BackgroundThe newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy or with a suspected allergic reaction after the first dose remains to be defined.MethodsIn this real-life study, we defined two cohorts of individuals: one pre-vaccination including 187 individuals with high-risk profiles for developing anaphylaxis and a second post-vaccination including 87 individuals with suspected allergic reactions after the COVID-19 mRNA vaccine. Upon negative skin test with an mRNA vaccine, a two-step (10–90%) vaccination protocol was performed. Positive skin tests were confirmed with the basophil activation test (BAT).ResultsAmong 604,267 doses of vaccine, 87 suspected allergic reactions (5 after the booster) were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% of the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced isolated asthmatic reactions during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism.ConclusionSensitization to SARS-CoV-2 mRNA vaccines can be detected with intradermal testing. Significantly more individuals were sensitized to mRNA vaccines in the post-vaccination cohort. A two-step 10–90%-vaccination protocol can be safely administered upon negative skin testing.

Background: The newly developed mRNA-based COVID-19 vaccines can provoke anaphylaxis, possibly induced by polyethylene glycol (PEG) contained in the vaccine. The management of persons with a history of PEG allergy, or with an allergic-like reaction after the first dose remains to be defined.  Methods: We studied two cohorts of individuals: one pre-vaccination, the second post-vaccination. Skin testing was performed with COVID-19 mRNA vaccines. Upon negative skin test, a two-step (10%-90%) vaccination protocol was performed. Positive skin tests were confirmed with basophil activation tests (BAT). Vaccine-sensitized patients were offered a five-step induction protocol. Results: We identified 187 patients with high-risk profiles for developing anaphylaxis. In parallel, among 385’926 doses of vaccine, 87 allergic-like reactions were reported to our division for further investigations: 18/87 (21%) were consistent with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) received the BNT162b2 mRNA vaccine. Vaccine skin tests were negative in 96% and 76% in the pre- and post-vaccination cohorts, respectively. A two-step vaccination was tolerated in 232/236 (98%) of individuals with negative tests. Four individuals experienced acute asthma exacerbation during the two-step challenge. Vaccine-positive skin tests were consistently confirmed by BAT; CD63 and CD203c expression was selectively inhibited with ibrutinib, suggesting an IgE-dependent mechanism. Finally, 13 sensitized patients were successfully vaccinated with a five-step vaccination protocol. Conclusion: A two-step 10%-90%-vaccination protocol can be safely administered upon negative skin testing. Yet, it should be delayed in individuals with poorly controlled asthma. Importantly, mRNA vaccine sensitized individuals may receive a five-step vaccination protocol.