Evaluation of association of anti-PEG antibodies with anaphylaxis after mRNA COVID-19 vaccination.

Background: The mechanism for anaphylaxis following mRNA COVID-19 vaccination has been widely debated; understanding this serious adverse event is important for future vaccines of similar design. A mechanism proposed is type I hypersensitivity (i.e., IgE-mediated mast cell degranulation) to polyethylene glycol (PEG). Using an assay that, uniquely, had been previously assessed in patients with anaphylaxis to PEG, our objective was to compare anti-PEG IgE in serum from mRNA COVID-19 vaccine anaphylaxis case-patients and persons vaccinated without allergic reactions. Secondarily, we compared anti-PEG IgG and IgM to assess alternative mechanisms.
Methods: Selected anaphylaxis case-patients reported to U.S. Vaccine Adverse Event Reporting System December 14, 2020-March 25, 2021 were invited to provide a serum sample. mRNA COVID-19 vaccine study participants with residual serum and no allergic reaction post-vaccination ("controls") were frequency matched to cases 3:1 on vaccine and dose number, sex and 10-year age category. Anti-PEG IgE was measured using a dual cytometric bead assay (DCBA). Anti-PEG IgG and IgM were measured using two different assays: DCBA and a PEGylated-polystyrene bead assay. Laboratorians were blinded to case/control status.
Results: All 20 case-patients were women; 17 had anaphylaxis after dose 1, 3 after dose 2. Thirteen (65 %) were hospitalized and 7 (35 %) were intubated. Time from vaccination to serum collection was longer for case-patients vs controls (post-dose 1: median 105 vs 21 days). Among Moderna recipients, anti-PEG IgE was detected in 1 of 10 (10 %) case-patients vs 8 of 30 (27 %) controls (p = 0.40); among Pfizer-BioNTech recipients, it was detected in 0 of 10 case-patients (0 %) vs 1 of 30 (3 %) controls (p >n 0.99). Anti-PEG IgE quantitative signals followed this same pattern. Neither anti-PEG IgG nor IgM was associated with case status with both assay formats.
Conclusion: Our results support that anti-PEG IgE is not a predominant mechanism for anaphylaxis post-mRNA COVID-19 vaccination.
Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Mary A Staat reports a relationship with Pfizer that includes: funding grants. Mary A Staat reports a relationship with Merck & Co Inc that includes: funding grants. Mary A Staat reports a relationship with UpToDate that includes: consulting or advisory. Donna S. Hummell reports a relationship with Merck & Co Inc that includes: consulting or advisory. Kathryn M. Edwards reports a relationship with Bionet that includes: consulting or advisory. Kathryn M. Edwards reports a relationship with IBM that includes: consulting or advisory. Kathryn M. Edwards reports a relationship with Member Data that includes: consulting or advisory. Kathryn M. Edwards reports a relationship with Sanofi, X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roache, Novavax, Brighton Collaboration that includes: consulting or advisory. UpToDate fees for Mary A. Stadt were classified as royalties that are unrelated to this work. Consultative work by Kathryn M. Edwards for X-4 Pharma, Seqirus, Moderna, Pfizer, Merck, Roche, Novavax, Brighton Collaboration was serving on Safety and Monitoring Boards. Consultative work by Donna S. Hummel for Merck was for eDMC monitoring for clinical trial.
(Published by Elsevier Ltd.)