Several voices express their suspicions that mast cell activation plays a role in both the acute and chronic phases of COVID 19 disease. While these immune cells get more attention for their ability to release histamine and thereby cause allergic symptoms, they play a more common role than most would suspect. With the predicted frequency of mast cell dysfunction in society mirroring the observed frequency of severe COVID disease and post COVID disease, some are asking whether mast cell hyper-activation plays a role in COVID 19 manifestations. The symptom similarity makes that even more suspicious.
As other articles on my website describe in more details, mast cells are early general responders for microbial invaders like bacteria and viruses. This places them in the innate system which simply says “good guy” or “bad guy” based on certain surface protein markers on the microbes. The innate system does not depend on antibodies which target specific microbes and ignores others. That is the job of the adaptive system, primarily B-cells that make the antibodies. The mast cells, after encountering something they consider “bad guy’ release chemical messengers which activate other processes and cells. They are best known for releasing histamine but also release or trigger the release of dozens of others. If overstimulated they can contribute to anaphylaxis or in COVID 19, possibly contribute to cytokine storm. (for a deeper understanding of the immune system, purchase my Immune Prepper course at SFMEmpower.com)
Those clinicians who have been working with mast cell activation disorder for decades, like Dr. Afrin in the primary cited paper, contend that we have several lines of evidence to connect mast cells and SARS- CoV2 pathology. Besides the frequency overlap mentioned earlier, the symptoms experienced by mast cell activation disorder patients parallels that of acute and chronic COVID 19: the episodic and sometimes severe fatigue, randomly triggered chemical sensitivities, palpitations, brain fog, migraines, postural orthostatic tachycardia syndrome, dizziness, and more.
Mechanistically, mast cells possess ACE-2 receptors on their surfaces which are the prime target for Sars CoV2 entry into cells. Further potential mechanistic links include enzymes like TMPRSS2 and chymase as well as immune messengers like transforming growth factor beta. First, a protein called Transmembrane serine protease 2 (TMPRSS2) which primes the viral spike protein is produced by mast cells (Theoharides, Conti 2020). Mast cells produce an enzyme called chymase which activates transforming growth factor beta and matrix metalloproteinase 9 which are involved in lung fibrosis (Chen 2017). Other articles I addressed in my recent long hauler videos (on Facebook page) indicate that several lines of research hint that transforming growth factor beta is involved in the heart and kidney disease of COVID 19.
After severe lung disease, if we take a look at the crime scene (the lungs), we will find large numbers of mast cells in the lung tissue (Junior 2020). The primary article by Afrin et al note that therapies effective for mast cell disease also help patients suffering from COVID 19.
With all these lines of evidence, we at least deserve some further research into both the links between mast cells and COVID 19 AND the therapies that might help both acute and post COVID disease. Until then, we are using mast cell stabilizers like quercetin, NAC, vitamin C, and more to treat both our acute and long hauler patients with success. Caring for patients in 2021 and beyond requires an understanding of the underlying science as well as willingness to apply what we know to our current patients to save and to restore healthier lives.
Afrin, Lawrence B et al. “Covid-19 hyperinflammation and post-Covid-19 illness may be rooted in mast cell activation syndrome.” International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases vol. 100 (2020): 327-332. doi:10.1016/j.ijid.2020.09.016
Chen H., Xu Y., Yang G., Zhang Q., Huang X., Yu L., Dong X. Mast cell chymase promotes hypertrophic scar fibroblast proliferation and collagen synthesis by activating TGF-β1/Smads signaling pathway. Exp. Med. 2017;14:4438–4442. doi: 10.3892/etm.2017.5082.
Conti, P et al. “Mast cells activated by SARS-CoV-2 release histamine which increases IL-1 levels causing cytokine storm and inflammatory reaction in COVID-19.” Journal of biological regulators and homeostatic agents vol. 34,5 (2020): 1629-1632. doi:10.23812/20-2EDIT
Hafezi, Bahareh et al. “Cytokine Storm Syndrome in SARS-CoV-2 Infections: A Functional Role of Mast Cells.” Cells vol. 10,7 1761. 12 Jul. 2021, doi:10.3390/cells10071761
Junior J.M., Miggiolaro A.S., Nagashima S., De Paula C.B.V., Baena C.P., Scharfstein J., DE NORONHA L. Mast cell degranulation in alveolar septa and SARS-COV-2: A pathogenic pathway linking interstitial edema to immunothrombosis. Front. Immunol. 2020;11:2369.
Theoharides, Theoharis C. “Potential association of mast cells with coronavirus disease 2019.” Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology vol. 126,3 (2021): 217-218. doi:10.1016/j.anai.2020.11.003
Theoharides T.C., Conti P. COVID-19 and Multisystem Inflammatory Syndrome, or is it Mast Cell Activation Syndrome? J. Biol. Regul. Homeost. Agents. 2020;34:1633–1636. doi: 10.23812/20-EDIT3.
Sanctuary Functional Medicine, under the direction of Dr Eric Potter, IFMCP MD, provides functional medicine services to Nashville, Middle Tennessee and beyond. We frequently treat patients from Kentucky, Alabama, Mississippi, Georgia, Ohio, Indiana, and more... offering the hope of healthier more abundant lives to those with chronic illness.