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.

Do basophil activation tests help elucidate allergic reactions to the ingredients in COVID‐19 vaccines?

“… 32 Wortmannin experiments also confirmed that basophil activation by PEG or BNT‐vaccine was mediated by IgE. 28 Some authors have claimed that a non‐IgE‐mediated mechanism is the cause of basophil activation, because IgE against PEG could not be found in the serum. 10 , 28 The lack of detection could be due to methodological problems in these assays, because a new dual cytometric bead assay (using PEGylated products) was able to demonstrate that samples of patients with PEG‐associated anaphylaxis were clearly positive for anti‐PEG‐IgE.…”

“… 34 Experiments with the BAT showing a decrease in BNT‐vaccine‐induced basophil activation by preincubation with wortmannin might pose an argument for an IgE‐mediated immune response to SARS‐CoV‐2 spike proteins in patients with a previous SARS‐CoV‐2 infection. 28 BATs with spike peptides showed a slightly higher activation compared to baseline (below the cut‐off) in some patients with previous SARS‐CoV‐2 infection, which could be a hint for such a mechanism. 30 On the other hand, PEGylated compounds have the role of a solubilizer during the transition of the particles into the intracellular cytosol due to their hygroscopic properties, 35 which might influence unspecific detection or upregulation of surface markers on basophils in certain individuals.…”

“… 26 In one study with BNT‐vaccine, the results in patients supposed to be allergic were expressed in stimulation indices (SI) with values of 2.88, 3.1, 3.19 and 4.79. 28 …”

“… 5 The best concentration of the whole BNT‐vaccine giving positive results in the BAT was around 10 µg/ml tozinameran. 8 , 26 , 27 , 28 Dose‐response curves should include this concentration, though lower and higher concentrations can be successfully used.…”

“…ROC curves were performed in one study with PEG 2000 and BNT‐vaccine but were based on a very low number of positive results. 28 …”