Arguing against an IgE-mediated mechanism is the fact that the majority of anaphylactic reactions occurred at the first administration [13], the majority of cases with previous anaphylaxis to an mRNA-COVID-19 vaccine tolerated re-administration of an mRNA-COVID-19 vaccine under surveillance [48], and in a well-studied case series of 22 individuals with allergic reactions to an mRNA-COVID-19 vaccine, no PEG-specific or polysorbate 80-specific IgE was detectable, but PEG-specific IgG was detectable, suggesting a non-IgE-mediated mechanism such as CARPA [49]. This evidence concerns the gene IGHE and anaphylaxis.