Early results of an in vivo and in vitro allergy testing protocol for COVID-19 vaccinations

ABSTRACT

Introduction: Mechanisms underlying allergic reactions to the new BNT162b2 (Pfizer) and AZD1222 (AstraZeneca) COVID-19 vaccinations are poorly understood. Polyethylene glycol (PEG) is implicated for BNT162b2;and polysorbate 80 (PS80) and disodium edetate (EDTA) for AZD1222. Methods: Patients referred to our service were investigated with standardised vaccine skin-prick testing (SPT) and intradermal testing (IDT) protocols. Basophil activation testing (BAT) was performed in patients with history highly suggestive of excipient or vaccine allergy. Results: Reason for referral was suspected excipient allergy in 16/23 (70%), previous other vaccine reaction in 4/23 (17%), and reaction to the BNT162b2 vaccine in 3/23 (13%). In patients with suspected excipient allergy, SPT was only positive in 1/16 (6%). In 12/16 patients with suspected PEG allergy, IDT and BAT were positive in 5 (42%) for the BNT162b2 vaccine but not PEG. 3/5 have subsequently undergone successful vaccination with AZD1222, while 1/5 had cross-reactivity with AZD1222 on BAT and has not been vaccinated. 2/16 patients with suspected PS80 allergy were negative on SPT, IDT, and BAT, and have undergone successful AZD1222 vaccination. In the 2/16 patients with EDTA allergy IDT was positive to EDTA but neither vaccine, correlating with BAT. 1 has been successfully vaccinated with the EDTA-containing AZD1222 vaccine. 2 patients (1 reaction to BNT162b2, 1 other vaccine reaction) developed systemic reactions during testing without tryptase elevation. Both were associated with local flare response to the BNT162b2 vaccine, both have undergone successful vaccination with the AZD1222 vaccine. All other patients with negative SPT, IDT, and BAT results have subsequently tolerated vaccination. Conclusion: Most patients can be successfully vaccinated with available COVID-19 vaccines. SPT has low sensitivity and a combined protocol of SPT, IDT, and BAT provides confidence in allergy delabelling. Not all excipient allergies correlate to vaccination allergy and BAT provides a powerful diagnostic tool in these cases.