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Created in 2008, Phoenix Rising is the largest and oldest forum dedicated to furthering the understanding of, and finding treatments for, complex chronic illnesses such as chronic fatigue syndrome (ME/CFS), fibromyalgia, long COVID, postural orthostatic tachycardia syndrome (POTS), mast cell activation syndrome (MCAS), and allied diseases.
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While Long Covid brings about a lot of bad news, the good news is that there is not a single type of organic damage found across all Long Covid sufferers which could explain even a fraction of the complex and evolving symptoms. This indicates Long Covid is due to dysfunction and not damage, making it easily treatable with the right understanding. While there is organic damage found, there is nothing causative and it only seems to be a side product of another process.
The Dysfunction, Not Damage Theory is that the acute phase of COVID19 causes a number of metabolic shifts, pushing the body into metabolic states which are stable but cause dysfunction. Combined with a small amount of (reversible) damage to the mitochondrial membranes, dysfunction of iron homeostasis and an unbalanced microbiome — this seems it can explain all of the complex and evolving symptoms of Long Covid.
Dysfunction, Not Damage Theory:Any one or more of these things happen together, many of them playing off each-other in feedback loops, with the resulting symptoms depending on the deficiencies in the vitamin co-factors and genetic predisposition at the time of oxidative assault, as well as any dormant infections.
- An acute oxidative event causes iron mobilization into the brain and other tissues, causing auto-oxidation, which produces massive oxidative stress and destroys cellular lipids, antioxidants and DNA. The bodies DNA repair system, PARP activates but due to oxidative conditions depletes NAD+and its building blocks, this triggers what I refer to as the “Niacin Sink Trap”.
- At the same time, the production of vitamin B12 is interrupted, because the cobalamine building block is oxidized, triggering the “Methyl Trap”. Both the Niacin Sink Trap and Methyl Trap are stable metabolic dysfunction which cause a variety of evolving and complex symptoms.
- The iron which was mobilized causes oxidative damage to cell membranes and DNA, since the body doesn’t have a mechanism to regulate extra iron well and is bound in the form of ferritin and possibly other compounds. These leak iron due to the bodies pro-inflammatory state and causes evolving and complex symptoms.
- The mitochondrial membranes that got oxidized stick around as they get complexed with proteins, causing fatigue and lower bioenergetic functioning as they can not function properly.
- The microbiome gets remodeled due to iron absorption, triggering microbial community changes, growth of more pathogenic microbes and disruption of gut/brain axis.
- In some people, the oxidative stress/damage will reactivation dormant neurotrophic viruses like EBV and oxidized cell membranes will harbor any dormant Lyme disease pathogens. Parasites may overgrow due to the iron mobilization and oxidative stress as well as the microbiome remodeling.
Analysis based on symptom time progression research:A recent study which surveyed thousands of participants all over the world regarding their disease progression and symptoms, then used statistical analysis and natural language processing found that there are three clusters of symptom progression over time which are highly correlated. This indicates that there are three main mechanisms in long covid and an analysis of the three graphs below indicates the mechanisms are coupled together.
Looking at the clusters below, it appears the three clusters correlate to:
Cluster 1 — Dysbiosis of the Microbiome
Cluster 2 — Niacin Sink Trap and Methyl Trap, Metabolic Dysfunction
Cluster 3 — Iron Mobilization and Dysfunction
This validates the “Dysfunction not Damage” theory of Long Covid and a further analysis of the symptoms and how they correlate to each of these mechanisms paints a very strong picture of the driving mechanisms behind Long Covid.
Thanks for posting! I’m a long hauler myself with fatigue and PEM. Seems like my body is in energy save mode. I would be in Cluster 3 in this hypothesis, but during infection I had gut problems like nausea and bloating which would be Cluster 1.
Ferritin and full iron panel, research shows the ideal ferritin range is below 100. High ferritin puts you at risk but iron can mobilize and deposit even with low ferritin. Again, ferritin and other iron levels do not indicate the amount of iron stored in your nervous system or other tissues but can show if you have large amounts of stored iron that may be “leaking”, and can indicate if its safe to try and chelate iron.
8-OHdG, a DNA damage biomarker, may be most relevant and will be elevated if you have iron releasing from tissues causing oxidation.
High homocystein has been correlated to iron overload disorders although it is also expected to be elevated due to the methyl trap.
Serum copper and Ceruloplasmin enzyme levels can indicate if you have deficiencies in your iron transport system and would be important to understand and may have led to iron redistribution.
Observation of ferritin based Fleischer Rings in the eyes, in some visible under blacklight.
Transcranial sonography can be used to detect changes in some parts of the brain in brain iron accumulation disorders.
T2 hyperintensities of white matter is one of the most common reported MRI findings in those that are suffering from long covid and a paper on iron storage disease states, “T2 hyperintensities in white matter have been reported in most NBIA (Neurodegeneration with Brain Iron Accumulation) subtypes”.