Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome

Int J Infect Dis. 2020 Nov:100:327-332. doi: 10.1016/j.ijid.2020.09.016. Epub 2020 Sep 10.


Objectives: One-fifth of Covid-19 patients suffer a severe course of Covid-19 infection; however, the specific causes remain unclear. Mast cells (MCs) are activated by SARS-CoV-2. Although only recently recognized, MC activation syndrome (MCAS), usually due to acquired MC clonality, is a chronic multisystem disorder with inflammatory and allergic themes, and an estimated prevalence of 17%. This paper describes a novel conjecture explaining how MCAS might cause a propensity for severe acute Covid-19 infection and chronic post-Covid-19 illnesses.

Methods: Observations of Covid-19 illness in patients with/without MCAS were compared with extensive clinical experience with MCAS.

Results: The prevalence of MCAS is similar to that 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 preliminarily been observed to be helpful in Covid-19 patients. None of the authors' treated MCAS patients with Covid-19 suffered severe infection, let alone mortality.

Conclusions: Hyperinflammatory cytokine storms in many severely symptomatic Covid-19 patients may be rooted in an atypical response to SARS-CoV-2 by the dysfunctional MCs of MCAS rather than a normal response by normal MCs. If proven, this theory has significant therapeutic and prognostic implications.

Keywords: Covid-19; Mast cell activation disease; Mast cell activation syndrome; Medical hypothesis; SARS-CoV-2.

MeSH terms

  • COVID-19 / complications*
  • COVID-19 / immunology
  • Humans
  • Inflammation / immunology
  • Mast Cells / immunology
  • Mastocytosis / drug therapy
  • Mastocytosis / epidemiology
  • Mastocytosis / etiology*
  • Pandemics
  • SARS-CoV-2