Etiology model for many vaccination adverse reactions, including SARS-CoV-2 spike vaccines

Abstract

<abstract><sec> <title>Objective</title> <p>Vaccinated individuals (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. The number of vaccine adverse reactions is higher for SARS-CoV-2 spike vaccines than all other vaccines. Can data analysis of vaccine adverse reactions responses provide etiology insights for high reactogenicity vaccines?</p> </sec><sec> <title>Methods</title> <p>The Vaccine Adverse Event Reporting System (VAERS) database was data mined for all vaccine adverse events data by vaccine, age, gender, dose, and day of onset post vaccination. Results for vaccines with the highest number of adverse events were compared.</p> </sec><sec> <title>Results</title> <p>For vaccines and adverse events with the highest numbers of reports, the day of onset approximates a power of two decay pattern for the first three days. The consistency of this pattern for multiple unrelated vaccines narrows possible etiology mechanisms. Many of these adverse event symptoms overlap symptoms associated with elevated histamine levels. Herein, innate immune responses and specifically elevated histamine levels are proposed to be causative for the majority of these adverse events. 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 causing 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 specific 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.</p> </sec><sec> <title>Conclusions</title> <p>The reported onset occurrences of the majority of reported adverse events are consistent with the likely etiology of innate immune responses to vaccinations for vaccines with higher reactogenicity levels. Herein, the hypothesis is proposed that the majority of these adverse events result from a histamine surge that temporarily exceeds the vaccinee's tolerance level.</p> </sec></abstract>