Jeffrey Lubell (EDS, ME/CFS, LongCOVID Research)
@jefflubellc19.bsky.social
I am researching treatments for my daughter, who has hEDS, ME/CFS and other conditions, with implications for #EDS, #MECFS and #LongCOVID. I am a researcher, but not an MD.
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
@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
medrxiv.org
September 22, 2025 at 11:30 AM
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
@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
@lisaquadt.bsky.social), see this thread on the preprint: bsky.app/profile/jeff... 19/20
A new preprint confirms that generalized joint #hypermobility is a risk factor for #LongCOVID, while breaking new ground by examining risks of extreme hypermobility and whether hypermobility risk varies based on severity of initial COVID infection. www.medrxiv.org/content/10.1...
www.medrxiv.org
September 22, 2025 at 11:30 AM
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
@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
September 22, 2025 at 11:30 AM
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
September 22, 2025 at 11:30 AM
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
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...
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...
www.frontiersin.org
September 22, 2025 at 11:30 AM
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....
Impaired Cerebrospinal Fluid 18F-FEPPA Clearance in Long COVID Suggests Altered Glymphatic System Function
242407
Introduction: Long COVID is often associated with neurological symptoms, such as fatigue and cognitive impairment. Recent hypotheses propose a potential link between these symptoms and dysfun...
jnm.snmjournals.org
September 22, 2025 at 11:30 AM
An impaired glymphatic system may compound the problem by inhibiting outflow of CSF. 15/20 jnm.snmjournals.org/content/65/s....
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...
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-...
link.springer.com
September 22, 2025 at 11:30 AM
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...
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...
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...
www.nature.com
September 22, 2025 at 11:30 AM
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...
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...
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...
www.frontiersin.org
September 22, 2025 at 11:30 AM
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
People with a connective tissue disorder may be especially vulnerable to the endothelial damage that characterizes long COVID due to the fragility of their vasculature and slow wound healing
rdcu.be
September 22, 2025 at 11:30 AM
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
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...
Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases - Scientific Reports
Scientific Reports - Ehlers-Danlos syndrome hypermobility type is associated with rheumatic diseases
www.nature.com
September 22, 2025 at 11:30 AM
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...
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
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
academic.oup.com
September 22, 2025 at 11:30 AM
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
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...
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...
link.springer.com
September 22, 2025 at 11:30 AM
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...
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/...
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...
journals.sagepub.com
September 22, 2025 at 11:30 AM
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...
Redirecting
linkinghub.elsevier.com
September 22, 2025 at 11:30 AM
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...
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/...
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...
bmjpublichealth.bmj.com
September 22, 2025 at 11:30 AM
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
September 22, 2025 at 11:30 AM
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
September 22, 2025 at 11:30 AM
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
September 22, 2025 at 11:30 AM
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
There is more data yet to come from the survey. Stay tuned!
September 19, 2025 at 11:52 AM
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.
@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.
September 19, 2025 at 11:52 AM
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.
@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.
September 19, 2025 at 11:52 AM
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...
A new preprint confirms that generalized joint #hypermobility is a risk factor for #LongCOVID, while breaking new ground by examining risks of extreme hypermobility and whether hypermobility risk varies based on severity of initial COVID infection. www.medrxiv.org/content/10.1...
www.medrxiv.org
September 19, 2025 at 11:52 AM
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...