The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), Multisystem Inflammatory Syndrome in Children (MIS-C), Adults (MIS-A), Neonates (MIS-N), and some Vaccinees (MIS-V). These are all considered clinically distinct diseases; however, the MIS-X diseases have overlapping symptoms and treatments with Kawasaki Disease (KD). MIS-C, MIS-A, MIS-N, and KD occur with increased frequencies several weeks following increased numbers of COVID-19 and for KD other pathogens. The incidence rate for MIS-C, MIS-A, MIS-N, and KD are typically a factor of roughly 5,000 lower than COVID-19 and for KD other pathogens. In this podcast, Dr. Darrell Ricke advances the hypothesis that MIS-C, MIS-A, MIS-N, MIS-V, and KD all represent a novel type of antibody-dependent enhanced (ADE) diseases associated with hyperactivation of granulocytes or mast cells. Symptoms for these diseases overlap those of histamine intolerance (HIT) coupled with pathogen associated symptoms. This ADE model proposes that antibody titer levels higher than primary immune response levels can hyperactivate granulocytes or mast cells to release inflammatory molecules including histamine; MIS-X and KD disease symptoms onset when histamine levels exceed the individual’s tolerance level. The proposed ADE model purports that patient treatment with intravenous immunoglobulin (IVIG) is successful in treating the MIS-X disease because IVIG compete with pathogen antibodies for binding to Fc receptors on immune cells, thereby reducing the immune responses to the pathogen or vaccine protein. This model is further supported with the vaccine spike protein activating immune cells via envisioned Fc receptor binding. This ADE model proposes additional antihistamine and diamine oxidase (DAO) adjunctive treatments combined with current standard of care treatments for investigation.