Figure 1.

Illustration of proposed model. Normal mast cells (MCs) react normally to SARS-CoV-2, participating in driving mild to moderate symptoms through the network of inflammatory cells, and returning to a quiescent state once the virus has been eradicated. Some of the MCs will be abnormal/dysfunctional and prone to constitutive and reactive hyperactivation if mast cell activation syndrome (MCAS) is present. If MCAS is undiagnosed and thus untreated, the abnormal MCs may react inappropriately and excessively to SARS-CoV-2, driving a hyperinflammatory state via excessive release of their mediators and excessive recruitment (also via their released mediators) of other inflammatory cells. If MCAS is diagnosed and treated, the abnormal MCs will be relatively controlled, diminishing their aberrant hyperreactivity to SARS-CoV-2. As major stressors (such as infections and hyperinflammation) can induce major escalations in baseline MC dysfunction in MCAS (likely via induction of additional mutations in the stem cells and multipotent progenitors at the root of the patient’s population of dysfunctional MCs), the abnormal MCs in MCAS will have potential to drive post-Covid inflammatory syndrome (with clinical specifics dependent on the mutational profiles in the individual patient’s MCs), but the severity of that syndrome may be mitigated by recognition/diagnosis of the patient’s MCAS and pharmacologic control of the patient’s dysfunctional MCs.