Risk Factors Associated with Treated Acute-Onset Hypersensitivity Reactions after COVID-19 Mrna Vaccinations

COVID-19 mRNA vaccine-associated acute-onset hypersensitivity reactions are widely reported, but population-based incidence data on treated reactions and tolerance of subsequent doses is lacking. All Kaiser Permanente Southern California members who received COVID-19 mRNA vaccinations between 12-15-2020 and 3-11-2021 at a KPSC facility and had a treated acute-onset hypersensitivity event within 6 hours were identified. Anaphylaxis was defined as objective findings meeting WAO 2020 criteria. There were total of 606,273 COVID-19 mRNA vaccines (267,209 Pfizer-BioNTech(P), 339,064 Moderna(M)) administered to 391,022 unique individuals who were 59.18% female, average age 64 years with 1 drug “allergy”. Of 372,745 first doses administered (162,508P; 210,237M), 104 (0.027%) individuals were treated for reactions (36P; 68M); 89 (86%) females, average age 53 years with 2 drug “allergies”. Of 233,528 second doses administered, (104,701P; 128,827M), 32 (0.0137%) individuals were treated (11P; 21M); 30 (94%) females, average age 57 years and 2 drug “allergies”. There were 31 (26-1st dose) reactions treated with epinephrine, 119 (90-1st dose) with antihistamines, and 40 (31-1st dose) with corticosteroids. Only 2 (0.0003%) were confirmed anaphylaxis after chart review. Of 104 with first-dose treated reactions, 29 (28%) received a second dose, of whom only 6 (21%) were re-treated. Treated acute-onset hypersensitivity reactions were more common with 1st COVID-19 mRNA Moderna vaccinations in younger females with > 2 listed drug “allergies”. Our confirmed anaphylaxis rate was 3.3 per one million doses administered. Most treated reactions are likely not immunologically-mediated, because no booster effect was seen, or from direct nanoparticle-induced complement activation, because second-dose reactions were rarer.