Systemic Allergic Reactions to mRNA COVID-19 Vaccines: A Randomized Placebo-controlled Trial.

BACKGROUND

COVID-19 mRNA vaccines were associated in early reports with more allergic reactions than most vaccines, especially in people with allergic histories.

OBJECTIVE

To estimate the proportions of systemic allergic reactions to mRNA COVID-19 vaccines in people reporting prior severe allergic reactions to various allergens, and/or mast cell disorders (PSAR/MCD Group) and determine if proportions are higher than in non-PSAR/non-MCD (Comparison Group).

METHODS

We conducted a multi-center, randomized, double-blinded (for the initial injection), placebo-controlled trial in PSAR/MCD vs Comparison adults and adolescents. Participants received a double-blinded injection with Pfizer-BioNTech or Moderna COVID-19 vaccine or placebo, followed by unblinded vaccine injections. The primary outcome was the incidence of clinically-determined systemic allergic reactions within 90 minutes after injection.

RESULTS

The trial enrolled 723 participants of a planned 3400, with 664 (56% PSAR/MCD) receiving at least one injection. Within 90 minutes of injection, systemic allergic reactions occurred in 5/180 (3%) PSAR/MCD participants given Pfizer-BioNTech (vs 0/133 [0%] Comparison Group; p=0.063) and 2/173 (1%) PSAR/MCD participants given Moderna (vs 0/144 [0%] Comparison Group; p=0.27). Reactions were also reported >90 minutes and ≤48 hours only in PSAR/MCD. Among PSAR/MCD participants, reaction rates to vaccine within 90-minutes and 48-hours were similar to placebo. Extensive laboratory studies did not identify plausible reaction mechanisms.

CONCLUSIONS

Systemic allergic reactions based solely on clinical determination within 90-minutes or 48-hours of vaccination were only observed in PSAR/MCD but failure to achieve planned enrollment limited statistical precision. Reactions to placebo and failure to identify underlying immunologic mechanisms suggest non-allergic or non-immunologic causes.