Jeffrey Lubell (EDS, ME/CFS, LongCOVID Research)

For a summary, check this out: www.bsms.ac.uk/about/news/2...

More to come out of this data set soon!

BREAKING NEWS: Exciting new preprint from
@norrislabs.bsky.social & team documents the results of their genome-wide association study of hEDS and matched controls. Among other findings, they find a strong genetic overlap with #MECFS and other comorbid conditions. medrxiv.org/content/10.1... 20/20

For more detail on findings from our study (with Regina Torok, Rena Rudy, @bendybrain.bsky.social and
@lisaquadt.bsky.social), see this thread on the preprint: bsky.app/profile/jeff... 19/20

Additional research is needed to assess these and other potential explanations and shed light on the pathophysiology of #LongCOVID and related disorders like #MECFS. This in turn should accelerate progress toward treatment. 18/20

Another important question is whether and to what extent other connective tissue disorders increase #LongCOVID risks. There are a lot of connective tissue disorders. While each one may be rare, together they may help explain a lot of the pathogenesis of LongCOVID. 17/20

Frontiers | Long COVID and hypermobility spectrum disorders have shared pathophysiology Hypermobility Spectrum Disorders (HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS) are the most common joint hypermobility conditions encountered by physic...

As part of process of assessing these hypotheses & outlining and testing plausible mechanisms, it will be important to consider how much of risk derives from genetic factors vs. acquired factors. For example, we know viruses can damage connective tissue. 16/20 www.frontiersin.org/journals/neu...

An impaired glymphatic system may compound the problem by inhibiting outflow of CSF. 15/20 jnm.snmjournals.org/content/65/s....

Craniocervical instability in patients with Ehlers-Danlos syndromes: outcomes analysis following occipito-cervical fusion - Neurosurgical Review Craniocervical instability (CCI) is increasingly recognized in hereditary disorders of connective tissue and in some patients following suboccipital decompression for Chiari malformation (CMI) or low-...

Spinal problems such as Chiari malformation and craniocervical instability can impair the drainage of cerebrospinal fluid, resulting in an increase in intracranial pressure that leads to brainstem compression. 14/20 link.springer.com/article/10.1...

Blood–brain barrier disruption and sustained systemic inflammation in individuals with long COVID-associated cognitive impairment - Nature Neuroscience Long COVID is a major public health issue since 2020 and exhibits frequent neurological symptoms. Greene et al. propose that brain fog results from leaky brain blood vessels and a hyperactive immune s...

As vascular and blood-brain barrier permeability increases among people with long COVID due to inflammation & vascular damage, the resulting leakage of protein-rich fluid in brain can increase the volume of glymphatic and cerebrospinal fluid in need of drainage. 13/20 www.nature.com/articles/s41...

Frontiers | Signs of Intracranial Hypertension, Hypermobility, and Craniocervical Obstructions in Patients With Myalgic Encephalomyelitis/Chronic Fatigue Syndrome The pathophysiology of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is unknown. In this study we test the hypothesis that hypermobility, signs...

Finally, the increased #LongCOVID risk from hypermobility could be related to the tendency of people with EDS to experience spinal problems such as Chiari malformation and craniocervical instability. 12/20 www.frontiersin.org/journals/neu...

Fifth, people with connective tissue disorders may be more likely to experience and be slower to recover from the vascular damage that characterizes long COVID and associated damage to the extracellular matrix. 11/20 rdcu.be/dx0o8

Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases - Scientific Reports Scientific Reports - Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases

Fourth, people with #hEDS are particularly susceptible to autoimmune disorders, which play an important role in long COVID. 10/20 www.nature.com/articles/sre...

Proteomic discoveries in hypermobile Ehlers–Danlos syndrome reveal insights into disease pathophysiology Abstract. Hypermobile Ehlers–Danlos Syndrome (hEDS) is a poorly understood connective tissue disorder that lacks molecular diagnostic markers. This study a

A recently released paper from @norrislabs.bsky.social describes some possible pathways through which hEDS may lead to systemic immune dysregulation. academic.oup.com/immunohorizo... . Other mechanisms are described here: www.frontiersin.org/journals/imm... 9/20

Association of mast-cell-related conditions with hypermobile syndromes: a review of the literature - Immunologic Research Ehlers–Danlos syndrome (EDS) is a group of related connective tissue disorders consisting of 13 subtypes, each with its own unique phenotypic and genetic variation. The overlap of symptoms and multitu...

Third. the inter-relationship of connective tissue and mast cells may lead people with #EDS or hypermobility spectrum disorder to be vulnerable to mast cell activation disorders, which can in turn prompt both #POTS and conditions like #LongCOVID and #MECFS. 8/20 link.springer.com/article/10.1...

Improvement in chronic pelvic pain, orthostatic intolerance and interstitial cystitis symptoms after treatment of pelvic vein insufficiency - Steven J Smith, Michael J Sichlau, B Holly Smith, Dacre RT... Objectives Comorbidities associated with venous origin chronic pelvic pain (VO-CPP) were evaluated pre and post venous treatment to assess change. Materials an...

Second, people with #EDS or #hypermobility spectrum disorder are more susceptible to vascular compression syndromes such as May-Thurner syndrome. Potentially, #LongCOVID could cause or aggravate these syndromes. 7/20 journals.sagepub.com/doi/10.1177/...

First, vascular laxity may make people with #EDS vulnerable to orthostatic intolerance (such as #POTS) due to the distension of veins from hydrostatic pressure, which increases venous pooling. 6/20 www.autonomicneuroscience.com/article/S156... & linkinghub.elsevier.com/retrieve/pii...

Variant connective tissue as a risk factor for long COVID: a case-control study of data from a retrospective online survey of adults in the USA and UK Introduction This study explored the extent to which two measures of joint hypermobility, a marker of variant connective tissue, predict the development of long COVID after COVID-19 infection, and whe...

We do not know with certainty why people with #hypermobility are more likely to experience #LongCOVID symptoms, but we have some hypotheses. Here are seven potential explanations culled from our article that merit further investigation. 5/20 bmjpublichealth.bmj.com/content/3/2/...

Similarly, if you think that #hEDS and hypermobility spectrum disorder are simply benign conditions that cause joints to go out of place, you need to explain why people with these disorders are more likely to experience #LongCOVID and other post-viral conditions. 4/20

Whether your hypothesis is that #LongCOVID is caused by viral persistance, vascular damage, or microclots, a key litmus test for this hypothesis ought to be whether you can explain why this mechanism is more likely to occur in people with #hEDS. 3/20

Before reviewing possible mechanisms discussed in the paper, I want to pause and discuss why this information will be helpful. In brief, this information will help shed light on the pathophysiology of both #LongCOVID and hypermobility disorders like #hEDS. 2/20

Our paper found that people with generalized joint #hypermobility have a 23% higher risk of #LongCOVID while people with extreme hypermobility have a 76% higher risk of #LongCOVID. This thread focuses on possible explanations for the higher risk. 1/20

There is more data yet to come from the survey. Stay tuned!

Authors include: Regina Torok, Rena Rudy,
@bendybrain.bsky.social, @lisaquadt.bsky.social, and me. Much thanks to @ehlersdanlos.bsky.social and Ehlers-Danlos Syndrome Research Foundation for providing funding for the research and to everyone who participated in the survey.

We hope the article will prompt further research on WHY people with hypermobility conditions like #hEDS are more vulnerable to #LongCOVID. I'll post a thread in the next few days with some hypotheses about this.

In a nutshell, we found that people with generalized joint hypermobility are at increased risk of #LongCOVID and people with extreme hypermobility are at particular risk. This thread has more detail on the findings: bsky.app/profile/jeff...

Variant connective tissue as a risk factor for long COVID: a case-control study of data from a retrospective online survey of adults in the USA and UK Introduction This study explored the extent to which two measures of joint hypermobility, a marker of variant connective tissue, predict the development of long COVID after COVID-19 infection, and whe...

Our article examining the extent to which people with #hypermobility are at risk of Long COVID was just published in BMJ Public Health, an open access journal. bmjpublichealth.bmj.com/content/3/2/...

Authors include: Regina Torok, Rena Rudy, @bendybrain.bsky.social, @lisaquadt.bsky.social and me. Appreciate the ongoing collaboration!

For more background, see this thread: threadreaderapp.com/thread/18962... . I will post a subsequent thread reviewing potential hypotheses for why hypermobility leads to increased #LongCOVID risk.

(d) Both GJH and extreme hypermobility are predictors of having severe symptoms during initial COVID infection in a regression controlling for age, gender at birth, number of COVID infections and number of vaccine doses.

(c) risk varies by severity of initial infection. Both GJH and extreme hypermobility are strong predictors of Long COVID among those with mild or no symptoms from initial infection, but not significant predictors of Long COVID among those with severel initial symptoms; and