TOPLINE

Systemic reactions that clinicians classified as allergic occurred within 90 minutes of messenger RNA COVID vaccination only in participants with a history of severe allergic reactions and/or mast cell disorders, though the difference from those without such histories was not statistically significant. Two participants in the same group also reacted after saline placebo administration, and laboratory tests turned up no clear sign of an allergic mechanism.

METHODOLOGY

• Researchers conducted a randomized trial to estimate the frequency of systemic allergic reactions after vaccination with the Pfizer-BioNTech or Moderna COVID vaccine in participants with a history of severe allergic reactions and/or a mast cell disorder and compare it with the frequency in those without this history.
• A total of 664 participants aged 12 years or older received at least one injection at 28 US allergy specialty centers; 373 (mean age, 41 years; 80% women) were in the history of severe allergic reactions and/or a mast cell disorder group and 291 (mean age, 33 years; 51% women) in the comparison group.
• Participants were assigned to receive two active doses of the Pfizer-BioNTech vaccine, two active doses of the Moderna vaccine, or a saline placebo followed by two active doses of one of the vaccines.
• The main endpoint was a systemic allergic reaction within 90 minutes of injection, as determined by allergy expert clinicians using the Consortium for Food Allergy Research grading scale.
• Blood and urine samples, taken before each injection and 30 to 60 minutes after any reaction (or at 60 minutes if none occurred), were tested for signs of allergic or other immune mechanisms.

TAKEAWAY

• Within 90 minutes of vaccination, reactions occurred only in those with a history of severe allergy and/or a mast cell disorder: 5 of 180 Pfizer-BioNTech recipients (2.8%) and 2 of 173 Moderna recipients (1.2%). No reactions occurred in the comparison groups for either of the vaccines; the differences were not statistically significant.
• Four of the seven reactions within 90 minutes were graded severe, and two participants in the allergy and/or a mast cell disorder group had a severe reaction after placebo. The reaction rates after first dose did not differ significantly between the placebo and either of the vaccines.
• Reactions reported between 90 minutes and 48 hours also occurred only in those with a history of severe allergy and/or a mast cell disorder and were significantly more common in them (P = .0041 for Pfizer-BioNTech; P = .0008 for Moderna).
• Laboratory tests found no clear evidence of mast cells, complement, or the kallikrein pathway activation in participants who reacted compared with matched participants who did not.

IN PRACTICE

"Although systemic reactions within 90 minutes or 48 hours occurred only in PSAR/MCD [prior severe allergic reactions and/or mast cell disorders] participants, similar reactions occurred after placebo. As no allergic or other immunologic mechanism was detected by extensive laboratory analysis, these events, despite the clinical characterization as systemic allergic reactions, are unlikely to represent reactions of a true allergic/immunologic origin," the authors wrote.

SOURCE

Alkis Togias, MD, with the National Institute of Allergy and Infectious Diseases, Rockville, Maryland, was the corresponding author of the study, which was published online on October 13 in The Journal of Allergy and Clinical Immunology.

LIMITATIONS

The trial planned to enroll 3400 participants but fell short because of delays in starting the study, and the small number of reactions limited the precision of the results. In addition, participants who had a reaction of grade 2 or higher after receiving an active vaccine dose did not receive a second dose; therefore, the researchers could not assess whether reactions would recur.

DISCLOSURES

The study was funded by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health through the Immune Tolerance Network. Most authors reported receiving grants from the institute during the study, and several reported receiving research support, consulting fees, or speaking fees or having other ties with a wide range of pharmaceutical companies. Study vaccines were provided by the Health and Human Services Coordination Operations and Response Element.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.