Mast Cell Activation Syndrome and Long Covid

Most of us who have been diagnosed with Post-COVID Postural Orthostatic Tachycardia Syndrome (POTS) and, if we are lucky enough to have been seen by a POTS specialist, have been told that there is a close link between Mast Cell Activation Syndrome/ Symptoms, POTS and Long Covid. Some of us have been started on anti-histamines such as cetirizine or fexofenadine and on the H2 blocker - Famotidine. Recently some have been lucky enough to be started on Ketotifen, a mast cell stabiliser,as well and are reporting great benefits.

And there are those who have reported sudden aggressive allergies to everyday items - this is also a feature of MCAS.

Please read my posts on MCAS for further information on this condition - details in the reference at the end of this blog.

Dr Afrin, a MCAS specialist, has released a new paper "Mast cell activation symptoms are prevalent in Long-COVID" in the International Journal of Infectious Diseases


  • Mast cell activation symptoms (MCAS) were increased in Long-COVID patients

  • Long-COVID patients had similar severity of numerous MCAS symptoms

  • Aberrant mast cells induced by SARS-CoV-2 infection is the likely triggering factor

  • Mast Cell-directed therapy could help treat Long-COVID patients

Why did they do it? Hyper-inflammation caused by COVID-19 may be mediated by mast cell activation (MCA) which has also been hypothesized to cause Long COVID (LC) symptoms. They wanted to determine the prevalence and severity of MCA symptoms in LC.

What did they do?

Adults in LC-focused Facebook support groups were recruited for online assessment of symptoms before and after COVID-19. Questions included presence and severity of known MCA and LC symptoms and validated assessments of fatigue and quality of life. General population controls and mast cell activation syndrome (MCAS) patients were recruited for comparison if they were ≥18 years of age and never had overt COVID-19 symptoms.

Symptoms found:

What did they find?

There were 136 Long COVID subjects (89.7% females, age 46.9 ±12.9 years), 136 controls (65.4% females, age 49.2 ±15.5), and 80 MCAS patients (85.0% females, age 47.7 ±16.4).

  • Pre-COVID-19 LC subjects and controls had virtually identical MCA symptom and severity analysis.

  • Post-COVID-19 LC subjects and MCAS patients prior to treatment had virtually identical MCA symptom and severity analysis.

This was based on MCMRS Scores - the latest version of the mast cell mediator release syndrome (MCMRS) score was employed, which includes symptoms and severity scores of symptoms seen in MCA disorders.

Figure 1. Mean mast cell mediator release syndrome scores for each group, with whiskers showing 95% confidence intervals.

Figure 2. Mean mast cell mediator release syndrome cumulative severity for each group, with whiskers showing 95% confidence intervals.

Figure 3. Spider web plots of mean mast cell mediator release syndrome scores.

What they conclude? 1. MCA symptoms were increased in Long-COVID

2. The MCA symptoms mimicked the symptoms and severity reported by patients who have MCAS.

3. Increased activation of aberrant mast cells induced by SARS-CoV-2 infection by various mechanisms may underlie part of the pathophysiology of Long-COVID, possibly suggesting routes to effective therapy.

What were the potential limitations of the study?

  • Gender recruitment imbalance. LC females outnumbered LC males. This is likely due to the makeup of the LC Facebook group and/or gender preference for recruitment.

  • Subjects were gathered from social media support groups. These groups are largely self-selected and do not constitute a randomly selected population and may not necessarily represent the general population of patients who have LC. Subjects who join a medical support group might be more ill than other patients.

  • The fact that the MCAS patients were diagnosed at a gastroenterology clinic that subspecializes in MCAS could have biased the comparison group by having increased severity of gastrointestinal symptoms.

  • Another potential problem is that the LC group completed their pre-COVID-19 questionnaire by recall, and thus this part of the study was retrospective. This was a limitation of the study design, yet the spider symptom/severity plots at baseline were remarkably similar to the general population control group, likely negating this issue.


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