The Hugely Predictive Factor for Long COVID…is also found in ME/CFS and Fibromyalgia: the IACFS/ME Conference II

[SWAlexander]

As I said over a year ago:
Lack of or damaged prostaglandin leads to thrombosis.
Despite test evidence, doctors ignored for 2 years, my low cortisol. Further ignored existing VWF. How many people are tested for VWF, thrombosis and cortisol?

If you can, please read it all.
This is the second in a series of blogs on the IACFS/ME 2022 International Conference on ME/CFS (and long COVID). The last one focused on David Systrom’s Keynote address (https://www.healthrising.org/blog/2022/07/29/systrom-keynote-iacfs-me-conference-long-covid/. This one focused on an hour-long talk that kicked off the keynote session.

excerpt:
Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Connection

Interest in the HPA axis – which regulates the production of cortisol – in ME/CFS dates back 30 years. While the cause of the low morning salivary cortisol was never identified, several problems in the HPA axis did pop up over time.

Several factors made the HPA axis and cortisol an obvious early choice. Cortisol’s regulation of the stress response, metabolism, the sleep-wake cycle, and in suppressing inflammation means it has the potential to affect many of the processes at play in ME/CFS and long COVID. While HPA axis work declined over time, in ME/CFS it never really stopped. One intriguing 2018 ME/CFS study linked epigenetic modifications in T-cells to an impaired response to glucocorticoid hormones, such as cortisol, in a subset of patients. Dr. Klimas’s model-generated protocol for Gull War Illness (GWI) and ME/CFS includes both an immune modulator (etanercept) and drug (mifepristone) that she hopes will reset the HPA axis.

https://www.healthrising.org/blog/2...ng-covid-factor-chronic-fatigue-fibromyalgia/

 

[SWAlexander]

Related to HPA axis

Modeling Neuroimmune Interactions in Human Subjects and Animal Models to Predict Subtype-Specific Multidrug Treatments for Gulf War Illness

Abstract

Gulf War Illness (GWI) is a persistent chronic neuroinflammatory illness exacerbated by external stressors and characterized by fatigue, musculoskeletal pain, cognitive, and neurological problems linked to underlying immunological dysfunction for which there is no known treatment. As the immune system and the brain communicate through several signaling pathways, including the hypothalamic-pituitary-adrenal (HPA) axis, it underlies many of the behavioral and physiological responses to stressors via blood-borne mediators, such as cytokines, chemokines, and hormones. Signaling by these molecules is mediated by the semipermeable blood-brain barrier (BBB) made up of a monocellular layer forming an integral part of the neuroimmune axis. BBB permeability can be altered and even diminished by both external factors (e.g., chemical agents) and internal conditions (e.g., acute or chronic stress, or cross-signaling from the hypothalamic-pituitary-gonadal (HPG) axis). Such a complex network of regulatory interactions that possess feed-forward and feedback connections can have multiple response dynamics that may include several stable homeostatic states beyond normal health. Here we compare immune and hormone measures in the blood of human clinical samples and mouse models of Gulf War Illness (GWI) subtyped by exposure to traumatic stress for subtyping this complex illness. We do this via constructing a detailed logic model of HPA-HPG-Immune regulatory behavior that also considers signaling pathways across the BBB to neuronal-glial interactions within the brain. We apply conditional interactions to model the effects of changes in BBB permeability. Several stable states are identified in the system beyond typical health. Following alignment of the human and mouse blood profiles in the context of the model, mouse brain sample measures were used to infer the neuroinflammatory state in human GWI and perform treatment simulations using a genetic algorithm to optimize the Monte Carlo simulations of the putative treatment strategies aimed at returning the ill system back to health. We identify several ideal multi-intervention strategies and potential drug candidates that may be used to treat chronic neuroinflammation in GWI.
https://pubmed.ncbi.nlm.nih.gov/34445252/

 

[SWAlexander]

 

[Consul]

I think her theory is very nice but i wonder if an issue here is that Giardia appears to be quite potent at inducing ME in ppl, thats an extracellular parasite. In my mind those shouldnt be particularly good at exhausting CD8+ T cells.

 

[Husband of]

As I said over a year ago:
Lack of or damaged prostaglandin leads to thrombosis.
Despite test evidence, doctors ignored for 2 years, my low cortisol. Further ignored existing VWF. How many people are tested for VWF, thrombosis and cortisol?

If you can, please read it all.
This is the second in a series of blogs on the IACFS/ME 2022 International Conference on ME/CFS (and long COVID). The last one focused on David Systrom’s Keynote address (https://www.healthrising.org/blog/2022/07/29/systrom-keynote-iacfs-me-conference-long-covid/. This one focused on an hour-long talk that kicked off the keynote session.

excerpt:
Chronic Fatigue Syndrome (ME/CFS) and Fibromyalgia Connection

Interest in the HPA axis – which regulates the production of cortisol – in ME/CFS dates back 30 years. While the cause of the low morning salivary cortisol was never identified, several problems in the HPA axis did pop up over time.

Several factors made the HPA axis and cortisol an obvious early choice. Cortisol’s regulation of the stress response, metabolism, the sleep-wake cycle, and in suppressing inflammation means it has the potential to affect many of the processes at play in ME/CFS and long COVID. While HPA axis work declined over time, in ME/CFS it never really stopped. One intriguing 2018 ME/CFS study linked epigenetic modifications in T-cells to an impaired response to glucocorticoid hormones, such as cortisol, in a subset of patients. Dr. Klimas’s model-generated protocol for Gull War Illness (GWI) and ME/CFS includes both an immune modulator (etanercept) and drug (mifepristone) that she hopes will reset the HPA axis.

https://www.healthrising.org/blog/2...ng-covid-factor-chronic-fatigue-fibromyalgia/

any indication/consideration/speculation of whether the low cortisol was there before the illness as well?

 

[Violeta]

I have a lot of learning to do about this whole subject, but I feel like we have been ripped off not being told about anandamide's part in this area.

I just found out about anandamide last week, it's new to me, I may be off track. I will bring some info to the table, but there's so much I don't even know where to start at the moment.

 

[SWAlexander]

any indication/consideration/speculation of whether the low cortisol was there before the illness as well?

My low cortisol was diagnosed in 1979. I had at least 3 Addison crises since. My body would not like to recover for weeks.
I wonder how many people never had a cortisol/ADHD test.

 

[Husband of]

Sorry what's the link to adhd? I don't think my wife had adhd but maybe that's just in comparison to me who I think has it quite severely. We joke now that she has just become more like me with MECFS (of course adhd characteristics are not the only nor most concerning impact). I don't know if you k ow the show taskmaster, but I always used to ask her what the task was, pretty much every time after the explained the task. Now she is missing it too. Im having to pay more effort to hear it so I can tell her. (People don't think much about the impacts this disease has on those close to the sufferer lol)

 

[Violeta]

Sorry what's the link to adhd? I don't think my wife had adhd but maybe that's just in comparison to me who I think has it quite severely. We joke now that she has just become more like me with MECFS (of course adhd characteristics are not the only nor most concerning impact). I don't know if you k ow the show taskmaster, but I always used to ask her what the task was, pretty much every time after the explained the task. Now she is missing it too. Im having to pay more effort to hear it so I can tell her. (People don't think much about the impacts this disease has on those close to the sufferer lol)

These are just some thoughts for brainstorming. I am sorry that I can't put it together into a cohesive paragraph at this moment, maybe after I eat breakfast. I may have already burned off all my mental energy this morning.

Orthostatic intolerance (Neurogenic orthostatic hypotension (nOH) is caused by deficient neurotransmission of norepinephrine)

Studies suggest that ADHD could be linked to the dysfunction of dopamine, which is a neurotransmitter that helps control movements and emotions

but some COVID-19 "long-haulers" may actually be dealing with a known condition, called postural orthostatic tachycardia syndrome.

 

[SWAlexander]

"long-haulers" may actually be dealing with a known condition, called postural orthostatic tachycardia syndrome.

Yes, you have a good point. I have been searching for months and their older papers hinting without naming details about POTS in relation to hormones.

This is the latest publication I found that explains also the symptoms:
Excerpt:
How does postural orthostatic tachycardia syndrome (POTS) affect my body?
Normally, when you stand up, gravity causes about 10% to 15% of your blood to settle in your abdomen, legs and arms. This means that less blood reaches your brain, which can cause brief lightheadedness. If you don’t have POTS, this lightheaded feeling doesn’t happen often because your leg muscles help pump blood back up to your heart.
In addition, your autonomic nervous system turns on a series of rapid responses. To compensate for the lower amount of blood returning to your heart after standing up, your body releases the hormones epinephrine (adrenaline) and norepinephrine.
These hormones typically cause your heart to beat a little faster and with more force. Norepinephrine also causes your blood vessels to tighten or constrict. This all results in more blood returning to your heart and brain.
more to read: https://my.clevelandclinic.org/health/diseases/16560-postural-orthostatic-tachycardia-syndrome-pots

 

[Violeta]

One intriguing 2018 ME/CFS study linked epigenetic modifications in T-cells to an impaired response to glucocorticoid hormones, such as cortisol, in a subset of patients.

I wonder if this is related to @Manuel Ruiz' information about B cells and EVB.

From a post by Manuel:
"In this review I describe how the possession of certain ancestral HLA-II alleles (a system used by our immune system to recognize which proteins are foreign, such as pathogens, and which are not) makes the individual genetically weak to control EBV latent cells, thus developing different diseases. EBV infects B cells through a protein on its surface called gp42, which allows it to bind to HLA-II molecules on the B cell surface. If the individual possesses ancestral HLA-II alleles susceptible to EBV, it will cause that after the infection of B cells and the establishment of the latent form, the antigen presentation of these cells will be altered, since gp42 would remain bound to HLA-II molecules interfering in the presentation of antigens to T lymphocytes (necessary to eliminate infected cells), and in the activation of these."

 

[SWAlexander]

Violeta maybe it is not always a virus.
If you like read my posting #17: https://forums.phoenixrising.me/thr...ovid-vaccine-new-research.86191/#post-2377727
"Addison’s disease in antiphospholipid syndrome: a rare complication"

 

[Violeta]

Violeta maybe it is not always a virus.
If you like read my posting #17: https://forums.phoenixrising.me/thr...ovid-vaccine-new-research.86191/#post-2377727
"Addison’s disease in antiphospholipid syndrome: a rare complication"

Do you know what genes they are referring to?

I wonder if the answer to that is in this study.

Glucocorticoids in T cell apoptosis and function

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2792342/

( Although GC-induced cell death does not directly proceed via one of the two classical apoptotic pathways, Bcl-2 proteins and caspases still appear to be involved in this process )

I will look at that thread, thank you.

 

[Violeta]

Manuel: "One of the main reasons why EBV is implicated in the disease is because it binds its glycoprotein 42 to the MHC class II of B lymphocytes and subsequently remains bound after its fusion with the plasma membrane. In addition, it is related to the DRB1 and DQB1 alleles because gp42 binds to the β1..."

Internet: "The most well-known risk factor for autoimmune Addison disease is a variant of the HLA-DRB1 gene called HLA-DRB1*04:04. This and other disease-associated HLA gene variants likely contribute to an inappropriate immune response that leads to autoimmune Addison disease, although the mechanism is unknown."

 

[SWAlexander]

Do you know what genes they are referring to?

As they say in 11 Jul 2022:
The genetic cause of antiphospholipid syndrome is unknown. This condition results from the presence of three abnormal immune proteins (antibodies ) in the blood. The antibodies that cause antiphospholipid syndrome are called lupus anticoagulant, anticardiolipin, and anti-B2 glycoprotein I.

But here is one paper. "Genetic Factors in Antiphospholipid Syndrome: Preliminary Experience with Whole Exome Sequencing" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765384/

And thanks:

HLA-DRB1

Yes, I have 4 genetic markers HLA-DRB1.

 

[Violeta]

You have probably seen this but I'll put it here so I can find it.

The EBV has been associated with thrombosis not via direct increase in the serum coagulability but by the induction of APL antibodies. The APL antibodies are a group of heterogeneous antibodies associated with both arterial and venous thromboses.

 

[SWAlexander]

APL antibodies

Since quite a while I try to encourage people to have a Citrate Test (Instrumentation Laboratory TOP 500 (Coagulation): Citrate) for APS and VWF test, but it is not easy. Most doctors don´t know anything about it and don't like to write a referral to a hematologist. It´s even worse in Germany.