Spike protein and mast cell activation

Perhaps one of the most puzzling aspects of COVID-19 lies in its dichotomy between asymptomatic/mild cases and the unusual (for a viral illness) hyper-inflammatory symptomatology of severe cases. 

Here, I would like to draw the connections between a triad of players that may explain the puzzle: the Spike protein, mast cells, and vitamin D.

Mast cells are granulocytes that discharge inflammatory substances (such as histamine, leukotrienes, prostaglandins, and cytokines) when triggered by specific stimuli. Mast cells are present in most tissues, including the lung, the gut, and the brain. They were originally recognized for their capacity to kill parasites with the toxic contents of their granules. However, a dysregulated degranulation of mast cells can result in allergy or hyper-inflammation.

Mast cells have been suspected to play a role in the severity of COVID-19. For example, back in November of 2020 a group of doctors and mast cell researchers postulated the following: “Much of Covid-19's hyperinflammation is concordant with manners of inflammation which MC [mast cell] 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 [mast cell activation syndrome] patients with Covid-19 suffered severe infection, let alone mortality. 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.” LINK

An experimental confirmation of their hunch about mast cells came recently. In December of 2021, Wu et al. published a study titled SARS-CoV-2-triggered mast cell rapid degranulation induces alveolar epithelial inflammation and lung injury. The title is self-explanatory. Interestingly, these researchers could recapitulate the effects of the virus on mast cell degranulation with just the Spike protein binding to the ACE2 receptor on mast cells. This makes their findings relevant not only to the impact of COVID infection, but also to the impact of COVID vaccines, which make the body produce the Spike protein for undetermined duration of time.  

In other words, viruses and vaccines that are capable of triggering mast cells (via ACE2) are putting some people at risk of severe outcomes. This is especially the case for people, whose mast cells are already destabilized due to environmental exposures, chronic inflammation or pre-existing conditions. 

A 2017 study found that mast cells activate spontaneously in a vitamin D-deficient environment. In light of this finding, it shouldn’t be surprising that vitamin D levels are inversely correlated with COVID severity, if indeed mast cells are driving it. And pre-existing chronic conditions are often accompanied by low vitamin D levels. In obese patients with diabetes, masts cells exhibit more inflammatory features and are increased in numbers. Glyphosate exposure also increases the number of mast cells in the GI tract.

Maintaining adequate plasma levels of Vitamin D is not simply a matter of dietary intake and sun exposure, but also depends upon the reduction in pollutant exposure and a healthy microbiome.  

Urinary levels of pollutants like BPA and phthalates inversely correlate with vitamin D levels in humans, with animal studies needed to establish causation. An experimental oral exposure of mice to low doses of cadmium (a heavy metal) was shown to induce vitamin D degradation by their gut microbiome. 

A study on gut microbiome in older men found that higher levels of active vitamin D are associated with presence of butyrate-producing (beneficial) bacteria.

Inflammatory endotoxin LPS, produced by certain strains of gut bacteria, can be responsible for driving chronic inflammation via endotoxemia (increased presence of LPS in the bloodstream). And chronic inflammation depletes vitamin D. The link between LPS and vitamin D degradation has been established in this study, by showing that LPS upregulates vitamin D-metabolizing enzymes, CYP27B1 and CYP24A1, in white blood cells.

Stabilization of mast cells requires maintaining a healthy gut barrier to prevent LPS leakage into the bloodstream and subsequent vitamin D degradation. But dysregulated mast cells themselves can pose a challenge to healing the gut as they contribute to the gut barrier dysfunction, potentially fueling their own destabilization.

In addition, mast cells can degranulate when exposed to an endocrine-disrupting herbicide atrazine and power-frequency EMFs. Mercury (including the vaccine preservative thimerosal) can also result in the release of inflammatory mediators from mast cells. And let’s not forget that psychological stress exacerbates mast cells via stress hormones and neuropeptides.

Healing long-COVID or COVID vaccine injury, as well as preparing to handle COVID exposure uneventfully should include mast cell care. While improving one’s vitamin D status and gut microbiome diversity is a must for mast cell stabilization, there are also some food substances known to mitigate their activation. Among them are amino acids arginine and glutamine, polyphenols quercetin and luteolin, and cinnamon extract.

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Disclaimer: This information is for educational purposes only and is not intended as medical advice.

Ready for more Immunology? As immune science educator, I offer a lecture-course Natural Immunity Fundamentals, write a science digest, hold monthly zoom talks and lead weekly science-intensive study groups at Building Bridges in Children’s Health (BBCH Community). Visit BBCH website to become a member.