The newly created mRNA-based COVID-19 vaccines have the potential to cause anaphylaxis, which could be triggered by the vaccine’s polyethylene glycol (PEG).  For a study, researchers defined 2 cohorts of individuals: 1 pre-vaccination, which included 187 individuals with high-risk profiles for developing anaphylaxis, and the other post-vaccination, which included 87 individuals with suspected allergic reactions after receiving the COVID19 mRNA vaccine. After a negative skin test with an mRNA vaccine, a 2-step (10% -90%) immunization protocol was used. A basophil activation test (BAT) validated positive skin testing. About 87 possible adverse reactions (5 after the booster) were submitted to the division for further study among 604’267 doses of the vaccine: 18/87 (21%) had symptoms associated with anaphylaxis, 78/87 (90%) were female, and 47/87 (54%) had received the BNT162b2 mRNA vaccination. Vaccine skin tests were negative in 96% and 76% of the pre-and post-vaccination cohorts. A 2-step vaccine was tolerated in 232/236 (98%) of those who tested negative. During the 2-step challenge, 4 people had isolated asthmatic reactions. BAT consistently validated vaccine-positive skin tests, and ibrutinib decreased CD63 and CD203c expression, suggesting an IgE-dependent mechanism. Intradermal testing could detect SARS-Cov2 mRNA vaccination sensitization. In the post-vaccination cohort, significantly more people were sensitized to mRNA vaccinations. Following negative skin testing, a 2-step 10%-90% immunization procedure could be safely administered.