Diagnostic accuracy of vaccine and vaccine excipient testing in the setting of allergic reactions to COVID‐19 vaccines: A systematic review and meta‐analysis

For persons with immediate allergic reactions to mRNA COVID-19 vaccines, skin testing (ST) to the vaccine/excipients (polyethylene glycol[PEG] and polysorbate 80 [PS]) has been recommended, but has unknown accuracy. To assess vaccine/excipient ST accuracy in predicting all-severity immediate allergic reactions upon re-vaccination, systematic review was performed searching Medline, EMBASE, Web of Science, and the WHO global coronavirus database (inception-Oct 4, 2021) for studies addressing immediate (≤4 h post-vaccination) all-severity allergic reactions to 2nd mRNA COVID-19 vaccination in persons with 1st dose immediate allergic reactions. Cases evaluating delayed reactions, change of vaccine platform, or revaccination without vaccine/excipient ST were excluded. Meta-analysis of diagnostic testing accuracy was performed using Bayesian methods. The GRADE approach evaluated certainty of the evidence, and QUADAS-2 assessed risk of bias. Among 20 studies of mRNA COVID-19 first dose vaccine reactions, 317 individuals underwent 578 ST to any one or combination of vaccine, PEG, or PS, and were re-vaccinated with the same vaccine. Test sensitivity for either mRNA vaccine was 0.2 (95%CrI 0.01-0.52) and specificity 0.97 (95%CrI 0.9-1). PEG test sensitivity was 0.02 (95%CrI 0.00-0.07) and specificity 0.99 (95%CrI 0.96-1). PS test sensitivity was 0.03 (95%CrI 0.00-0.0.11) and specificity 0.97 (95%CrI 0.91-1). Combined for use of any of the 3 testing agents, sensitivity was 0.03 (95%CrI 0.00-0.08) and specificity was 0.98 (95%CrI 0.95-1.00). Certainty of evidence was moderate. ST has low sensitivity but high specificity in predicting all-severity repeat immediate allergic reactions to the same agent, among persons with 1st dose immediate allergic reactions to mRNA COVID-19 vaccines. mRNA COVID-19 vaccine or excipient ST has limited risk assessment utility.