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

Anna R Wolfson; Lacey B Robinson; Lily Li; Aubree E McMahon; Amelia S Cogan; Xiaoqing Fu; Paige Wickner; Upeka Samarakoon; Rebecca R Saff; Kimberly G Blumenthal; Aleena Banerji

doi:10.1016/j.jaip.2021.06.010

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

J Allergy Clin Immunol Pract. 2021 Sep;9(9):3308-3320.e3. doi: 10.1016/j.jaip.2021.06.010. Epub 2021 Jun 22.

Authors

Affiliations

¹ Harvard Medical School, Boston, Mass; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass. Electronic address: awolfson@mgh.harvard.edu.
² Harvard Medical School, Boston, Mass; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
³ Harvard Medical School, Boston, Mass; Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass.
⁴ Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass.
⁵ Harvard Medical School, Boston, Mass; Division of Rheumatology, Allergy, and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Edward P. Lawrence Center for Quality and Safety, Massachusetts General Hospital, Boston, Mass.

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.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anaphylaxis* / diagnosis
COVID-19 Vaccines
COVID-19*
Excipients
Humans
RNA, Messenger
SARS-CoV-2
Skin Tests

Substances

COVID-19 Vaccines
Excipients
RNA, Messenger

Grants and funding

K01 AI125631/AI/NIAID NIH HHS/United States