Over the next 3 days we'll be tweeting the IACFS/ME conference! The amazing lineup is available here: iacfsme.org/2021-iacfsme-v…
Tweets by @AlisonSbrana, @ItsAngInLA, & @ahandvanish.
Follow this thread! #LongCovid
1/
Tweets by @AlisonSbrana, @ItsAngInLA, & @ahandvanish.
Follow this thread! #LongCovid
1/
Dr. Jarred Younger is up to talk about imaging techniques for neuroinflammation. He has found a way to visualize elevated temperature in the brain and found that people with ME have pockets of heat across the brain - up to 100.8F!
This is related to overactivated microglia.
2/
This is related to overactivated microglia.
2/
He talks about how we're repeating research in #LongCOVID and how we need to be focused on treatments & clinical trials right now, prioritizing the drugs we think will work, which he says there are a ton of. We can't wait for a perfect biomarker before we start trials.
3/
3/
He puts up a list of ~50 potential substances and drugs he's hopeful about & would like to see trialed.
*A note that we can't take screenshots for this conference so will try to communicate as much as possible without.
4/
*A note that we can't take screenshots for this conference so will try to communicate as much as possible without.
4/
Next up is Dr. Peter Rowe (who is a pediatric ME expert) talking about Orthostatic Intolerance & the overlap between Ehlers-Danlos as well.
5/
5/
The symptoms of Orthostatic Intolerance (OI): high heart rate, fatigue, brain fog. Fatigue and brain fog don't resolve while lying down, where others do.
6/
6/
He shows a diagram of the mechanism, where arterial pressure ends up creating a dysfunction of the sympathetic nervous system.
7/
7/
He mentions there is a lot of acrocyanosis in people with this condition (relevant to #LongCOVID)!
8/
8/
There is increased blood pooling in these patients, likely related to inability to vasoconstrict. Blood volume is reduced by about 10%, leading to a decrease in blood brain flow.
9/
9/
After 30 minutes upright, healthy controls had a 7% reduction in the blood brain flow, compared to 30% in people with POTS. #LongCovid
The number of symptoms *also* correlated with the amount of blood brain flow.
10/
The number of symptoms *also* correlated with the amount of blood brain flow.
10/
He is now showing data that objectively proves that deconditioning is not the mechanism behind this.
12/
12/
Hypermobility is a risk factor for this! ME patients with hypermobility had worse results than ME patients without hypermobility.
13/
13/
He's now showing data from a #LongCOVID patient whose data looks similar to the earlier POTS data, where the patient had a heartrate increase of 77 BPM after standing.
14/
14/
Next up is @MBVanElzakker!
He'll be talking about the dorsal brainstem - the part of your brain that merges the brain with your spine.
15/
He'll be talking about the dorsal brainstem - the part of your brain that merges the brain with your spine.
15/
@MBVanElzakker There are lots of structures and circuits near each other and they tend to activate each other, in part due to glia priming (like Dr. Younger talked about earlier).
16/
16/
@MBVanElzakker This includes the vagus nerve - named after 'vagabond' since it connects so many parts of the body (sensory and motor behaviors).
17/
17/
@MBVanElzakker The vagus nerve also detects adrenaline, detects inflammation, and surveys the gut microbiome, among so many other functions.
Importantly, it also initiates the "central illness response" (why you feel the way you do when you're sick) & triggers the neuroimmune response.
18/
Importantly, it also initiates the "central illness response" (why you feel the way you do when you're sick) & triggers the neuroimmune response.
18/
@MBVanElzakker There are many structures in this area that influence inflammation/pain signaling, autonomic control of blood pressure and breathing, changes in heart rate, all which aren't working very well in these patients.
19/
19/
@MBVanElzakker In a mouse model, mice were given a bacteria responsible for food poisoning, and these structures were activated in these mice.
This is much harder to study in humans!
20/
This is much harder to study in humans!
20/
Next up is Dr. Afrin who is an expert in MCAS (mast cell activation syndrome) which many #LongCOVID patients have been experiencing.
21/
21/
Mast cells are related to heparin, histamine, and tryptase.
22/
22/
Mast cell diseases ultimately inappropriate activation of mast cells, in some cases including inappropriate/dangerous proliferation.
MCAS is inappropriate activation of mast cells without inappropriate proliferation of mast cells. #LongCOVID #pwME
23/
MCAS is inappropriate activation of mast cells without inappropriate proliferation of mast cells. #LongCOVID #pwME
23/
MCAS is a chronic multisystem polymorbidity that includes:
-inflammation
-allergic-type phenomenon
-aberrencies in growth/development, usually more benign than malignant
-some rare patients have nonstop anaphylaxis
24/
-inflammation
-allergic-type phenomenon
-aberrencies in growth/development, usually more benign than malignant
-some rare patients have nonstop anaphylaxis
24/
It's a waxing/waning illness with flares and periods of remission.
We now know tryptase is usually normal but heparin and others are not.
25/
We now know tryptase is usually normal but heparin and others are not.
25/
Now, Dr. Kauffman is speaking. He noted they often see the “septad” in patients with #MECFS (and #LongCovid too.)
Septad includes:
- MCAS
- hEDS/HSD
- SIBO and/or gastroparesis
- dysautonomia (often POTS)
- infection
- autoimmunity
- cervical instability
26/
Septad includes:
- MCAS
- hEDS/HSD
- SIBO and/or gastroparesis
- dysautonomia (often POTS)
- infection
- autoimmunity
- cervical instability
26/
Now Irina Rozenfeld, DNP, MSHS, APRN from @NSU_INIM with her talk Philosophy of Integrative Medicine: Healing-Oriented Medicine.
Integrative medicine is "root cause medicine." Looking at the whole body, instead of one body system at a time.
27/
Integrative medicine is "root cause medicine." Looking at the whole body, instead of one body system at a time.
27/
She talks about how to maximize the optimal healing environment when practicing integrative medicine. The most important part is for the provider to listen and have *empathy* (not sympathy) for the patient.
28/
28/
Rozenfeld addressed supplement use –– the importance of working w/ a provider when taking supplements & buying quality supplements. She mentions it's not necessarily safe to buy supplements on Amazon. She encourages to check w/ your provider for recommendations where to buy.
29/
29/
Cont'd - Compounding pharmacies are also an option.
Rozenfeld also notes that MedScape and NIH both have online sources for checking drug-supplement interactions. Here is one of the NIH resources she mentions: ods.od.nih.gov/factsheets/lis…
30/
Rozenfeld also notes that MedScape and NIH both have online sources for checking drug-supplement interactions. Here is one of the NIH resources she mentions: ods.od.nih.gov/factsheets/lis…
30/
Q&A: Question about CCI in ME/CFS, especially in infection-triggered cases. Dr. Kaufman notes we're just on the frontier, on the leading edge, of trying to understand this. He notes this is a complex question that's difficult to answer in a short period of time.
31/
31/
Q&A about pacing: Eleanor Stein answers that pacing is about structuring your day as much as possible to avoid PEM (post-exertion malaise.) It's not about exercise––it's about how to conserve energy in your daily life.
32/
32/
Q&A for Dr. Kaufman: Can a patient do a NASA lean test on their own while on beta blockers?
Dr. Kaufman notes his answer may be controversial, but he does not ask patients to stop any meds, salt or fluid loading while testing. More explanation on next tweet:
33/
Dr. Kaufman notes his answer may be controversial, but he does not ask patients to stop any meds, salt or fluid loading while testing. More explanation on next tweet:
33/
Q&A on NASA lean test cont'd: He wants to measure how the patient is in daily life, while on medications or salt/fluid loading. He uses the NASA lean test constantly to determine how to adjust meds etc, not only for initial diagnosis.
This may be helpful for #LongCovid pts.
34/
This may be helpful for #LongCovid pts.
34/
Really excited for next talk by @MBVanElzakker & @microbeminded2 in #IACFSME conference:
The Functional Anatomy and Mechanisms of Feeling Sick: A Workshop on the Intersection of Neuroimmunology, the Autonomic Nervous System, & How They Can Be Impacted by Environmental Factors
35/
The Functional Anatomy and Mechanisms of Feeling Sick: A Workshop on the Intersection of Neuroimmunology, the Autonomic Nervous System, & How They Can Be Impacted by Environmental Factors
35/
Thanks for the shout-out to the @patientled research study @MBVanElzakker –– he noted the commonality between #LongCovid symptoms and #MECFS while discussing the diagnostic criteria of #MECFS
36/
36/
This is an exceptional, fast-moving talk w/ important graphics. We cannot share any graphics due to conference rules. Dr. VanElzakker's lecture is excellent & graphics are needed to explain physiology. I'll do my best to summarize as able –– *highly* recommend this recording.
37/
37/
@microbeminded2 on now discussing chronic viral infections and it's relation to #MECFS and #LongCovid. She recommends learning from Dr. John Chia who has been studying enterovirus for years. Here's some info on him: healthrising.org/chronic-fatigu…
38/
38/
@microbeminded2 talking about persistent infection in #LongCovid. Talks about autopsy study out of Germany looking for SARS-COV-2 –– they found infection in cranial nerves. "Does the virus fully clear from these areas in pts. with chronic symptoms?" Ongoing research matters
39/
39/
"We need to move beyond looking at body fluids for chronic infection. They hide in tissue & infect nerves. Herpes virus are neurotropic pathogens––they move through nerves in their life cycles. We need to look for pathogens in #MECFS in areas where they expect to be" - Amy Proal
Not all #MECFS are infection-triggered, however @microbeminded2 noting here that we need to look further in those patients for persistent viruses.
"What are the viruses doing in patients with #MECFS that they are not doing in healthy patients?"
41/
"What are the viruses doing in patients with #MECFS that they are not doing in healthy patients?"
41/
"Humans are not sterile by a long shot." There are lots of bacteria in the gut, and there are viruses that infect those bacteria. The research started in the gut, in the mouth, in the skin but now the more we turn the research to other organs, the more we will learn.
42/
42/
The immune system keeps this all in check. But under periods of stress, it's possible the organisms collectively move towards dysbiosis (as opposed to gut homeostasis.) Gut epithelial barrier can become permeable as can oral mucosa, & can move into connective tissue.
43/
43/
"Oral pathogens leaking into blood and into tissue could be part of the story of why we see connective tissue disorders. In other words, there may be an infectious component to connective tissue disorder. It may not be the whole story but it could be part."
- @microbeminded2
44/
- @microbeminded2
44/
Now Amy is talking briefly about craniocervical instability & brainstem compression in #MECFS . The CCI and compression can lead to glial activation, mast cell activation.
45/
45/
Amy is discussing the multiple hits theory –– multiple infections can collectively slow immune response and activate/prime microglia. "Like a snowball rolling down a hill."
- Amy Proal (@microbeminded2 with @polybioRF )
46/
- Amy Proal (@microbeminded2 with @polybioRF )
46/
About to conclude the talk. Lastly, Amy Proal giving examples of 3 theoretical patients who could be diagnosed with #MECFS:
Example 1: First patient has mycotoxin in lungs. And as Dr. Kaufman mentioned, patient also has SIBO in gut. Enterovirus involvement as well.
47/
Example 1: First patient has mycotoxin in lungs. And as Dr. Kaufman mentioned, patient also has SIBO in gut. Enterovirus involvement as well.
47/
Amy giving second example: a patient with craniocervical instability, and also an HHV-6 direct infection of vagus nerve which is continually priming vagus nerve.
#MESpine
48/
#MESpine
48/
Amy giving third example: They previously were infected with Epstein-Barr virus, have gut microbiome dysbiosis, and now were infected with SARS-CoV-2. (This is relevant to #LongCovid )
All 3 patients can be dx with #MECFS––we need to look deeper at root causes.
49/
All 3 patients can be dx with #MECFS––we need to look deeper at root causes.
49/
Final takeaways of this excellent talk by @polybioRF researchers @MBVanElzakker & @microbeminded2 at #IACFSME conference:
1 (of 6): "Dorsal brainstem contains nuclei that control sickness behavior response (pain, nausea, autonomic signaling.)"
50/ #LongCovid #MECFS
1 (of 6): "Dorsal brainstem contains nuclei that control sickness behavior response (pain, nausea, autonomic signaling.)"
50/ #LongCovid #MECFS
"2. Vagus nerve innervates every major trunk organ of body & enters brain at dorsal brainstem
3. Vagus nerve to dorsal brainstem signaling can become activated by dif environmental factors
4. This can activate/prime microglia in dorsal brainstem region, lead to neuroinflammation"
3. Vagus nerve to dorsal brainstem signaling can become activated by dif environmental factors
4. This can activate/prime microglia in dorsal brainstem region, lead to neuroinflammation"
Cont'd summary points from @microbeminded2 and @MBVanElzakker :
5. "Multiple hits can augment this microglial priming and sustain neuroinflammation
6. No two patients have to have exact same mix of "hits" for this activity to contribute to chronic symptom development."
51/
5. "Multiple hits can augment this microglial priming and sustain neuroinflammation
6. No two patients have to have exact same mix of "hits" for this activity to contribute to chronic symptom development."
51/
That was an *outstanding* lecture by @microbeminded2 and @MBVanElzakker at the #IACFSME conference 👏
When recording is available, highly recommend researchers working on #LongCovid watch. Engaging, packed with information. To learn more about them in meantime: @polybioRF
52/
When recording is available, highly recommend researchers working on #LongCovid watch. Engaging, packed with information. To learn more about them in meantime: @polybioRF
52/
We're about to start Day 2!
The first few talks today are on a big topic - what's the overlap between #LongCOVID & Myalgic Encephalomyelitis?
#pwME
53/
The first few talks today are on a big topic - what's the overlap between #LongCOVID & Myalgic Encephalomyelitis?
#pwME
53/
Dr. Avindra Nath is up!
He mentions that the % of people who think they have loss of sense of smell & taste is much smaller than those who actually do on testing (meaning many people don't notice it).
54/
He mentions that the % of people who think they have loss of sense of smell & taste is much smaller than those who actually do on testing (meaning many people don't notice it).
54/
He's moving on to talk about #LongCOVID. He's warning providers to not jump to this diagnosis without ruling out other issues (presumably clotting, encephalitis).
55/
55/
He says there are 4 main groups of #LongCOVID symptoms:
1) Fatigue, which really means exercise intolerance. He gives an example of a cardiologist who is no longer able to climb stairs/see patients.
2) Brain fog, with cognitive dysfunction & word finding difficulties.
56/
1) Fatigue, which really means exercise intolerance. He gives an example of a cardiologist who is no longer able to climb stairs/see patients.
2) Brain fog, with cognitive dysfunction & word finding difficulties.
56/
3) Autonomic intolerance, with high heart rate, persistent fever, night sweats, gastroparesis, peripheral vasoconstriction, sometime blood pressure.
4) Ache & pains, closer to fibromyalgia, muscle & joint pain.
57/
4) Ache & pains, closer to fibromyalgia, muscle & joint pain.
57/
A study of several million Americans shows that 10-30% of patients will fall in the above groups at 6 months after onset!! #LongCOVID
58/
58/
He's showing PET scans of #LongCOVID patients where the cortical ribbon doesn't light up, showing systemic involvement within the brain.
59/
59/
He's showing a graph comparing COVID effects to another virus showing that COVID manifestations happen both more frequently overall and more frequently over time.
60/
60/
He's showing a German study that shows:
-monocytes in the CFS
-decreased interferon responses
-T cell exhaustion!!
-innate immune activation, which is hard to turn off and "is the most abnormal immune finding in this population"
#LongCOVID
61/
-monocytes in the CFS
-decreased interferon responses
-T cell exhaustion!!
-innate immune activation, which is hard to turn off and "is the most abnormal immune finding in this population"
#LongCOVID
61/
Another German study shows macrophages in perivascular regions within the brain as well as activated glia cells.
#LongCovid
62/
#LongCovid
62/
Some patients have white matter lesions in the brain.
63/
63/
Severe COVID can involve both Large and Small Cerebral Vessel involvement.
64/
64/
He's now talking about the autopsies of 19 patients from NYC who all had sudden death outside of the hospital. (He had mentioned sudden death earlier in relation to Ondine's Curse, and that it's more common in COVID in the acute phase).
65/
65/
He says: the brainstem seems to be more involved than other parts of the brain! This is relevant to @MBVanElzakker's talk from yesterday.
66/
66/
-There is a lot of fibrinogen leakage as well.
-Endothelial cells may be the primary injury, platelets secondary.
-There is loss of neurons and microglial activation, eating up the neurons.
#LongCOVID
67/
-Endothelial cells may be the primary injury, platelets secondary.
-There is loss of neurons and microglial activation, eating up the neurons.
#LongCOVID
67/
What treatments are available for #LongCOVID patients?
If persistent infection: we need antivirals
If immune dysregulation: immune suppression
If immune is exhaustion: we need to reverse the exhaustion
68/
If persistent infection: we need antivirals
If immune dysregulation: immune suppression
If immune is exhaustion: we need to reverse the exhaustion
68/
His summaries:
-there is phenotypic overlap between ME and #LongCovid
-immune dysregulation in innate immune response
-*the major target of the immune dysregulation are the endothelial cells!*
69/
-there is phenotypic overlap between ME and #LongCovid
-immune dysregulation in innate immune response
-*the major target of the immune dysregulation are the endothelial cells!*
69/
-the possibility of viral persistence and viral protein-mediated immune response needs to be explored
-clinical trials for early intervention especially around immune system are needed
70/
-clinical trials for early intervention especially around immune system are needed
70/
First Q for Dr. Nath:
I'm a ME patient with many same symptoms including internal vibrations (not mentioned here). Can you tell us what you know about internal vibrations?
71/
I'm a ME patient with many same symptoms including internal vibrations (not mentioned here). Can you tell us what you know about internal vibrations?
71/
A: He hadn't heard of them, talked to experts, but no one really knows what they are. May be related to dysfunctional sensory system, where patients actually sense their organs (usually these sensations are ignored). [An aside from us-internal tremors can be related to SFN!]
72/
72/
Q: Is the glymphatic system related?
A: Likely, it's involved in every neuroinflammatory disease. We assume this is a given, it has to be involved.
#LongCOVID
73/
A: Likely, it's involved in every neuroinflammatory disease. We assume this is a given, it has to be involved.
#LongCOVID
73/
A few Qs about neuro effects after the vaccine; he mentions this needs to be studied, including immune responses after the vaccine.
74/
74/
Q from a reporter: is the immune dysfunction the same as in ME/CFS?
A: There are overlaps in symptoms and pathophysiology; yes there is immune dysregulation in both of them, both in innate and adaptive immune responses.
75/
A: There are overlaps in symptoms and pathophysiology; yes there is immune dysregulation in both of them, both in innate and adaptive immune responses.
75/
Q: should #LongCOVID providers be actively watching for ME/CFS? If so what clinical signs should be observed.
A: Yes but not until everything else is ruled out (kidney damage, heart damage, clots, encephalitis, etc)
A: Yes but not until everything else is ruled out (kidney damage, heart damage, clots, encephalitis, etc)
Q: What do you make of the study in kids that showed presence of COVID leaking in the gut?
A: there could be persistent reservoirs; it makes sense to me.
77/
A: there could be persistent reservoirs; it makes sense to me.
77/
Q: role of EBV reactivation?
A: EBV reactivations is complex. Every neuroinflammatory illness causes EBV reactivation. It's the effect of dysregulation. We need to know what EBV causes as well. It's hard to study; we need a drug to block EBV or to vaccinate against EBV.
78/
A: EBV reactivations is complex. Every neuroinflammatory illness causes EBV reactivation. It's the effect of dysregulation. We need to know what EBV causes as well. It's hard to study; we need a drug to block EBV or to vaccinate against EBV.
78/
Q: role of autoantibodies to neural targets?
A: not sure, but researchers need to be careful with interpretation of autoantibody literature; you'll find them often in neuroinflammatory conditions. The ones that are important are the ones to cell membrane receptors. #LongCOVID 79/
A: not sure, but researchers need to be careful with interpretation of autoantibody literature; you'll find them often in neuroinflammatory conditions. The ones that are important are the ones to cell membrane receptors. #LongCOVID 79/
Going back a bit to explain his past research. They've looked for enterovirus proteins in the blood. In one study they found one in 97% of ME patients. 81/
Of their ME patients who got COVID:
14/26 felt worse after COVID. 1 of them had been in remission (after treatment with Chinese herbs) but got cognitive dysfunction/memory loss after COVID to the point where she had to retire.
1 got worse after vaccination.
#pwME
82/
14/26 felt worse after COVID. 1 of them had been in remission (after treatment with Chinese herbs) but got cognitive dysfunction/memory loss after COVID to the point where she had to retire.
1 got worse after vaccination.
#pwME
82/
Looking at the Depaul Symptom Questionnaire (DSQ) [side note, Dr. Jason has created many useful validated tools!] along with some new CDC symptoms.
84/
84/
502 ME patients were compared to 278 initial COVID and COVID patients at about 5.5 months. (Higher scores = more difficulties).
85/
85/
Findings/differences in sleep symptoms:
-COVID patients had worse "needing to sleep all day" and "needing to nap" at their acute stage, but ME patients had worse symptoms overall.
-Some COVID patients got better
-COVID patients had worse "needing to sleep all day" and "needing to nap" at their acute stage, but ME patients had worse symptoms overall.
-Some COVID patients got better
Findings/differences in cognitive symptoms:
-ME patients were worse over all symptoms
-Some COVID patients cog symptoms got worse between acute and 5.5 months, especially trouble finding words, difficulty focusing, sensitivity to smells, and absent mindedness
#LongCovid
87/
-ME patients were worse over all symptoms
-Some COVID patients cog symptoms got worse between acute and 5.5 months, especially trouble finding words, difficulty focusing, sensitivity to smells, and absent mindedness
#LongCovid
87/
Other findings:
-ME patients had worse endocrine symptoms than both COVID acute and COVID at 5.5 months
-COVID patients had worse headaches than ME patients
-COVID patients had worse orthostatic intolerance at the acute phase, and a few worse OI symptoms at 5.5 months
88/
-ME patients had worse endocrine symptoms than both COVID acute and COVID at 5.5 months
-COVID patients had worse headaches than ME patients
-COVID patients had worse orthostatic intolerance at the acute phase, and a few worse OI symptoms at 5.5 months
88/
Overall:
-ME patients had worse gastrointestinal & neurocognitive symptoms
-ME patients had worse of all symptoms compared to the COVID 5.5 months except orthostatic intolerance
#LongCOVID #pwME
89/
-ME patients had worse gastrointestinal & neurocognitive symptoms
-ME patients had worse of all symptoms compared to the COVID 5.5 months except orthostatic intolerance
#LongCOVID #pwME
89/
Adding to IACFS/ME coverage. One of our team members crashed after covering yesterday’s lectures and couldn’t watch this talk on research from Mt. Sinai on #LongCovid today, but thankfully our friends at @MEActNet covered it:
90/
90/
https://twitter.com/MEActNet/status/1428832945033285637
@MEActNet First up is Dr. Wakiro Sato talking about developing a blood biomarker for ME using Deviated B Cell Receptor Repertoire.
92/
92/
@MEActNet This is based on other research showing deviated B cell subsets, defects in B cell development, autoantibodies, and patients responding to B cell depletion therapies & immunoabsorption therapies.
93/
93/
@MEActNet His past work has identified an alteration of the local right brain network related to B1-AdR-Ab in the right dorsolateral prefrontal cortex, which involves attention and working memory, & B2-AdR-Ab in the right prefrontal cortex, which plays a role in the modulation of pain. 94/
@MEActNet Overall:
-ME characterized by skewed B cell receptor gene usage
-Upregulation of some IGHV genes correlate with infection-related episodes at onset
-Plasmablasts of ME patients upregulated interferon response genes
-B cell receptor repertoire analysis can be diagnostic marker 95/
-ME characterized by skewed B cell receptor gene usage
-Upregulation of some IGHV genes correlate with infection-related episodes at onset
-Plasmablasts of ME patients upregulated interferon response genes
-B cell receptor repertoire analysis can be diagnostic marker 95/
@MEActNet He mentions they're now doing research on #LongCOVID which is coming up with a lot of the same findings.
They also have a Long COVID clinic at NCNP hospital in Tokyo.
96/
They also have a Long COVID clinic at NCNP hospital in Tokyo.
96/
@MEActNet Next up is Dr. Anna Gil. Her talk is:
"Immune Dysregulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID-19 Syndromes:
CD8 T-cell Overactivation and Exhaustion, Increased CD4+CD8+ T-cells and Aberrant Cytokines"
#LongCOVID #pwME
97/
"Immune Dysregulation in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID-19 Syndromes:
CD8 T-cell Overactivation and Exhaustion, Increased CD4+CD8+ T-cells and Aberrant Cytokines"
#LongCOVID #pwME
97/
@MEActNet 5-9 million people in the US are affected with #LongCOVID, 2 million people with ME.
Long COVID is a chance to understand ME pathogenesis!
98/
Long COVID is a chance to understand ME pathogenesis!
98/
@MEActNet Their hypothesis: both conditions are related to a permanently dysregulated immune system, with overactivation of CD8 T cells, leading to T cell exhaustion. #LongCOVID #pwME
99/
99/
@MEActNet They found an increased CD4:CD8 ratio is found in both patients with ME and #LongCOVID patients.
100/
100/
@MEActNet Summary of similarities between #LongCOVID and #pwME:
-increased frequency of CD4+CD8+ T cells and low CD8 cell frequency
-exhausted CD8 T cells
-reactivation of other viruses
101/
-increased frequency of CD4+CD8+ T cells and low CD8 cell frequency
-exhausted CD8 T cells
-reactivation of other viruses
101/
@MEActNet Summary of differences:
-ME has increase CTLA expression on CD8 cells (probably from longer exhaustion)
-Long COVID has higher numbers of dim CD8 cells, suggesting highly activated T cells
-functional exhaustion greater in #pwME (likely bc all patients were sick >5 years)
102/
-ME has increase CTLA expression on CD8 cells (probably from longer exhaustion)
-Long COVID has higher numbers of dim CD8 cells, suggesting highly activated T cells
-functional exhaustion greater in #pwME (likely bc all patients were sick >5 years)
102/
Next up Dr. Leonard Jason with predictable risk factors for developing ME/CFS. This is after EBV but relevant for #LongCOVID.
103/
103/
4500 college students followed for 4 years; 5% were diagnosed with mono. At 6 months, 8% still had symptoms.
104/
104/
Three groups:
1. ME/CFS group
2. Severe ME/CFS
3. Recovered
IL-13 & IL-5 baseline levels were different between the groups.
105/
1. ME/CFS group
2. Severe ME/CFS
3. Recovered
IL-13 & IL-5 baseline levels were different between the groups.
105/
One big difference between groups was pre-existing gastrointestinal issues, including bloating, stomach pain, and irritable bowel symptoms.
#pwME #LongCovid
106/
#pwME #LongCovid
106/
11.9% of the control group had GI symptoms vs 36.8% of the severe ME/CFS group.
107/
107/
They've created a formula for predicting risk of developing ME, which includes the above gastro symptoms, IL-13 and IL-5. #pwME #LongCOVID
108/
108/
Q&A.
Q: does T cell exhaustion act as a protective measure?
A: (Dr. Gil) generally yes, it's how the host can protect itself from the damaging function of an overactive immune system. But T cell exhaustion is bad, esp related to tumor environments, we want to mobile them.
109/
Q: does T cell exhaustion act as a protective measure?
A: (Dr. Gil) generally yes, it's how the host can protect itself from the damaging function of an overactive immune system. But T cell exhaustion is bad, esp related to tumor environments, we want to mobile them.
109/
Q: on cytokines and pre-existing environments in ME/CFS
A: (Dr. Jason) we found pre-existing deficiencies in IL-13 and IL-5 in the severe ME/CFS patients.
110/
A: (Dr. Jason) we found pre-existing deficiencies in IL-13 and IL-5 in the severe ME/CFS patients.
110/
Comments (from Dr. Chia) - Causes of the GI symptoms before EBV infection? Enteroviruses are known association with functional dyspepsia, IBS symptoms, & I've documented 3 cases of delayed seroconversion of EBV/development of CFS following prior CVB4 infection 6-8 months.
111/
111/
Dr. Raijmakers up next talking about neuroinflammation in the brain.
Neuroinflammation is driven by activated microglia. He shows other work that shows neuroinflammation in the amygdala, cingulate, thalamus, hippocampus, midbrain, & pons in ME/CFS patients.
112/
Neuroinflammation is driven by activated microglia. He shows other work that shows neuroinflammation in the amygdala, cingulate, thalamus, hippocampus, midbrain, & pons in ME/CFS patients.
112/
He's showing a graphic that shows the inflammation to neuroinflammation pathway - they think it can happen in either/both the humoral path (through the blood) or neuro path (through the nerves, including the vagus nerve).
113/
113/
However their own study didn't find neuroinflammation. But this might be due to outdated technology, small patient cohort, or maybe the length of time their patients were ill (much longer than the other study) so maybe they represented depleted findings.
114/
114/
Next up is Dr. Gudrun Lange on cognitive assessments in patients with and without ME/CFS! #pwME #LongCOVID
115/
115/
Their objectives: measure cognitive function and exercise capacity in ME/CFS patients, as well as to measure changes in cognitive dysfunction during post-exertional malaise.
Especially in processing speed and working memory.
116/
Especially in processing speed and working memory.
116/
Used TOPF at baseline, WAIS-IV Digit Span pre- and post-exercise, and CogState at 5 points (pre- and post- exercise and then 3 times at specific hourly intervals at home).
117/
117/
Patients with ME had slower reaction times at all timepoints, but especially at the last timepoint after exercise (usually there is a delay in post-exertional effects)
118/
118/
Compared to controls, #pwME had:
-normal levels of information processing *accuracy*
-significantly slower processing speed
-significantly worse performance on decision making when time pressure or a working memory component is involved
119/
-normal levels of information processing *accuracy*
-significantly slower processing speed
-significantly worse performance on decision making when time pressure or a working memory component is involved
119/
The next talk is Dr. Sommerfelt on Severe & Very Severe ME patients in Norway.
120/
120/
About 15% of ME patients have Severe ME (housebound, partially bedridden, can eat and brush teeth) and 1% have Very Severe ME (fully bedridden, some tubefed).
They did a survey for 491 clinically diagnosed patients (or their caregivers) to answer. #pwME
121/
They did a survey for 491 clinically diagnosed patients (or their caregivers) to answer. #pwME
121/
They found an increase in onset of very severe ME cases between 2003 and 2007.
Key findings:
-high levels of very severe ME in kids age 0-19 (very severe ME is associated with childhood onset age 0-15 years)
-45% of very severe patients lived with their parents
122/
Key findings:
-high levels of very severe ME in kids age 0-19 (very severe ME is associated with childhood onset age 0-15 years)
-45% of very severe patients lived with their parents
122/
Very severe ME patients limitations:
-could say a few words about 3x week
-have a shower or get dressed almost never (big difference between severe and very severe)
-never tolerate sunlight from a sensory perspective (big difference between severe & very severe)
124/
-could say a few words about 3x week
-have a shower or get dressed almost never (big difference between severe and very severe)
-never tolerate sunlight from a sensory perspective (big difference between severe & very severe)
124/
Most troublesome symptoms (rated 0-5)
-fatigue 3.4
-muscle/joint pain 2.1
-brain fog 1.7
-sleep disturbance 1.6
-sensory intolerance 1.6
The sensory intolerance correlated with severity score.
125/
-fatigue 3.4
-muscle/joint pain 2.1
-brain fog 1.7
-sleep disturbance 1.6
-sensory intolerance 1.6
The sensory intolerance correlated with severity score.
125/
Now Dr. Tania Dempsey presenting on a case study of atypical presentation of Mast Cell Activation Syndrome and pericarditis in #MECFS
Prior to #MCAS diagnosis, infectious disease found Bartonella & EBV infections. Treated w/ IV antibiotics. Then pericarditis onset.
127/
Prior to #MCAS diagnosis, infectious disease found Bartonella & EBV infections. Treated w/ IV antibiotics. Then pericarditis onset.
127/
Symptoms: Itching/burning skin, brain fog, head heaviness, vertigo, food sensitivities, SOB and chest pressure, fatigue, and others
Lab findings: elevated histamine plasma, heparin assay, borderline elevated ANA and rheumatoid factor. Normal 24hr urine tests.
128/
Lab findings: elevated histamine plasma, heparin assay, borderline elevated ANA and rheumatoid factor. Normal 24hr urine tests.
128/
Note on heparin from Dr. Dempsey––there is no reason to have elevated heparin in blood unless the patient is on heparin, or unless they have Mast Cell Activation Syndrome.
129/
129/
MCAS should be considered in patients whose prior extensive evaluations "failed to find any evident disease better explaining the full range of findings" &
+ Physical exam
+ lab data consistent w/ chronic, aberrant mast cell mediator expression
+ response to intervention
130/
+ Physical exam
+ lab data consistent w/ chronic, aberrant mast cell mediator expression
+ response to intervention
130/
This patient fit MCAS consensus 2 criteria, specifically:
- Elevated Heparin
- Elevated Plasma Histamine
- Increased mast cells id'd in pericardial biopsy
- Response to H1 blocker with H2 blocker. "Heat feeling in body" and brain fog improved.
131/
- Elevated Heparin
- Elevated Plasma Histamine
- Increased mast cells id'd in pericardial biopsy
- Response to H1 blocker with H2 blocker. "Heat feeling in body" and brain fog improved.
131/
With further treatment of MCAS:
- Vertigo decreased by 80%
- Improvement in head pressure, reduced joint pain
- Pericarditis resolved (!)
- After 2 months of H1&H2 *significant* symptom improvement
Dr. Dempsey mentions this paper for MCAS treatments: ncbi.nlm.nih.gov/pmc/articles/P…
132/
- Vertigo decreased by 80%
- Improvement in head pressure, reduced joint pain
- Pericarditis resolved (!)
- After 2 months of H1&H2 *significant* symptom improvement
Dr. Dempsey mentions this paper for MCAS treatments: ncbi.nlm.nih.gov/pmc/articles/P…
132/
Now onto Dr. Rowe who is presenting on a case of #MECFS diagnosed w/ hypermobile Ehlers Danlos & CCI/AAI.
After fusion surgery (occiput - C2), headache & neck pain resolved. Head feels supported. No longer lightheaded on standing, cognition & processing improved. #MESpine
133/
After fusion surgery (occiput - C2), headache & neck pain resolved. Head feels supported. No longer lightheaded on standing, cognition & processing improved. #MESpine
133/
Dr. Rowe: Patient had much better energy & activity tolerance, including return to work part-time. Wellness score up to 80/100 (from 20/100 prior)
Ehlers Danlos syndrome put her at risk for CCI in combination with minor car accident and previous rock climbing activities.
134/
Ehlers Danlos syndrome put her at risk for CCI in combination with minor car accident and previous rock climbing activities.
134/
Now, Dr. Kaufman speaking: Oxaloacetate Supplementation Provides Hope for Fatigue Amelioration in #MECFS
Dosage 500mg or 1,000mg BID. Dramatic drop in fatigue even at 2 weeks, extending to 6 week mark. Higher dose = greater response. Patients had been sick 5-30 years (!)
135/
Dosage 500mg or 1,000mg BID. Dramatic drop in fatigue even at 2 weeks, extending to 6 week mark. Higher dose = greater response. Patients had been sick 5-30 years (!)
135/
80% of participants show improvement. This is remarkable, he says. Dr. Kaufman said patients speak of improvement in overall wellbeing & some describe brain fog improvement.
No significant adverse effects. 2 pts had reflux, resolved by taking w/ food.
136/
No significant adverse effects. 2 pts had reflux, resolved by taking w/ food.
136/
Oxaloacetate is a human energy metabolite. Fatigue continues to improve over time & w/⬆️ dosage. Oxaloacetate shown to be safe at levels 1000 mg BID in multiple clinical trials for other groups (ALS, Alzheimer's, Parkinson's)
⭐Dr. Kaufman's goal: funding for RCT for this
137/
⭐Dr. Kaufman's goal: funding for RCT for this
137/
Dr. Kaufman has been using 500mg oxaloacetate. (Online availability are lower doses.) Cost: $500-600 per month at higher dose.
He emphasizes they've had *zero* funding for this––he's been providing his time for free, & company providing supplement so far.
138/
He emphasizes they've had *zero* funding for this––he's been providing his time for free, & company providing supplement so far.
138/
In Q&A, patients asking numerous questions about Oxaloacetate––where to find, cost, etc. He says company they used is Terra Biological.
(Just saying––the above RCT on oxaloacetate would be worth funding ⬆️ Emphasizing again Dr. K has been doing this with *zero* funding👀)
139/
(Just saying––the above RCT on oxaloacetate would be worth funding ⬆️ Emphasizing again Dr. K has been doing this with *zero* funding👀)
139/
Question on CCI (cervical instability) in MECFS for Dr. Rowe: He says hypermobile Ehlers Danlos is low-hanging fruit & we need to assess for & study it, especially with younger onset patients w/ #MECFS. Some cases do not require surgery & can improve with physical therapy.
140/
140/
• • •
Missing some Tweet in this thread? You can try to
force a refresh
