Elevated Histamine Etiology Model for Most Major Vaccine Associated Adverse Events including SARS-CoV-2 Spike Vaccines

Abstract Vaccinees experience no adverse events, mild adverse events, multiple adverse events, or serious adverse events post vaccination. Many of these vaccine adverse events occur with different vaccines with different occurrence frequencies. Many of these adverse events are generally considered as associated with immune responses to the active vaccine components (antigens) and/or to possibly one or more of the vaccine excipients. Most of these vaccine adverse events are self-limiting and resolve within days. Many of these adverse events symptoms overlap symptoms associated with elevated histamine levels. Based on these observations, the hypothesis that the majority of vaccine associated reactogenicity adverse events are caused by temporal histamine intolerance in vaccinees is proposed. This hypothesis is based on a model of innate immune responses releasing a surge of inflammatory molecules including histamine; this surge is hypothesized to exceed the normal histamine tolerance level for vaccinees with reactogenicity adverse events. Further, these symptoms resolve as histamine levels fall below the vaccinee’s tolerance threshold. This model can be evaluated by the detection of elevated histamine levels in vaccinees corresponding to timing of symptoms onset. If confirmed, a direct consequence of this model predicts that some antihistamine treatments, mast cell stabilizers, and possibly diamine oxidase enzyme may reduce the incidence or severity of adverse events experienced by vaccinees post vaccinations for most or all high reactogenicity vaccines including coronavirus disease 2019 (COVID-19) Spike vaccines.