Mast cell activation symptoms are prevalent in Long-COVID

doi:10.1016/j.ijid.2021.09.043

. 2021 Nov:112:217-226.

doi: 10.1016/j.ijid.2021.09.043. Epub 2021 Sep 23.

Mast cell activation symptoms are prevalent in Long-COVID

Leonard B Weinstock¹, Jill B Brook², Arthur S Walters³, Ashleigh Goris⁴, Lawrence B Afrin⁵, Gerhard J Molderings⁶

Affiliations

¹ Associate Professor of Clinical Medicine, Departments of Medicine, Missouri Baptist Medical Center and Washington University School of Medicine, President, Specialists in Gastroenterology, 11525 Olde Cabin Road, St. Louis, MO, USA 63141, TEL 314-997-4627, FAX 314-997-5086. Electronic address: lw@gidoctor.net.
² Biostatistics, Private Practice, 13285 Roundhill, Truckee, CA, USA 96161, TEL 626-375-6725. Electronic address: jillbrook@msn.com.
³ Professor of Neurology, Division of Sleep Medicine, Vanderbilt University School of Medicine, Medical Center North A-0118, 1161 21(st) Ave South, Nashville, TN, USA 37232-2551, TEL 615-322-0283, FAX 615- 936-5663. Electronic address: art.walters@vumc.org.
⁴ Manager, Infection Prevention & Control and Clinical Quality, Missouri Baptist Medical Center, Mailstop: 95, 3015 N. Ballas Road, St. Louis, MO, USA 63131, TEL 314-996-5421, FAX 314-996-5909. Electronic address: Ashleigh.goris@Mercy.Net.
⁵ Department of Mast Cell Studies, Hematology/Oncology, AIM Center for Personalized Medicine, Purchase, NY, USA 10577, TEL 914-730-7390, FAX 914-730-7391. Electronic address: drafrin@aimcenterpm.com.
⁶ Associate Professor of Pharmacology and Toxicology, Molecular Geneticist, Immunologist, Institute of Human Genetics, University Hospital Bonn, D53127 Bonn, Germany, TEL ++49 1623322001, FAX ++49 2225 9984911. Electronic address: molderings@uni-bonn.de.

PMID: 34563706
PMCID: PMC8459548
DOI: 10.1016/j.ijid.2021.09.043

Mast cell activation symptoms are prevalent in Long-COVID

Leonard B Weinstock et al. Int J Infect Dis. 2021 Nov.

. 2021 Nov:112:217-226.

doi: 10.1016/j.ijid.2021.09.043. Epub 2021 Sep 23.

Authors

Leonard B Weinstock¹, Jill B Brook², Arthur S Walters³, Ashleigh Goris⁴, Lawrence B Afrin⁵, Gerhard J Molderings⁶

Affiliations

¹ Associate Professor of Clinical Medicine, Departments of Medicine, Missouri Baptist Medical Center and Washington University School of Medicine, President, Specialists in Gastroenterology, 11525 Olde Cabin Road, St. Louis, MO, USA 63141, TEL 314-997-4627, FAX 314-997-5086. Electronic address: lw@gidoctor.net.
² Biostatistics, Private Practice, 13285 Roundhill, Truckee, CA, USA 96161, TEL 626-375-6725. Electronic address: jillbrook@msn.com.
³ Professor of Neurology, Division of Sleep Medicine, Vanderbilt University School of Medicine, Medical Center North A-0118, 1161 21(st) Ave South, Nashville, TN, USA 37232-2551, TEL 615-322-0283, FAX 615- 936-5663. Electronic address: art.walters@vumc.org.
⁴ Manager, Infection Prevention & Control and Clinical Quality, Missouri Baptist Medical Center, Mailstop: 95, 3015 N. Ballas Road, St. Louis, MO, USA 63131, TEL 314-996-5421, FAX 314-996-5909. Electronic address: Ashleigh.goris@Mercy.Net.
⁵ Department of Mast Cell Studies, Hematology/Oncology, AIM Center for Personalized Medicine, Purchase, NY, USA 10577, TEL 914-730-7390, FAX 914-730-7391. Electronic address: drafrin@aimcenterpm.com.
⁶ Associate Professor of Pharmacology and Toxicology, Molecular Geneticist, Immunologist, Institute of Human Genetics, University Hospital Bonn, D53127 Bonn, Germany, TEL ++49 1623322001, FAX ++49 2225 9984911. Electronic address: molderings@uni-bonn.de.

PMID: 34563706
PMCID: PMC8459548
DOI: 10.1016/j.ijid.2021.09.043

Abstract

Objectives: 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. We determined prevalence/severity of MCA symptoms in LC.

Methods: 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.

Results: There were 136 LC 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.

Conclusions: MCA symptoms were increased in LC and mimicked the symptoms and severity reported by patients who have MCAS. Increased activation of aberrant mast cells induced by SARS-CoV-2 infection by various mechanisms may underlie part of the pathophysiology of LC, possibly suggesting routes to effective therapy.

Keywords: COVID-19; Long-COVID; fatigue; mast cell activation.

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Figures

**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.

**Figure 4**
Changes in Long-COVID participants mean symptom severity scores before and after COVID-19 (all are statistically different; p<0.05).

See this image and copyright information in PMC

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References

1. Afrin L.B., Butterfield J.H., Raithel M., Molderings G.J. Often seen, rarely recognized: mast cell activation disease–a guide to diagnosis and therapeutic options. Review article. Ann Med. 2016;48:190–201. - PubMed
1. Afrin L.B., Cichocki F., Hoeschen A., Beckman K.B., Gupta K., Nguyen J., et al. Mast cell regulatory gene variants are common in mast cell activation syndrome. Blood. 2016;128(22):4878. doi: 10.1182/blood.V128.22.4878.4878. - DOI
1. Afrin L.B., Self S., Menk J., Lazarchick J. Characterization of mast cell activation syndrome. Am J Med Sci. 2017;353(3):207–215. doi: 10.1016/j.amjms.2016.12.013. Mar PMID: 28262205; PMCID: PMC5341697. - DOI - PMC - PubMed
1. Afrin L.B., Ackerley M.B., Bluestein L.S., Brewer J.H., Brook J.B., Buchanan A.D., et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl) 2020;8(2):137–152. doi: 10.1515/dx-2020-0005. PMID: 32324159. - DOI - PubMed
1. Afrin L.B., Weinstock L.B., Molderings G.J. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020;100:327–332. - PMC - PubMed

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[1] Afrin L.B., Butterfield J.H., Raithel M., Molderings G.J. Often seen, rarely recognized: mast cell activation disease–a guide to diagnosis and therapeutic options. Review article. Ann Med. 2016;48:190–201. - PubMed

[2] Afrin L.B., Butterfield J.H., Raithel M., Molderings G.J. Often seen, rarely recognized: mast cell activation disease–a guide to diagnosis and therapeutic options. Review article. Ann Med. 2016;48:190–201. - PubMed

[3] Afrin L.B., Cichocki F., Hoeschen A., Beckman K.B., Gupta K., Nguyen J., et al. Mast cell regulatory gene variants are common in mast cell activation syndrome. Blood. 2016;128(22):4878. doi: 10.1182/blood.V128.22.4878.4878. - DOI

[4] Afrin L.B., Cichocki F., Hoeschen A., Beckman K.B., Gupta K., Nguyen J., et al. Mast cell regulatory gene variants are common in mast cell activation syndrome. Blood. 2016;128(22):4878. doi: 10.1182/blood.V128.22.4878.4878. - DOI

[5] Afrin L.B., Self S., Menk J., Lazarchick J. Characterization of mast cell activation syndrome. Am J Med Sci. 2017;353(3):207–215. doi: 10.1016/j.amjms.2016.12.013. Mar PMID: 28262205; PMCID: PMC5341697. - DOI - PMC - PubMed

[6] Afrin L.B., Self S., Menk J., Lazarchick J. Characterization of mast cell activation syndrome. Am J Med Sci. 2017;353(3):207–215. doi: 10.1016/j.amjms.2016.12.013. Mar PMID: 28262205; PMCID: PMC5341697. - DOI - PMC - PubMed

[7] Afrin L.B., Ackerley M.B., Bluestein L.S., Brewer J.H., Brook J.B., Buchanan A.D., et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl) 2020;8(2):137–152. doi: 10.1515/dx-2020-0005. PMID: 32324159. - DOI - PubMed

[8] Afrin L.B., Ackerley M.B., Bluestein L.S., Brewer J.H., Brook J.B., Buchanan A.D., et al. Diagnosis of mast cell activation syndrome: a global "consensus-2". Diagnosis (Berl) 2020;8(2):137–152. doi: 10.1515/dx-2020-0005. PMID: 32324159. - DOI - PubMed

[9] Afrin L.B., Weinstock L.B., Molderings G.J. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020;100:327–332. - PMC - PubMed

[10] Afrin L.B., Weinstock L.B., Molderings G.J. Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome. Int J Infect Dis. 2020;100:327–332. - PMC - PubMed

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Mast cell activation symptoms are prevalent in Long-COVID

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Mast cell activation symptoms are prevalent in Long-COVID

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