Thread by @JeffLubell_C19

This thread outlines my hypotheses on how leakages from microangiographic blood vessels contribute to pain, inflammation and post-exertional malaise in people w/ #MECFS and #LongCOVID. This mechanism is most pronounced in people with a connective tissue disorder. 1/

The core of my hypotheses is that COVID-19 or other viruses cause damage to endothelial cells in blood vessels, which increase their permeability, leading to the release of interstitial fluid which floods affected tissue, creating hypoxic conditions that trigger inflammation. 2/

The increased interstitial fluid eventually forms subcutaneous adipose tissue, which becomes fibrotic and painful to touch, leading to additional inflammation that releases mast cell mediators that cause further endothelial damage, in a worsening spiral. 3/

The lymphatic vessels that are supposed to take up the fluid also rely on endothelial cells, and if they are damaged, the lymphatic system might become less effective in removing the fluid, contributing to an unhealthy buildup of interstitial / lymphatic fluid. 4/

In addition to the pain from fibrotic adipose tissue, I hypothesize that there can be pain from the build-up of lymphatic fluid which puts pressure on nerves. It’s possible this contributes to the neurological manifestations of thoracic outlet syndrome and MALS 5/

This process is very similar to what is hypothesized to take place in #lipedema, and I expect that many people with #MECFS or #LongCOVID have lipedema or its cousin, Dercum’s disease, in which the fibrotic adipose tissue takes the form of lumps called lipomas. 6/

Hypermobility is very common among people with lipedema, suggesting that people with connective tissue disorders are particularly vulnerable to this set of issues. Not coincidentally, hypermobility is also very common among people with #MECFS. 7/

It is not clear why people with connective tissue disorders are particularly susceptible to this mechanism. One possibility is that they are more likely to have mast cell disorders, contributing to the release of inflammatory mediators that damage endothelial cells. 8/

Another possibility: when joints go out of place, the body responds by flooding the area with fluid to try to heal It – think of the swelling of a sprained ankle. People with hypermobility have more joints go out of place, leading to the release and accumulation of more fluid. 9/

I believe this also contributes to post-exertional malaise. After a major crash, my daughter described a feeling of awfulness throughout her body. Others describe feeling poisoned. We have learned through trial and error that this is related to fluid build-up. 10/

I hypothesize that exercise increases the release of interstitial fluid from damaged blood vessels. I’m not 100% sure why. Three possibilities: increased blood pressure from exercise; increased fluid from joints going out of place; mast cell reactions to new environment 11/

I am also not entirely sure why there is a delay between exercise and the poisoned feeling. One possibility is that tissue can tolerate brief periods of flooding with fluid, but after too long, oxygen is depleted, mitochondria can’t function, etc. 12/

Another possibility: the delay could be related to a biphasic mast cell reaction in which inflammatory mediators that interfere with endothelial function are only released after a period of several hours. My daughter had a biphasic MC reaction the day of her crash. 13/

We have found that manually draining the excess fluid, combined with the squeezing of affected tissue, helps enormously to temporarily relieve symptoms. The manual break-up of fibrotic tissue, while painful, provides longer-lasting relief from pain and discomfort. 14/

When we break-up the fibrotic areas, my daughter describes feeling like stale fluid has been released, and we often need to drain it into the lymph nodes, and especially away from the spine. 15/

One more issue related to the lymphatic system. In the brain, the lymphatic system is called the glymphatic system and studies have shown that problems with the drainage of the glymphatic system contribute to intracranial hypertension. 16/

I hypothesize that this problem can be mechanical, arising from a blockage at the cribriform plate. My daughter experienced a substantial reduction in intracranial pressure when we massaged the bridge of her nose, which released fluid down her spine and throat. 17/

This blog post by @CortJohnson summarizes the evidence for endothelial damage / interference in #MECFS and #LongCOVID. 18/ healthrising.org/blog/2021/12/1…

My blog post describes the connections between #MECFS, #EDS, #Fibromyalgia, and #Lipedema and provides more details on the hypotheses I describe above, with citations. 19/ healthrising.org/blog/2021/12/0…

If my hypotheses are correct, we should prioritize research on several questions: (a) how do we prevent endothelial damage? (b) how do we accelerate the healing of endothelial damage? And (c) how can we systemically treat fibrotic adipose tissue? 20/

Among other research, I would like to see research on whether BPC-157 and other healing peptides can accelerate the healing of endothelial damage. pubmed.ncbi.nlm.nih.gov/27847966/ 21/

A few caveats: I am not a doctor and have no medical training. These hypotheses are based primarily on extended observations of one individual: my daughter, who has #MECFS, #EDS, #POTS, #MCAS, Craniocervical Instability, Chiari, and Tethered Cord Syndrome. 22/

While I have relied heavily on primary research in fleshing out these hypotheses, the full pathway that I describe has not yet been evaluated through research. Research is needed to test these hypotheses. 23/

Also, I do not claim that these mechanisms are the ONLY pathology underlying #MECFS or #LongCOVID. As @amyproal and others shown, there are multiple mechanism through which COVID and other pathogens may cause lasting problems. 24/ frontiersin.org/articles/10.33…

I believe COVID and other viruses cause problems through multiple pathways. This is why #MECFS and #LongCOVID have been so difficult to understand and treat. What I am trying to do in offering these hypotheses is encourage greater attention on the lymphatic system. 25/

Per your request, @coachvirginiap