LAUSR

Objectives One-fifth of Covid-19 patients suffer a severely symptomatic, hyperinflammatory course, but specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Though only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes and estimated prevalence of 17%. We describe a novel conjecture explaining how MCAS might cause propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses. Methods Observations of Covid-19 illness in patients with/without MCAS, set against our extensive clinical experience with MCAS. Results The prevalence of MCAS is concordant with the prevalence of severe cases within the Covid-19-infected population. Much of Covid-19’s hyperinflammation is concordant with manners of inflammation which MC activation can drive. Drugs with activity against MCs or their mediators have been preliminarily observed helpful in Covid-19 patients. None of our treated MCAS patients who have endured Covid-19 infection have suffered severe courses of the infection, let alone mortality. Conclusions Hyperinflammatory cytokine storms in many severely symptomatic Covid-19 patients may be rooted in aberrant response to SARS-CoV-2 by the dysfunctional MCs of MCAS rather than normal response by normal MCs. If provable, our conjecture has significant therapeutic and prognostic implications.