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Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome
Lawrence B Afrin1, Leonard B Weinstock2, Gerhard J Molderings3
1Department of Mast Cell Studies, AIM Center for Personalized Medicine, Purchase, New York, USA.
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.
Insights
Mast cell activation syndrome (MCAS) may explain severe COVID-19 and long COVID. Dysfunctional mast cells, not normal ones, might drive hyperinflammation in severe COVID-19 patients.
Area of Science:
- Immunology
- Infectious Diseases
- Allergy and Immunology
Background:
- Severe COVID-19 affects 20% of patients, with unclear causes.
- Mast cell activation syndrome (MCAS) is a chronic disorder affecting an estimated 17% of the population.
- SARS-CoV-2 activates mast cells, suggesting a link to COVID-19 severity.
Purpose of the Study:
- To propose a novel conjecture linking MCAS to severe acute COVID-19 and chronic post-COVID-19 conditions.
- To explore the role of mast cell dysfunction in COVID-19 pathogenesis.
Main Methods:
- Comparison of COVID-19 illness observations in patients with and without MCAS.
- Leveraging extensive clinical experience with MCAS.
Main Results:
- MCAS prevalence mirrors severe COVID-19 case rates.
- COVID-19 hyperinflammation patterns align with mast cell activation.
- Preliminary observations suggest MC-targeting drugs benefit COVID-19 patients.
- No treated MCAS patients in the study experienced severe COVID-19 or mortality.
Conclusions:
- Severe COVID-19 hyperinflammation may stem from atypical mast cell responses in MCAS.
- This theory suggests dysfunctional mast cells, not normal ones, drive severe COVID-19.
- The findings have potential therapeutic and prognostic implications for COVID-19 and MCAS.
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