. ∗Three patients who had positive skin testing to both polyethylene glycol (PEG) and polysorbate are represented in the PEG category only for the purpose of illustration. †One patient did not receive the next dose in the series and instead received Janssen. ‡Two patients had grade 0 reactions and 1 had a grade 1 reaction. §Three patients had a grade 0 reaction, 9 had a grade 1 reaction, and 3 had a grade 2 reaction. ‖Two patients who had positive skin testing to both PEG and polysorbate are represented in the PEG category only for the purpose of illustration. ¶One patient did not receive the next dose in the series and instead received Janssen. #One patient had a grade 0 reaction and 1 had a grade 1 reaction. ∗∗Two patients had a grade 0 reaction, 8 patients had a grade 1 reaction, and 3 had a grade 2 reaction. ††One patient who had positive skin testing to both PEG and polysorbate is represented in the PEG category only for the purpose of illustration. ‡‡One patient had a grade 0 reaction. §§One patient had a grade 0 reaction and 1 had a grade 1 reaction.

Figure 2

Management of patients who present with symptoms concerning for an allergic reaction to the first dose of mRNA COVID-19 vaccine. Use of Janssen vaccine (if available) may be appropriate after allergic reaction to the first dose of mRNA COVID-19 vaccine if allergy evaluation is not feasible or owing to shared decision-making between the patient and physician. PEG, polyethylene glycol. ^∗Same COVID-19 vaccine manufactured as first dose. ^†Limited supply of Janssen COVID vaccine; only use when clinically necessary.

Figure E1

Skin testing protocol for polyethylene glycol (PEG) using MiraLAX for epicutaneous testing without PEG intradermal testing and PEG and polysorbate 80.