Thread by @AndrewCAhn2

PART I: Connective Tissue & Immune System

#LongCOVID is shedding light on long-ignored, physiological aspects of Post-Viral syndromes (e.g. #MECFS)

One fascinating area is the role of connective tissue (and Ehler Danlos Syndrome #EDS) in their pathophysiologies.

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Anyone following conversations in the #LongCOVID community might be surprised by the oversized prominence that #EDS plays.

Take @meghanor piece in @TheAtlantic where #EDS community is described working w/ #MECFS #ChronicLyme communities on LongCOVID...

theatlantic.com/magazine/archi…

@meghanor @TheAtlantic ... or the discussion that @polybioRF @microbeminded2 has w/ @RuhoyMD about potential link b/w connective tissue laxity & #MECFS.

In this video, the discussion focuses on craniocervical instability as a possible explanation for neurological symptoms.

@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD .. and more recently, a retrospective review from Sweden found that out of 229 patients w/ #MECFS, 41% had hypermobility as defined by Beighton score of 5 and higher.

If an age/gender specific cutoff for hypermobility was used, then prevalence of hypermobility was 50%!

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD Naturally, hypermobility is overrepresented in this cohort of #MECFS - recognizing that only 3% of the general population have hypermobility (vs. 41% in this cohort).

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD .. further, case series on Post-COVID describes: ".. combination of symptoms that occurs so often, that they can be carefully described as a clinical pattern. These manifestations include young age, female gender, joint hypermobility, the onset of pain after COVID-19 .. ."

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD BUT #LongCOVID is recognized as a syndrome of immune dysregulations.

Is there a unifying link b/w connective tissue biomechanics & immune function?

Believe it or not, some evidence exists for this and comes from Acupuncture Research (specifically from @NCCIH_Director)!

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director The story starts in 1990-2000s when Helene Langevin @NCCIH_Director recognized an interesting feature of needling.

When needling, acupuncturist typically look for "de qi" sensation - an aching heaviness that purportedly is a/w greatest therapeutic effect.

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director When this "de qi" is elicited, acupuncturists often feel a "tug" on the needle clasically described "like a fish biting on a fishing line".

This needle grasp can be visualized as a tenting of skin when the needle is pulled.

doi.org/10.1096/fj.01-…

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director Langevin hypothesized that "de qi" grasping occurred through winding of collagen/elastic fiber around the needle.

Through some beautiful images and elegant robotic biomechanical measurements, she proved this hypothesis correct.

Collagen (in blue) shown wrapped around needle.

@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director Furthermore, she showed that acupoints - when mapped against cross sections of cadaveric arm - spatially correlated with fascia between muscles.

~80% of acupoints mapped to inter/intramuscular fascia: e.g., acupoint L3 overlies fascia b/w Biceps & Brachioradialis muscle

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director This was exciting news: here was an anatomical basis for acupuncture & somehow connective tissue might play a role in mediating its therapeutic effects.

@NCCIH_Director initially looked at mechanotransduction - effect of mechanical forces on fibroblast gene expression.

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@meghanor @TheAtlantic @polybioRF @microbeminded2 @RuhoyMD @NCCIH_Director But then focused on effects of biomechanical forces (in connective tissue) on inflammation.

Her intriguing f/u studies showed how mechanical forces can modify inflammation - carrying some implications for #LongCOVID & #EDS: to be covered in Part II of this series.

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