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doi: 10.1016/j.ijid.2020.09.016. Epub 2020 Sep 10.

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

Affiliations

  • PMID: 32920235
  • PMCID: PMC7529115
  • DOI: 10.1016/j.ijid.2020.09.016

Free PMC article

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

Lawrence B Afrin  et al. Int J Infect Dis. 2020 Nov .

Free PMC article

Abstract

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.

Figures

Figure 1
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.

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Dr Afrin Mast Cell Diet

Source: https://pubmed.ncbi.nlm.nih.gov/32920235/

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