John Haughton MD, MS 🌻
@doc4care
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Health better for all. Geriatric Rehab Physician, payer, patient, engineer, family, friend. WorkFocus: #longcovid /inflammation #pophealth #riskadjustment /HCC
Annapolis, MD
Joined February 2011
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Thread attached about how the “confused” immune system drives covid / long covid and some things that can be done now to help reverse it.
#LongCovid
#Treatment
#Science
1/n - Easier way to see TLR4 impact from viruses (TLR4 generally reacts to LPS and causes inflammation in sepsis. Some viruses - 4 shown in this paper “turn o TLR4 too”. (The confusion talked about in immune response in Covid?) k
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Long Covid study shows TLR4 inflammation is at the core of the disease. Stop/Reverse to end the feedback loop causing ongoing downstream issues of inflammation and micro-clotting . Multi prong approach should work. Antiviral, TLR4 block, Fibrin break up, Probiotics… What Else?
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🔔14 days of metformin lowers viral load and decreases clinical risk in acute and long covid vs placebo. 42% to 58% lower risk. Paxlovid doesnt do that.
(Omicron variant, outpatient population. Likely via MTOR path).
🔔Makes sense to use metformin.
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1/2 Paper showing Metformin stops Spike driven inflammation. And shifts metabolism.
Metformin Suppresses Monocyte Immunometabolic Activation by
#SARSCoV2
Spike Protein Subunit 1
"SARS-CoV-2 spike protein induces a pro-inflammatory immunometabolic response in monocytes that can be suppressed by metformin"
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Is Covid “slow sepsis” and is Long Covid “chronic sepsis”? Thoughts?
Mitochondria article speaks to energy production & potential treatments to improve mito energy i sepsis. Mechanisms similar to LC/MECFS energy issues
TLR4 turned on by LPS in sepsis and by S1 spike in Covid
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@EricTopol
@CellCellPress
@SuezLab
@EranElinav
@segal_eran
@WeizmannScience
@Yot_Coh
@Elinav_Lab
Interpretation: using saccharin or sucralose (Splenda) decreases the body.s ability to control sugar (glucose) within desired ranges. Blood sugar goes up more after eating if one uses either of those sweeteners for a couple of weeks. It happens due to gut bacteria changes.
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Taurine and mitochondria and effectiveness in patients with impaired cardiac function, 2 articles: 1) overview 2) clinical trial with ~25% increase in exercise capacity and cardiac output after 2 weeks of 500mg 3 times a day of taurine.
#longcovid
#mecfs
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Antivirals with anti-sars capabilities:
We will finally know what works via trial for truvada.
Truvada = $20/mo
(and might work better)
Paxlovid = $1300 for 2 weeks.
Funded study of antiviral tx in long covid announced that tests truvada and will also look at marovirac
1. Icahn School of Medicine Mount Sinai: “A clinical trial of repurposed HIV antivirals in LongCOVID” 👉 Learn more here:
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Naproxen is antiviral for SARSCov2. As is Allopurinol. Ethyrinic Acid (diuretic) is even more effective.
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Metformin to improve CD4 exhaustion? Works to quiet inflammaging in Th17. Looks as if via pathway related to exhausted CD4 Tcells. Metformin enhances autophagy (recycling cell components) to limit inflammation. Looking at 30 to 60 y.o cells. Thoughts?
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Thread with explanation of immune system changes with viral attack. Uses a “beanbag” as immune system and “beans” as immune cells analogy that makes it easier to follow. Links to papers. Bottom line - we need to stop excess inflammation, it.s causing ongoing damage.
ALL VIRAL INFECTIONS damage the immune system driving:
- immune dysregulation
- aging of naive t-cells
- cellular senescence
- increased risk for autoimmune diseases (diabetes, Alzheimer's)
- oncogenic (cancer-causing)
- opportunistic susceptibility to secondary infections.
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“Reverse vaccine” tested in multiple-sclerosis-like disease & worked!
The team linked myelin proteins to pGal [for] the new inverse vaccine.
🔔The immune system stopped attacking myelin, allowing nerves to function correctly again and reversing symptoms of disease in animals.
University of Chicago: “A new type of vaccine developed by researchers at the Univ. of Chicago Pritzker School of Molecular Engineering (PME) has shown it can completely reverse autoimmune diseases—all without shutting down the rest of the immune system’
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@JReinerMD
Here is a link to a good summary of what happens with commotio cordis. quick defibrillation as others have said too, is key.
#hamlin
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Prescribing exercise in those with PEM is malpractice!
Very well said,
@PutrinoLab
(If no PEM (post exertional malaise) , exercise is ok.
The key to not harm is to stay in the acceptable energy use range that does not cause PEM
It’s dangerous and it’s intellectually lazy.
proud to have been included. it is about why (for the millionth time) GET should not be prescribed for
#LongCOVID
. Sorry not to tag all my amazing co-authors but my internet is spotty AF. Be well everyone 🙏🏻 /end
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Mayo study of
#longcovid
clinic ~2 yr followup. List of interventions that worked 50-80% of the time…
"Self-reported symptoms were all significantly improved (P < .001) from the initial visit to the LCC (baseline) to the time of the followup survey.However,only 4.5% (24/536) of patients rated all symptoms low (1-2) at the time of the survey,indicating low levels of full recovery"
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Let’s get a long covid lab test. Ang-1 and P-Sel together identify Long Covid.
Red = long covid. Green= healthy control.
In my opinion, ANG-1 and P-SEL should be a routine lab test for anyone suspected of possible Long Covid or Long Vax.
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Microclots stop blood flow.
Red in left picture below is what happens with the addition of SarsCov2 in small brain blood vessels.
And not only limiting flow, but adding lots of inflammation.
Treat inflammation + Break microclots = path to symptom reduction (in LC?).
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@MrkStdngr
And could be that “aging” is inflammation and senescent or “zombie cells” from post viral conditions as well as other things that cause hypoxia and inflammation. Hypoxia drives “HIF1a” into the nucleus of cells and it starts pushing out inflammatory cytokines, IL6 etc.
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NIH: ME/CFS is an infectious/immune driven BRAIN INJURY.
——————-
Results from a deep study of me/cfs patients and healthy controls.
Includes gut-brain access changes.
Lower heart rate variability is one trackable measure.
The long-awaited NIH Intramural Study of ME/CFS, led by Avindra Nath, has finally been published in full.
🧵 "Considering all the data together, Post-infectious ME/CFS (PI-ME/CFS) appears to be a centrally mediated disorder." 1/
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Brain fog impact:
Having covid drops IQ 3-9 points. Reinfecting drops 2 more.
It is like aging 7 to 20 yrs after a mild to severe infection.
Discussion of brain damage from covid from
@zalaly
.
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Treat inflammation now. Reverse
#longcovid
Lower TLR4 & RAGE action.
Get blood flowing, reverse hypoxia.
Break microclots.
Flip mono/macro M1 to M2.
Push TCA energy over glycolysis.
Limit viral replication
We’re all learning how, but these are lots of the “whats”
Patients with Long Covid show persistent unstimulated IFN-γ secretion, in keeping with their unremitting symptoms. Longitudinal follow-up showed that symptom improvement and resolution correlated with a decrease in IFN-γ production to baseline levels.
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Proteins at diagnosis show who gets long covid:
proteins were mostly coordinated around lipid, atherosclerosis and cholesterol metabolism pathways, complement and coagulation cascades, autophagy, and lysosomal function.
at diagnosis, associated w/ symptoms out to 12 months.
Future Perspektive: Targeting the HDL-Proteome for the treatment of postCOVID
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Strong evidence for anti-inflammatory affects of Curcumin. Review shows effectiveness for inflammatory arthritis. Also, it.s Cheap Safe and Effective. It acts on TLR4 (receptor that needs to be quieted in Long Covid). 2 articles.
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“Smoking gun” articles together re:brain fog
#longcovid
spike binds TLR4. TLR4 activation causes memory issues.
AND IS REVERSIBLE at least in mice! DrT post shows flow process.
There are lots of ways to quiet TLR4 activity (curcimin, metformin, berberbine, LDN etc)
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@MsClaire_Cotter
Some data showing up that 10mg or so of melatonin daily or split doses can impact viral replication by blocking ace2 and cd147. And lowers crp, Il6 and TNF. Not med advice, but latest info to do with what you and or your doctor want to do with it. From a few papers:
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Paper showing Berberine and impact on specific gut flora - animals and people. More “good”, less inflammatory flora. Increases gut short chain fatty acid (SCFA) which is a good thing for quieting inflammation.
@remissionbiome
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Long covid and mitochondria review.
The authors figured out root issues of
#longcovid
and the mechanism in 2022!
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What does Brain Fog look like (covid inflammation)? It’s real!
(Green stuff shows activated microglia/macrophages, red = astrocytes).
Right = covid inflammation in brain.
Left = no covid.
(Blood vessel and microglia inflammation due to covid).
@DaniBeckman
picture:
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Link to original study on long covid cause.
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Comprehensive
#longcovid
mechanism and treatment approach paper.
Useful clinical details.
Good links between symptoms and mechanisms and treatment approach - ones that can work now.
@remissionbiome
Paper out from
@LOCOMOTIONstudy
(including our Founding Member
@NikkiS_MCSFS
as co-author): ‘Pathophysiological Mechanisms in
#LongCovid
: A Mixed Method Systematic Review’.
Thanks to all involved in the hard work!
#TreatLongCovid
#CureLongCovid
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@resiapretorius
@dbkell
@doctorasadkhan
From preprint pretorius lab. Blood test values for LC vs Control. Many LC values at mid or high ref range. Alpha2 antiplasmin at 90 is above ref range. Clinical measures, finally! (Even if preliminary).
#longcovid
measurement
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This is wild. At least in cortical pyramidal neurons, Mitochondria can run in reverse USING ATP (not producing it)!! (Use ATP to maintain Calcium balance / membrane potential.
#mitochondria
#wondersofscience
We learnt at school that mitochondria have their own DNA and produce ATP ... but not in the axon of cortical pyramidal neurons! Wonderful results from
@fpolleux
@HirabayashiLab
. Wondering what are the underlying developmental and evolutionary mechanisms.
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More info on TLR4 blocking. Note - AceReceptor Blockers, Melatonin Prednisone and Berberine limit TLR4 activity as do Metformin and LD Naltrexone listed below. Pred example: . Berberine example: .
@baristabarb
@JoshuaPribanic
Interventions that down regulate TLR4 and increase NRF2 appear to be important in decreasing reactive oxygen species. As one of its effects, Metformin down regulates TLR4. Low dose Naltrexone is another TLR4 down regulator.
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Why taurine works -
A new vicious cycle involving glutamate excitotoxicity, oxidative stress and mitochondrial dynamics
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@thephysicsgirl
Once acute stabilizes, work toward lower inflammation in gut too and getting rid of the virus, if any left. Getting microbiome back to a balanced state, decreasing inflammation and also working on stopping potential microclots. Ok to DM if you want to. Good luck either way.
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🔔Me/cfs review from symptoms to treatment and clearly written.
Relevant for longcovid microvascular and immune issues too.
Clear mechanism description and figures.
Has specific pharmacological and non rx treatment.
Wow. What an effort. Thx to
#teamclots
Paper on the clinical presentation of ME/CFS, the current insufficient diagnostic criteria, potential disease triggers, and the complex pathophysiology of the condition. My fab PhD student Hayley Arron, 1st author with
@doctorasadkhan
@dbkell
@bendymarsh
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2/2 Some key graphs from the paper. Metformin really works against the spike. Blue = spike with metformin.
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Microclot paper hypothesis that LC may be associated with not clearing microclots lines up with inflammation increasing with Hypoxia via HIF1 balance. So
Blocked capillary makes hypoxia and creates inflammation (via HIF1 drive) which makes less 🩸 flow and more hypoxia a loop!
So a hypothesis is emerging that acute COVID might cause microclotting in the majority of people, but in some people with Long COVID the ability to clear the clots is defective. More research is needed to look at this 8/
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#remissionbiome
@remissionbiome
Jackson lab with detailed multiomics eval leading to evidence of butyrate down and tryptophan up in gut of those with long term mecfs. (Nih mecfs conf talk this morning)
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#hamlin
looks as if he took a helmet to the chest. There.s a split second during the electrical cycle of the heart where a a mechanical impact can cause the heart to go into fibrillation (vibrating, not pumping). Prayers that if this was it, that a defibrillator was there fast
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@WesElyMD
@netiamccray
@sealey_kf
@LisaAMcCorkell
@NASEM_Health
@patientled
@ahandvanish
@long_covid
@loscharlos
@IppoAng
@LongCovidScot
@LongCovidSOS
@C19LH_Advocacy
Re: effective therapies. One of the key items shown in the Nat Academy Long Covid meeting was CCL11 rise in the hippocampus (affecting memory). Mechanism similar to “chemo brain”. Metformin and Berberine both inhibit CCL11 and are available and accessible now. 1/n
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Accessible and accurate news story about a study showing inflammation in the gut affects the brainstem and changes the inflammatory balance.
🔔Root issue on lots of the fatigue/inflammation going on all around us.
Found: the dial in the brain that controls the immune system
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@j_corey02
@j_b_kennedy
Yes. It is effective and safe. Taken for 2 weeks at start of infection, it Lowers risk of long covid from 10% to 6%. When people start it, sometimes increases gas/gi activity.
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#Wasf3
induced by HIF1a and gums up mitochondria.
#HIF1A
goes up in hypoxia.
Blocking
#TLR4
limits HIF1 by balancing toward nuclear NRF2.
So, Care focus: Push from inflammatory M1 to building M2 wbc.
Break microlots.
Get oxygen flowing.
#longcovid
.
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Really well written and practical mast cell thread - includes issues and specifics for diet and control with links to more resources.
#mastcell
#histamine
#LongCovid
If you have mast cell issues, you’re gonna wanna learn about histamine in food. At this point I consider myself a mast cell specialist. I know the histamine levels of everything now. You want to stick with foods that are fresh, the fewer ingredients the better. Nothing frozen or
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If there.s someone reading this associated with Recover or other grant funding or LC/ME/CFS foundation consider reaching out to offer a stipend for the amazing survey work that
@organichemusic
created and executed.
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Profound change in MRI imaging. Injecting markers results in seeing within tissue changes energy metabolism, including lactate, bicarbonate, pyruvate. ? Use in showing improvement with treatment for long COVID / me/cfs. Trials underway. Can show heart attack damage etc.
"The technique is the outcome of more than six decades of supposedly arcane basic physics that many would have dismissed as being irrelevant and of no use to the “real world”"
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Inflammation and mitochondria impacting depression. Paper addressing situation, what goes wrong, impact and treatment
@ChrisPalmerMD
@remissionbiome
#MECFS
?
#LC
thx for posting,
@agingdoc1
Mitochondrial dysfunction: A fatal blow in depression
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Vitamin D replacement quiets inflammation caused by zombie (senescent) cells. Make sure you have enough!
Just published! My first last author paper! Showing that vitamin D inhibits inflammatory cytokine production from senescent dermal fibroblasts via inhibition of p38-MAPKinase pathway
@blizard_inst
@AkbarLab
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Link to the paper abstract showing 14 days of metformin lowers clinical risk and viral load in acute omicron covid outpatient treatment.
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@CarlosdelRio7
@dianaberrent
Example of sequential testing. Daughter (full vax and boost) travelled home for Christmas Mon. No symptoms. She masked while here. No symptoms until scratchy throat Wed. Neg test tues. Pic is Wed testing: super faint Wed at noon. Full pos Wed 9p.
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Article identifying a core, “Autocore” of genes that cross many inflammatory conditions. Adds evidence to base, core paths that get activated in different ways in different people with various auto immune and autoinflammatory conditions . 1/2
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4/n. So, treatment strategies that follow this path include:
1) Block TLR4 (curcumin, metformin, berberine etc);
2) Limit microclots and get blood flowining (H1, H2 antihistamines that lower MCAS + Nattokinase to break microclots +/- aspirin & clopidogrel).
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@Dakota_150
Too many Senescent cells (Zombie cells). Decrease inflammation, and disrupt zombie cells. Drugs that worked largely senolytics.
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Example paper showing Spike alone can cause thinking problems. And shows blocking TLR4 blocks the cognitive impairment from the spike.
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@ales_frost
Light / more energy = less inflammation. Lead / Heavy = more inflammation. Let there be light!
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Really clear and clinically actionable article from Mayo Clinic on Long Covid and ME/CFS. Labs to check. Approaches to specific symptoms. Useful for primary care. Enough detail. Differential Dx etc. Great for those in training or patients working with their doctors.
In Concise Review for Clinician's
🌟Diagnosis & Management of ME
🌟This is a good one to take to your HCP & to have in your toolkit
🌟States the ⬆️ in ME due to 50% of people with
#LongCovid
having
#ME
Text 👇
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Comprehensive article about endothelial cells and immune cells and glycolysis. Specific but readable.
Key area for
#LongCovid
HIF1a NRF2 balance via TLR4
HIF1a goes up in cytoplasm & moves to nucleus & causes activation, inflammation and glycolysis.
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There is evidence of antiviral activity for metformin too.
In addition to this work (preprint) in humans showing ⬇️ viral load with metformin there is also evidence in vitro of ⬇️ viral replication, possibly through an AMPK-mediated mechanism.
Important consideration not only for acute infection but also possibly for addressing viral
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~7 years from Sars1 to Parkinsons and Alzheimers in some survivors. Control inflammation now.
#TimeIsBrain
Autopsies found trace rna persistence. Link to microclots and ability to harbor other elements (including rna and other fragments - kell pretorius paper from this summer)
@joshfink429
@dbkell
@resiapretorius
Around 2010 we noticed a substantial increase of Parkinson’s and Alzheimer’s in SARS-2003 Survivors. Autopsies revealed trace RNA elements of persistent SARS viral persistence. As a “control” method we looked at other AD/PD patients, but found HCoV-OC43 traces.
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Any experience out there clinically with
#lactoferrin
in
#longcovid
#MECFS
Paper link to 2020 comprehensive review by
@dbkell
and
@resiapretorius
.
infographic = diff paper.
@remissionbiome
Lactoferrin antiviral and antiinflammatory properties.
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Elegant study by
@gibbological
and team: Higher butyrate production in the gut equals lowered inflammation, insulin resistance and LDL cholesterol in modeling study on microbiome. (Note - metformin among other interventions will increase SCFA (butyrate etc) in the gut).
Now, with some confidence in our MCMM predictions, we looked at blood-based clinical chemistries associated with SCFA-production across a large cohort (on a standard European diet). Butyrate was negatively associated with inflammation, insulin resistance, and LDL cholesterol.
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Clear Itaconate Shunt narrative. Thread by
@ahandvanish
of Dr. Ron Davis video. And Itaconate shunt turned on is M1 macrophage (killer, glycolysis) and turned off is M2 macrophage (builder, TCA). Increasing NRF2 moves to M2.
#pwME
#longcovid
But when the itaconate shunt happens, much of the cis-aconitate gets converted to itaconate instead, stealing it from the original cycle. This robs the body of the ability to make ATP (energy).
Then an enzyme, called CAD, gets imported into the mitochondria. 7/
#LongCovid
#pwME
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@organichemusic
interesting article on melatonin as a therapeutic for
#longcovid
. Can you include a melatonin try/efficacy question in an upcoming survey? Or if someone has tried melatonin for. LC with success or failure please share observations in this thread. Thx!
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Lowering inflammation with proven cheap, safe compounds… lots for TLR4 lowering (metformin, berberine, melatonin, curcumin, etc). DIGOXIN at low doses limits HIF1 directly!! (And no cardiac toxicity at low doses). Limiting HIF1, pushes toward TCA metabolism from Glycolysis. 1/2
@dbkell
@TeamPostX
@resiapretorius
So, clinically, if me/cfs and long covid is at least partially an issue of the shift to glycolysis and more limited TCA activity, then-since HIF1 tilts metabolism from TCA to glycolysis, limiting HIF1 should help and that happens by enhancing NRF2 and can be via limiting TLR4!
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@sumner_smith
@GeoEduOne
Natto should get at the fibrin breakdown side. You could look at both metformin and melatonin for anti-inflammatory and endothelial protective / stabilizing. The idea would be to slow formation as well as breakdown microclots. Not proven, but mechanism supported by science.
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Chronic inflammation - aging and long covid. RAGE / TLR4 - forces revving the immune system.
3 pictures -
1) macro
2) cellular
3) RAGE network
Lots here.
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In HIV, TDF/TAF slowed aging. abacavir increased it. So, insight for antiviral for long covid? TDF is about $20/mo U.S. it is approved for HIV prevention. Not aware on restrictions in who can get HIV prev in US. So, clinical path to cheap effective antiviral for those w/LC?
Transcriptomics age acceleration in prolonged treated HIV infection
@SystemsVirol_KI
& collaborators including
@jpsenescence
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#longcovid
potential: Study shows consuming 22 g freeze-dried blueberry powder (equal to 1 cup fresh blueberries) daily for 8 weeks leads to improvements in endothelial function in postmenopausal women.
Daily blueberry consumption for 12 weeks improves endothelial function in postmenopausal women with above-normal blood pressure through reductions in oxidative stress: a randomized controlled trial
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Taurine works in the mitochondria to neutralize reactive oxygen species indirectly by increasing SOD (also increases nrf2 in the nucleus, which generates antinflammatory outputs).
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2/2. Exercise capacity increased ~25% after 2 weeks of 1.5mg/day or taurine vs placebo. Small number of patients, 29. Heart failure. Also echo showed increased cardiac output.
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Thousands of viewers and the sharpest minds and experience in
#longcovid
#mecfs
. Congratulations on a job incredibly well done
#UniteToFight2024
So helpful to have the info shared in proximity to complementary data and experience. Thanks! 🙏
Organizing the
#UniteToFight2024
conference has been a challenging yet incredibly rewarding journey. Our amazing team of 5 individuals affected by
#LongCovid
&
#MECFS
poured their hearts and souls into the preparation, despite experiencing
#PEM
(Post-Exertional Malaise)
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Thought provoking.
Is this part of or THE explanation for metabolic switch seen in a small # of folks with LC/MECFS?
Happens minutes to hours. Fatigue goes away. Often for a short time. Some with longer energy flip.
Most commonly described w/ antibiotics
@remissionbiome
Should the standard model of cellular energy metabolism be reconsidered?
Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation
#MECFS
#LongCovid
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Many questions about Metformin and Berberine anti-inflammatory capabilities / mechanisms of action today after brain cell dopamine protection paper dropped. Discussion about same follows with link to a comparative paper with references
#longcovid
#sarscov2
@Mr_Inquisitr
@chydorina
Berberine shown to have similar effects as
#metformin
. Both increase gut short chain fatty acids. Both lower TLR4 activity. Both increase insulin sensitivity. They both move polarization from M1 (inflame and kill) macrophages to M2 (build). Link:
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And cost / safety is another plus:
14 days of metformin = $2-$20.
A course of paxlovid costs more than $1200.
$1000+ paid by medicaid, comm insurance, employer or medicare / MA:
🔔someone is paying the excess $1000+
And metformin has stronger efficacy data to support use.
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No Live Virus Needed to Drive Long Covid!
Zombie virus fragments mimic himan proteins and make zombie inflamed immune cells (senescent cells) which make ongoing zombie inflammation (chronic inflammation).
Quiet TLR ( toll like receptor) inflammation and start healing.
1/n
News Medical: '"Zombie" viral fragments trigger inflammation to cause serious COVID-19 outcomes'
The study was supported by the National Science Foundation, the National Institutes of Health, the Department of Energy and institutional funding sources..
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Microdosing GLP1 agonist (21ug/kg in mouse) had anti-aging effect similar to 8mg/kg of rapamycin every other day in mice.
Note - metformin in non-diabetics increase glp1 by about 20% after 6 months of tx
(multiple articles in thread below with more details).
Functional and multi-omic aging rejuvenation with GLP-1R agonism
🔎This, shared with me on
@LinkedIn
(where I accept connections with members of the longevity community under my name), by PI Owen (Ho Ko):
👉“Here, we conducted functional assessments and deep molecular
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Re: Covid/Long Coivd = Fast Aging
Re: Covid/Long Covid = Slow Sepsis
Via - (Cytokine, inflammation & increasing Toll Like Receptor 4 activity)
Study w/List of FDA approved drugs impacting aging
SGLT2, Metformin & GLP1 high on the list. Also, methylene blue, NAC and others.
Einstein researchers, led by
@NirBarzilaiMD
, evaluated
#FDA
-approved drugs for their anti-aging potential. In ranking those drugs, they gave equal weight to preclinical studies and clinical studies.
#aging
#ageing
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5/n Other additional approaches -
3) balance microbiome toward more butyrate/short chain fatty acid production (probiotics)
4) work on mitochondrial energy - shifting from glycolysis to TCA to make more ATP for the body. Ways to do it still evolving. Lower inflam + other?
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“In SARS-CoV-2 mouse model, prophylactic GlcN at a clinical-relevant dose significantly reduces the viral load in lung & trachea, and considerably alleviates lung inflammation”.
#viraltreatment
Oral administration of D-glucosamine confers broad-spectrum protection against human coronaviruses including
#SARSCoV2
#LongCovid
#MECFS
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@resiapretorius
@dbkell
Yes. system approach. Here is a draft approach to think about and treat
#LongCovid
that we are currently refining. Any comments / feedback appreciated.
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@zalaly
@SenSanders
@BillCassidy
HELP committee
#longcovid
- Jan 18: 1 patient panel and 1 clinician panel
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Sunday thoughts: Are fatigue and
#inflammation
of aging simply a later version of inflammatory
#longcovid
and
#MECFS
in younger folks? Is it the same process of inflammation and later on mitochondrial changes (and lower energy)? And is
#WASF3
a key? And does
#TLR4
drive it?
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More data showing key driver post acute:
Inflammation is quite commonly from auto-antibodies post acute phase.
More evidence quieting TLR4 should be helpful to let the immune system rebalance or slow if stays rev’d with autoantibodies
link:
Long Covid study shows TLR4 inflammation is at the core of the disease. Stop/Reverse to end the feedback loop causing ongoing downstream issues of inflammation and micro-clotting . Multi prong approach should work. Antiviral, TLR4 block, Fibrin break up, Probiotics… What Else?
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@healingfromlc
Both lipopolysaccride (LPS) and the spike protein activate TLR4 on cell surface. When both are present, TLR4 activity goes way up. So makes sense that getting rid of LPS by fighting sepsis could tip the balance from immune killer to immune builder status.
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Persistent viral particles (fragments, not growable virus) linked to ongoing symptoms in
#LongCovid
affecting the gut. 2022 article.
Postacute COVID19 is Characterized by Gut Viral Antigen Persistence in IBD; expression of SARSCoV2 RNA in gut mucosa ∼7mth after mild acute COVID19 in 32/46 patients with IBD. Viral nucleocapsid protein persisted in 24/46 in gut epithelium & CD8+ Tcells.
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Limit Toll Like Receptor in post infection inflammation! (Chronic inflammation needs to be quieted). ARB, Metformin, Melatonin, Low Dose Lithium, Low Dose Naltrexone, and other ways to make it happen).
News: Severe COVID-19 may lead to long-term innate immune system changes
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Looks like more evidence that treating
#longcovid
inflammation is a good idea.
A study of physical activity in >965,000 people (3 large cohorts) suggests that reduction of inflammation (INFLA-score) is the link to lowering all-cause death, CV and cancer mortality
preprint
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Interesting n=1 study. Tilt table test results. HR and SBP improved after H1 block tx.
#longcovid
#pots
#mecfs
“Complete remission with histamine blocker in a patient with intractable hyperadrenergic postural orthostatic tachycardia syndrome secondary to long coronavirus disease syndrom” full text
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Article includes a list of senolytics, with pathway and place of action. Relevant in breaking up “zombie” senescent cells spitting out inflammatory agents. Also speaks to cardiac impact in preclinical models
#LongCovidTx
#MECFS
fyi.
@remissionbiome
@MVGutierrezMD
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@EricTopol
@FT
@SarahNev
@federicacocco
Wondering how much of the excess seen in cardiovascular events is caused by covid related excess inflammation. So, is 1 in 12 with long covid vs controls (recent paper) a low # if controls have hidden inflammatory effects too. Either way 10.s of millions w/ongoing inflammation.
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@mor82397972
Heart stops. Then would take a few seconds until oxygen stopped getting to brain, so could stand up.
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Study: Itaconate drives anti-inflammatory change via Nrf2, driven by Acod1. Is iatconate shunt a physiologic response to ongoing abnormal inflammation driven by something else? Is the shunt the problem? Or both? Or depends? Nuance and detail affect lives.
#Mecfs
Happy to contribute (a little) to this one just published
@jclinicalinvest
. Congratulations Jianrui!
@LabGoldstein
@Gracedan10_99
@LyssiotisLab
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@Naomi_D_Harvey
Yes. And it may be that the infected monocytes become senescent “zombie” cells - putting out cytokines, not replicating and lasting awhile with viral remnants in them. And so, changing dynamics of autophagy and/or apotosis could jump start change/healing? (Last part not proven)
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@annatiscia
@erincandy
@tessfalor
@remissionbiome
Fyi.
First dose
#metformin
“switch” change in function.
Took berberine for a month first.
Similar reaction to Erin’s after taking taurine for a month before first dose of metformin.
Is this a switch from glycolysis to TCA?
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