The value of the basophil activation test in the evaluation of patients reporting allergic reactions to the BNT162b2 mRNA COVID-19 vaccine

Abstract

Background: mRNA-based COVID-19 vaccines have been reported to induce hypersensitivity reactions (HSR) in a small number of individuals. We aimed to evaluate the real-world incidence of the BNT162b2 mRNA COVID-19 vaccine HSR and to determine the value of the basophil activation test (BAT) in the allergological workup of patients reporting these reactions.

Methods: We prospectively enrolled patients with a clinical history indicative of HSR to the BNT162b2 mRNA COVID-19 vaccine. The allergological workup included skin testing (STs) and BAT with polyethylene glycol (PEG) and the vaccine. In those with negative allergy assessments, the administration of the second dose of the BNT162b2 mRNA COVID-19 vaccine was offered.

Results: Seventeen adults were included. Eleven cases (64.7%) tested negative in the allergological workup and tolerated the re-administration of the second dose of the vaccine and considered non-allergic. Six cases (35.3%) were considered allergic and classified into three groups: 2 subjects displayed positive STs and/or BAT to PEG (Group A), two individuals displayed positive BAT to the vaccine (Group B), and in 2 patients with moderate or severe reactions, the culprit was not identified, tested negative to STs and BAT to both PEG and vaccine (Group C). We further evaluated the value of BAT when the results were positive to the vaccine and negative to PEG by performing BAT in controls groups, finding positive BAT results in 50% of controls, all of them recovered from COVID-19 infection. In contrast, BAT was negative in patients who had not suffered from COVID-19 disease.

Conclusions: BAT can be used as a potential diagnostic tool for confirming allergy to PEG excipient but not to the vaccine as a positive result in BAT may indicate a past COVID-19 infection instead of an allergy.

Keywords: BNT162b2; COVID-19; allergic reactions; basophil activation test; vaccines.

FIGURE 1

Flowchart for the distribution of study participants

FIGURE 2

Effect of vaccine at 10 and 1 µg/ml on stimulation index (SI) for activation marker CD 63 from patients and different controls groups. Group B: STs and or BAT positive to the vaccine. Group C‐NV: Controls COVID‐19 recovered, not vaccinated. Group C‐V: Controls COVID‐19 recovered, vaccinated with BNT162b2 without allergic reactions. Group NC‐NV: Control not suffered from COVID‐19 and not vaccinated. Group NC‐V: Control not suffered from COVID‐19 and vaccinated with BNT162b2 without allergic reaction

FIGURE 3

Effect of PEG at 100 µg/ml and vaccine at 10 and 1 µg/ml and effect of combination for each condition with wortmannin at 1 µM on stimulation index (SI) for activation marker CD 63 for group A and B of patients. Group A: STs and or BAT positive to PEG. Group B: BAT positive to the vaccine

FIGURE 4

Effect of vaccine at 10 and 1 µg/ml and effect of combination for each condition with wortmannin at 1 µM on stimulation index (SI) for activation marker CD 63 for both controls group COVID‐19 recovered. Group C‐NV: Controls COVID‐19 recovered, not vaccinated. Group C‐V: Controls COVID‐19 recovered, vaccinated with BNT162b2

FIGURE 5

(A) Effect of PEG at 100 µg/ml and vaccine at 10 and 1 µg/ml at different times after the first and the second dose vaccine administration on stimulation index (SI) for activation marker CD 63. (B) Effect of PEG at 100 µg/ml and vaccine at 10 and 1 µg/ml on stimulation index (SI) for activation marker CD 63 from the same patients at two different times after the first and the second dose vaccine administration

FIGURE 6

Proposed algorithm for the management of patients with reactions to the BNT162b2 vaccine