COVID-19 derives from infection with Coronavirus [severe acute respiratory syndrome (SARS)-CoV-2] and is associated with high morbidity and mortality due to release of a storm of pro-inflammatory cytokines and thrombogenic agents resulting in destruction of the lungs. Many reports indicate that a considerable number of patients who are positive for SARS-CoV-2 are asymptomatic or have mild symptoms. However, increasing evidence suggests that many such patients who either recovered from or had mild symptoms after COVID-19 exhibit diffuse, multiorgan, symptoms months after the infection. These symptoms include malaise, myalgias, chest tightness, brain fog and other neuropsychiatric symptoms that were originally reported in children and named Multisystem Inflammatory Syndrome (MIS-C). Now the US Center for Disease Control (CDC) announced the recognition of a similar condition in adults, named Multisystem Inflammatory Syndrome (MIS-A). The symptoms characterizing these conditions are very similar to those associated with Mast Cell Activation Syndrome (MCAS, US ICD-110 code D89.42-idiopathic mast cell activation syndrome). Hence, the possibility of MCAS should be evaluated in any patient with MIS and/or multisystem inflammatory symptoms. In either case, these syndromes should be addressed with liposomal formulation (in olive pomace oil) of the flavone luteolin (e.g. PureLut(R) or FibroProtek(R)) together with the antihistamine rupatadine, which also has anti-platelet activating factor (PAF) activity and inhibits mast cells that have been implicated in the pathogenesis of cytokine storms in COVID-19.