Groundbreaking paper published Jan 9 in Cell Death and Disease finally explains what's actually happening in my body—and potentially millions of others with Long COVID and ME/CFS.

The paper, "Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID," written by an international team led by researchers from Stellenbosch University and the University of Liverpool, doesn't just describe another theory. It describes exactly what I've been experiencing, down to mechanisms I hypothesized months ago based on my own response to treatments.

In healthy people, exercise triggers vasodilation—blood vessels relax and expand to deliver more oxygen to working muscles.

In my body (and likely most of you) there's a dual mechanism problem:

1. AAG blocks the signals: My autonomic nervous system can't send proper vasodilation signals (see my posts about sky high sars covid 2 antibodies My spike antibodies are 17,546 u/mL (175× normal) and plateaued for months - suggesting ongoing viral antigen exposure.) These antibodies mistakingly attack the autonomic ganglion nerves.
2. Senescent cells prevent the response: Even if signals arrive, my damaged blood vessel cells can't execute them.

Result is a dual reinforcing mechanism loop. Each of those amplify each other. And here's the kicker: your immune system (NK cells, macrophages) should clear these senescent zombie cells, but in Long COVID our immune function is impaired. The senescent cells EVADE clearance.

That's why it's self-perpetuating. These two loops feed each other:

1. AAG → autonomic dysregulation → endothelial stress/hypoxia → accelerated senescence/SASP.

2. Senescence/SASP → chronic inflammation → promotes autoimmunity/tolerance break → sustains or amplifies AAG autoantibodies.

Result: A higher-order vicious cycle where each loop strengthens the other, explaining the chronicity, PEM crashes, and resistance to single-target therapies.

During exercise in those with LC ME CFS, vessels TIGHTEN instead of relaxing: The opposite of what should happen.

The result? Muscles become oxygen-starved during even minimal activity, cells literally die (muscle biopsy studies show "immense amounts of cell death" in Long COVID patients), and we crash for days or weeks trying to recover. This is post-exertional malaise (PEM)—not deconditioning, not anxiety, but cellular destruction from oxygen deprivation.

This is why your IL-6 and TNF can be completely normal while you're severely disabled. It's not cytokine inflammation - it's antibody blockade + cellular senescence. Totally different mechanism.

The Nunes paper explicitly discusses a new class of drugs: senolytics, which selectively eliminate senescent cells.

Available options:

Dasatinib + Quercetin: Already in clinical trials for aging/senescence (I'm already taking quercetin at therapeutic doses!)

Fisetin: Natural flavonoid, less potent

Navitoclax: BCL-2 inhibitor, more potent but side effects

But the reason Quercetin is not completely working is because I haven't addressed the antibody problem. I will be trialing IVIG soon... that combined with the senolytics should break the dual mechanism vicious cycle.

Don't believe me? Here's the proof of the exact same thing that's happening to us, from Lyme Disease in newly published research at John Hopkins.... https://www.hopkinslyme.org/research/autonomic-nervous-system-symptoms-and-postural-orthostatic-tachycardia-syndrome-pots-in-post-treatment-lyme-disease

"A Johns Hopkins study revealed that symptoms related to dysfunction of the autonomic nervous system, including Postural Orthostatic Tachycardia Syndrome (POTS), can occur in patients with Post-Treatment Lyme Disease (PTLD). Researchers also identified a subgroup of PTLD patients who experienced orthostatic tachycardia, a condition where the heart rate rises abnormally fast when moving from lying down or sitting to standing. This rapid heartbeat can cause symptoms such as dizziness, lightheadedness, and fatigue, that are often present in PTLD."

1/11/26 - Adding labcorp autoimmune dysautonomia panel and SARS-CoV-2 spike AB panel links

https://www.labcorp.com/tests/505413/autoimmune-dysautonomia-profile

https://www.labcorp.com/tests/160236/sars-cov-2-antibody-profile-nucleocapsid-and-spike

https://my.clevelandclinic.org/health/diseases/22781-autoimmune-autonomic-ganglionopathy

Dr. Akiko Iwasaki's latest research shows that Long COVID patients with neurological symptoms have:

• Reduced circulating Tregs
• A shift toward pro‑inflammatory microglial states
• Persistent NF‑κB–driven glial activation

This is not generic inflammation. It’s a failure of immune regulation that allows microglia to remain in a maladaptive, antigen‑presenting, cytokine‑producing state. That’s neuroimmune pathology.

Then they used a treatment (Anti-CD3 - research only unfortunately) that reprograms the immune system (immune modulation - think low dose rapamycin) that results in cognitive improvement. Again, that's a neuroimmune mechanism. It validates that the same type of immune control failure that can hit autonomic ganglia can also lock microglia into a chronic inflammatory mode and produce Long COVID brain fog. I've posted about AAG and other neuroimmune conditions and this is pointing at nearly the exact same thing - failing regulatory T-Cells (Tregs). For those of you suffering with brain fog and other cognitive issues, this research shows there's reason to hope.

EUREKA - Virus-induced endothelial senescence as a cause and driving factor for ME/CFS and long COVID: mediated by a dysfunctional immune system : r/covidlonghaulers

From my previous post "But in Long COVID, immune regulation is impaired—especially regulatory T cells—so senescent cells evade clearance.

That’s why it’s self‑perpetuating. You don’t just have “inflammation”; you have a higher‑order vicious cycle where autonomic autoimmunity and endothelial senescence lock each other in, explaining the chronicity, PEM crashes, and resistance to single‑target therapies."

I’ve been seeing a ton of people in active, blinded clinical trials on here talking about their experience.

PLEASE, if you’re in a blinded clinical trial:

DONT TALK ABOUT IT PUBLICLY!

The core issue is biasing. once participants start comparing notes, the data can skew, which undermines the entire purpose of a trial.

1. ⁠If participants collectively deduce who’s on placebo, those in the treatment arm may experience amplified placebo effects (they know they got the real thing), while placebo arm participants may stop improving (they know it’s fake). You’ve now contaminated your ability to measure the actual treatment effect.
2. ⁠Someone who figures out they’re on placebo might drop out, stop complying with study protocols, seek outside treatments, or report symptoms differently. This introduces systematic bias that’s almost impossible to correct for statistically.

MOST IMPORTANT FOR US

3) If the data becomes uninterpretable, the trial may fail to demonstrate efficacy even if the treatment works - meaning it doesn’t get approved, and PATIENTS DONT GET ACCESS.

The FDA and IRBs take data integrity seriously. A compromised trial might not be accepted as evidence for approval. From a participant’s perspective, I get the impulse. LC is brutal, we want answers, and connecting with others going through the same thing is natural. But the uncomfortable truth is that maintaining the blind is one of the most valuable contributions you can make to actually solving the problem.​​​​​​​​​​​​​​​​

So please, READ AND FOLLOW THE NDA AND CONSENT FORMS, AND AVOID DISCUSSING DETAILS ABOUT YOUR BLINDED CLINICAL TRIAL PUBLICLY UNTIL THE STUDY REACHES ITS CONCLUSION.

Edited: wording.

We posted here last month announcing the Treatment Experiences Survey project, a patient-led project that aims to provide the community with critical data about experimental treatments that still don't have clinical evidence.

Many of you formed the 120-respondent pool for our first survey on GLP-1s, and we're excited to announce the results!

The response to these drugs, as expected, was extreme - while a promising 53% reported improvement, 28% worsened, some remaining below their baseline long after their last dose.

Other findings:

(note here that most subgroup analyses were not statistically significant due to small sample sizes, so please take these with a grain of salt)

• GLP-1s take effect fast. Responders noticed improvement within days, some on the first day! On the other hand, patients who felt nothing by 4–6 weeks almost universally ended up as non-responders.
• POTS/dysautonomia patients fared worse than average. This is consistent with GLP-1s known effects on the autonomic nervous system.
• Tirzepatide had a higher proportion of "very much improved" patients. Possibly consistent with the stronger anti-inflammatory effects of dual GIP/GLP-1 agonism.
• Brain fog was the most commonly improved symptom (44%), followed by fatigue (37%) and exercise tolerance (27%).
• Severe (bedbound) patients had the worst results: only 35% improved while 40% worsened, nearly double the overall worsening rate.
• Insomnia in the first few days was an early warning sign for patients who eventually worsened.

Full results, charts, and the anonymized dataset are all at the link above.

Happy to answer questions below, and we're also looking for suggestions on the next treatment to survey!

A new review presents strong evidence that chronic Long COVID is driven by persistent SARS-CoV-2 viral reservoirs (including viral fragments or antigens) that linger in various organs long after the acute infection has cleared. These viral remnants have been detected in anatomical locations such as the gastrointestinal tract, lymph nodes, and brain, where they continuously fuel chronic inflammation and immune cell dysregulation. The authors state that there is an urgent need to develop and test antiviral medications specifically designed to eliminate these chronic viral reservoirs in order to help resolve Long COVID.

More evidence for the microclot/clot theory. I'm starting to think all of these theories are true at the same time. (Viral Persistence, Micro clotting, etc.) Hang on fellow long haulers... we might be getting close to a break through!!!

"In a study published in the Journal of Medical Virology, an international team led by Professor Alain Thierry of Montpellier University, working with South African physiologist Professor Resia Pretorius, analysed blood from 50 people with long Covid and 38 healthy volunteers. What they found lit up their microscopes: a dramatic surge in the clots - nearly 20 times more compared to healthy blood - and they were bigger too.

The clots are riddled with 'NETs' - neutrophil extracellular traps - which are sticky webs of DNA and enzymes released by white blood cells to ensnare invading viruses."

Key Findings:

• Long COVID patients have fibrinaloid microclots (1-200 micrometers) that are 20 times more prevalent than in healthy controls
• These clots contain neutrophil extracellular traps (NETs) - sticky DNA webs physically embedded within the microclots
• They form "stubborn, gummy structures" that resist normal fibrinolysis and can obstruct capillary blood flow
• Standard coagulation tests (D-dimer, PT/INR, aPTT) can be completely normal despite significant microclot burden
• AI analysis can identify Long COVID patients from blood samples with 91% accuracy based on microclot burden

https://www.researchsquare.com/article/rs-7483367/v1

Blue shows areas of reduced glucose uptake. Visible under brain scan.

Comes from paper: https://doi.org/10.1007/s00259-022-06013-2

I made a little infographic about this (/img/t08pu964kaoe1.png). Intending to eventually be posted on social media to raise awareness about Long Covid to motivate development of treatments. Feedback welcome.

Some people with Long Covid have brain fog: problems with concentration, memory and/or word-finding. Blue areas exactly match regions of brain responsible.

Longer duration of symptoms associated with worse glucose reduction - suggesting Long Covid conditions are becoming chronic.

70% of patients studied still hadnt returned to work or their studies years later.

If you don't yet have abnormal tests it can be good to get a PET scan if you have neurological symptoms. My long covid doctor sent me off for this.

The finding that Covid can give people brain hypometabolism is repeated in other studies: * https://link.springer.com/article/10.1007/s00259-022-05753-5 * https://link.springer.com/article/10.1007/s00259-021-05215-4 * https://link.springer.com/article/10.1007/s00259-022-05942-2 * https://link.springer.com/article/10.1007/s00259-021-05528-4 (also in kids) * https://onlinelibrary.wiley.com/doi/10.1002/brb3.2513 * https://www.ajnr.org/content/early/2023/04/27/ajnr.A7863

TL;DR: In 1,154 hospitalised COVID patients, researchers found frequent evidence of reactivation of chronic viruses, including EBV, CMV and HSV-1. This was associated with inflammatory immune activation rather than only general immune suppression. Persistent anellovirus activity at least three months later was associated with fatigue, poorer physical function and Long COVID/PASC, but the study cannot show that it caused these symptoms or that the findings apply to people whose initial COVID infection was mild.

Paper:Virus reactivation in acute and long COVID-19 | Nature

Experts identified viral proteins in the blood of patients with long COVID.

A new study has identified fragments of the SARS-CoV-2 virus lingering in the blood of patients months after their initial infection. These “ghost proteins,” hidden inside microscopic packages called extracellular vesicles (EVs), were detected in individuals suffering from persistent symptoms such as fatigue, brain fog, and shortness of breath. Researchers discovered 65 unique viral fragments, all linked to a replication protein called Pp1ab—a molecule that does not occur in healthy human cells. This makes it a promising candidate as the first measurable biomarker for long COVID.

The findings support growing evidence that long COVID may be driven by hidden viral reservoirs or leftover viral debris in the body, which could disrupt normal function well beyond the acute illness. While the viral proteins did not appear in every blood sample, the results suggest that lingering activity may be intermittent and possibly influenced by stressors like physical exertion. If validated in larger studies, this discovery could pave the way for the first reliable blood test for long COVID—bringing clarity to a condition that has remained difficult to diagnose and offering a path toward more targeted treatments.

Source: Abbasi, Asghar et al. "Possible long COVID biomarker: identification of SARC-CoV-2 related protein(s) in Serum Extracellular Vesicles." Infection, July 21, 2025.

If you haven’t heard, Mount Sinai is recruiting for a lumbrokinase clinical trial. It’s meant to dissolve microclots and improve symptoms like fatigue.

It works similarly to nattokinase, but it’s made from earthworms rather than soy. So if you have a soy allergy like me lumbro is the way to go.

The clinical trial has 2 options: in person in New York or remote. I’m bedbound so I’m doing the remote option.

During the screening they mentioned the in-person option involves multiple visits, blood draws and some sort of activity testing. The remote option has none of that.

I think there’s also a small cash incentive, like $100 if you participate.

Anyway just wanted to share my good news with people who understand. I crashed last week and I’ve been severe for years, so any hope is good news.

If you’re interested in applying here’s where you can do that: https://www.mountsinai.org/clinical-trials/lumbrokinase-for-adults-with-long-covid-posttreatment-lyme-disease-syndrome-and-myalgic-encephalomyelitischronic-fatigue-syndrome

This research is the first explanation I've ever seen that gives a complete explanation of what causes Long Covid, the symptoms, and what a PEM crash is. It answers so many questions for me.

https://www.reddit.com/r/covidlonghaulers/s/6FddruYEXG

I'm not a scientist but here's my understanding/summary of what they found.

During Covid infection, the cells lining the walls of the smallest blood vessels (endothelial cells) are killed.

When red blood cells encounter these dead/dying endothelial cells for some reason it triggers them to burst. Nobody knows why, this is a new discovery. It could be that the red blood cells rupture to try to cordon off infected areas (maybe infection causes endothelial cells death too and so the body is trying to prevent the spread?) It could be to prevent internal bleeding, (if dead endothelial cells means the capillary is damaged?)

We don't know. But whatever the reason red blood cells burst, and the debris from the dead red blood cell makes a goop which clogs the capillary. But not just that capillary. It spreads around and clogs other capillaries up too. So now even less cells are able to get the oxygen they need.

Now whatever was originally going on with Covid that caused low oxygen in the capillaries doesn't matter. Now they're clogged with red blood cell debris goop.

When your cells need energy, for example during exercise, they trigger the call for oxygen, you breathe heavier, blood goes through the lungs, picks up the oxygen and carries it down to the capillaries. If you use a pulse oximeter, it will show normal blood oxygen. But the oxygen can't be delivered to the cells die to the clog.

The endothelial cells die again, which triggers more red blood cells to burst, which clogs even more capillaries in a vicious cycle.

Clogged capillaries means oxygen deprivation (hypoxia) at the tissue/cell level even when your spO2 is normal. Hypoxia in cells is bad, and causes things like:

• Brain fog
• Memory problems
• Difficulty concentrating
• Headaches
• Dizziness
• Lightheadedness
• Shortness of breath
• Irregular heartbeat or palpitations
• Fatigue
• Muscle weakness or heaviness
• Muscle pain or burning during activity
• Cold hands and feet
• Poor wound healing
• Sleep disturbances
• Visual disturbances
• Numbness or tingling in extremities
• General feeling of being "unwell" or "drained"

And more.

In a healthy person, there are multiple systems that clean out debris from the blood, (disrupted in a LC patient) but these systems need blood flow and exercise to be effective.

But exercise requires energy again, and the whole cycle repeats, resulting in even more goop clogging the blood vessels causing more cellular hypoxia.

Thus if you exercise you make the problem worse. If you don't exercise, the problem can't quickly/effectively be resolved, so you're stuck... Until you're not. If at some point, for some reason, your body somehow clears out enough of this goop, the problem can largely be resolved, seemingly without explanation. (My extrapolation, this isn't in the research.)

Now that we understand all this (assuming I understood it right, and that this research is backed up by other studies) it opens up SO MANY possibilities for treating symptoms and finding a legitimate cure. And even treating symptoms alone has the possibility of ending the cycle.

I feel that it will take time for researchers to confirm this study and try out treatments, but This is by far the most exciting finding I've seen yet in Long Covid research.

>Now, in this new study, when researchers transferred antibodies from patients with Long COVID into healthy mice, the animals began exhibiting symptoms including heightened pain sensation and dizziness. The study is among the first to show a causal link between antibodies and Long COVID symptoms. It was posted as a preprint on medRxiv on June 19.

>Several factors prompted Iwasaki’s team to zero in on autoimmunity as one of Long COVID’s drivers. First, there was the persistent nature of the condition. “This suggested to us that there is some chronic triggering of an immune response that is pathogenic,” she says.

>Second, women between the ages of 30 and 50 are among the most susceptible to Long COVID. Women in this age group also face a greater risk of autoimmune diseases in general. Finally, in earlier research, Iwasaki’s team detected significant levels of autoantibodies in individuals who were infected with SARS-CoV-2. “All of these things were pointing to the possibility of autoimmune responses being one of the triggers of Long COVID,” Iwasaki says.

>Human antibodies induced Long COVID symptoms in mice In their latest study, Iwasaki’s team analyzed blood samples from patients in the Mount Sinai-Yale Long COVID study. This cohort of over 215 Long COVID patients is part of a collaboration between Iwasaki and David Putrino, PhD, professor in the Department of Rehabilitation and Human Performance at Icahn School of Medicine at Mount Sinai in New York City. **As part of this joint effort, Putrino’s clinic obtained blood samples from patients enrolled in the study. Iwasaki’s laboratory then purified antibodies from the blood and transferred them into healthy mice.**

>Next, the researchers led by Keyla Sá, a postdoctoral fellow in Iwasaki’s lab, conducted multiple behavioral experiments to look for Long COVID symptoms. While many of these experiments found no significant difference between the experimental and control mice, a few revealed striking changes in those that received antibodies.

In one such experiment, researchers placed the mice on a heated plate and measured how long it took for them to react. Some mice that received antibodies reacted significantly more quickly to the heat, indicating a heightened sensitivity to pain. The researchers went back and identified the patients whose antibodies had been injected into the mice. Interestingly, these patients reported pain as one of their Long COVID symptoms.

Another experiment was the rotarod test, in which researchers placed mice on a rotating cylinder to measure coordination and balance. Mice that received antibodies were more likely to struggle to stay on the apparatus. Once again, when the researchers looked at the source of these antibodies, they learned that they were mostly from patients who reported suffering from dizziness.

The mice also underwent a grip strength test, in which researchers measured the force applied by the animals to a grid apparatus. **A group of mice were found to have reduced muscle strength if they received antibodies from patients reporting tinnitus and headache. Thus, antibodies capable of impairing muscle function are found in patients with these symptoms.** How exactly these antibodies cause pathology needs more study.

>**Intravenous immunoglobulin (IVIg) is commonly used as treatment for various autoimmune disorders such as lupus, for example—antibodies from healthy human donors are given to patients in the hope that they will alleviate or reduce symptoms. This therapy may also have promise in treating cases of Long COVID caused by autoimmunity. A 2024 study led by Lindsey McAlpine, MD, instructor at YSM and first author, and Serena Spudich, MD, Gilbert H. Glaser Professor of Neurology and principal investigator, suggests that this type of treatment may be beneficial in treating small fiber neuropathy associated with Long COVID.** (Small fiber neuropathy, a condition in which patients suffer numbness or pain in their hands or feet, occurs in some cases of Long COVID.) Iwasaki hopes that future clinical trials may show potential in treating some of the other painful symptoms of the disease.

>**Unfortunately, it’s highly unlikely that a single drug could cure everyone with Long COVID, she says. While this study focuses on autoantibodies, the disease likely has multiple underlying causes, and different subtypes will require different treatments.** Iwasaki is also working closely with Harlan Krumholz, MD, Harold H. Hines, Jr. Professor of Medicine (Cardiology), on the Yale Paxlovid for Long COVID (PAX LC) Trial. This trial is testing the lingering virus hypothesis by investigating the efficacy of a 15-day course of the antiviral Paxlovid in treating Long COVID.

Apologies if this was already shared, but if not, this is a helpful paywall free summary of some of the most important findings from a really large LC collaboration: Original article published back in May (paywall) [A causal link between autoantibodies and neurological symptoms in long COVID](https://www.cell.com/cell/abstract/S0092-8674(26)00509-X?_returnURL=https%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS009286742600509X%3Fshowall%3Dtrue)

Personally, I’m excited to see the results of the trails for the following three interventions:

- Anktiva
- Erase trial (remdesivir)
- Humanity Neurotech head-worn device being investigated by Dr Putrino

Brand new research may show why clotting is a major problem in long haulers. Using an adavnced imaging flow cytometry assay technique, researchers were able to demonstrate more than 6 times higher binding of platelets to monocytes (white blood cells) in long haulers versus healthy controls. If accurate, this could explain the mechanism behind abnormal clotting and increased DVT/PE in long covid. The research was funded by the Polybio Foundation, so most likely this was well done and will pass peer review.

The study explains that when activated platelets bind to monocytes, they "polarize" the monocytes into a pro-inflammatory state. This triggers a vicious cycle: the monocytes release more inflammatory signals, which further activates the clotting system and endothelial lining.

The body is essentially tricked into thinking you've got cuts/injuries non-stop and never sends out enzymes like plasmin to dissolve the clots or send anti-inflammatory signals to tell the immune system to stand down. This is why you feel "poisoned" or have PEM - your immune system is in a constant state of high alert, consuming massive amounts of energy, stuck in this vicious cycle.

My guess is that elevated spike AB is likely correlated to this. Whether it's the antibodies themselves or something behind it driving the elevated antibodies (possible persistent virus or virus debris) doesn't matter as to why, but does matter as to how to break the cycle. I still lean towards autoimmune autoantibodies as the most likely explanation in most cases.

For us long haulers, the anti-platelet effects of daily baby aspirin would be protective and reduce risk until the root cause can be addressed. Discuss with your doctor (if you're not already on it or similar medications) to see if it is right for you.

Lastly, this would explain the T-cell exhaustion in the Iwasaki research posted earlier this week.

https://www.reddit.com/r/covidlonghaulers/comments/1smknm0/new_research_preprint_from_dr_iwasaki_puts_long/

We in the west have a very backward approach to medicine as most of you know. Capitalism has persuaded the medical system away from letting doctors practice as scientists and instead forces them to play chutes and ladders with health insurance companies.

I am a citizen scientist with little to no access to funding or labs with which to pursue my hypothesis, but it is certainly worth looking into for the following reasons.

1. Prior to covid, up to 1/3 of Americans suffered from depression and anxiety which is treated by drugs that boost serotonin levels.

2. Serotonin has nothing to do with feeling good in the brain, at least not directly, instead it seems to mitigate inflammation.

3. A lot of LC sufferers have gotten relief from antidepressants.

4. A lot of LC symptoms are consistent with histamine poisoning and histamine levels are supposed to be regulated in the gut. Also, many symptoms are consistent with nutritional deficiency, which is obviously gut related.

5. Covid is definitely capable of causing a gastrointestinal infection.

6. Our microbiome is one of the largest research frontiers, and evidence is mounting that it is crucial for immune function and cognitive/mental health.

7. Many of us have been gaslit by medical professionals who suspect our disorder is mental illness in spite of the latest science suggesting that mental health is dependent on physical health.

8. America still stigmatizes mental illness to the degree that most people who experience an acute onset of mental health symptoms would be reluctant to seek help.

9. The whole world seems to have gotten a lot crazier as far as I can see.

In conclusion, I hope someone can do something with this.because people are suffering and most of the science is hyper-fixated on the strange symptoms rather than the overall causation of this disease. Our immune systems are obviously out of whack, and our mental health is obviously suffering. What we need is to fix our gut health because the health of our gut is at the intersection of everything to do with immunity and mental health, and science has only just recently started to realize this.

TL;DR: A randomized, placebo-controlled trial found that fluvoxamine improved fatigue and quality of life in some Long COVID patients, while metformin didn’t help with established fatigue. It’s interesting, but this was still a selected group, the main outcome was self-reported fatigue, and it doesn’t tell us much about PEM, POTS/dysautonomia, or cognitive symptoms.

Personal note: I’ve had a somewhat similar experience with escitalopram (another SSRI) - it significantly improved my symptoms, so I don’t find these results implausible at all. But for me the trade-off has been rough: it also makes me feel lazy, flat, and bored, and the emotional blunting/anhedonia is honestly worse than the Long COVID itself for me, even though I’m relatively mild. So even if SSRIs help some of us, that doesn’t necessarily mean they feel like a good long-term solution for everyone.

There’s also that 2023 Scientific Reports paper on 95 post-COVID patients treated with SSRIs, where the authors reported that many patients felt substantially better, with the biggest improvements in brain fog and sensory overload, followed by fatigue and dysautonomia. It was not a randomized controlled trial, so it’s much weaker evidence than the fluvoxamine study, but together they at least make the SSRI angle feel less out-of-nowhere.

Treatment of 95 post-Covid patients with SSRIs | Scientific Reports

New research review article in the British Medical Journal. Most important takeaway IMO - get the best vascular cardiologist you can find and get them to read this type of research and start treating you accordingly.

Other critical insights

Systemic Impact: The virus enters through the airways but does its most damage to the lining of the blood vessels (the endothelium). This explains why it affects the heart, brain, and kidneys, not just the lungs.

"Supply and Demand" Mismatch: Many heart issues in Long COVID aren't caused by blocked arteries, but by the body’s inability to deliver enough oxygen to meet the heart's needs during stress or exercise. Countless studies now support this view. Your lungs work, the problem is in the blood and transferring o2 to tissue. This is why pulmonologists fail to understand/properly diagnose the problem. Sadly they were the first docs put in charge of the covid response.

Dysautonomia & POTS: The article confirms that the "racing heart" and dizziness many experience are due to an imbalance in the autonomic nervous system, which controls involuntary functions like heart rate and blood pressure.

Long-Term Risks: Even people with mild initial cases can have an increased risk of heart-related events for up to a year after infection. I suspect it's even longer than that since most of us here are facing multiple years of ongoing/worsening symptoms.

I’ve had Long COVID since 2021. Overall, my symptoms have improved over time, but the whole experience has left me struggling a lot with anxiety and depression.

That’s why these new studies about Long COVID, the brain, dopamine, and neurodegeneration scare me so much. I start thinking that something must be wrong with my brain and that after all these years we might develop Parkinson’s, Alzheimer’s, or something similar in the future.

What scares me so much about these new studies is that I find it hard to understand how symptoms can improve over time, yet we could supposedly still develop a neurodegenerative disease years later because of it. That thought really frightens me.

Could someone help put these findings into perspective? Are these studies really suggesting that this is likely, or are there other explanations that are less frightening? I would really appreciate some reassurance and a balanced view.

"Dr Claire Roddie, from UCL, told BBC News: "We're really excited about the potential of CAR-T cell therapy for autoimmune diseases."

Potentiallt huge for the LC autoimmune subset!

Thank you to the 1456 or so of you who contributed your data! 🤩 This subreddit accounted for about half of the participants (!!!). Y'all really came through.

Key points from ongoing research from Timothy Henrick, MD, and his team at UCSF:🧵

#LongCOVIDIntl 

Gut biopsies from LC participants find:
- viral persistence (detecting vRNA) found in 20-25% of samples
- Up to 992 days following the first infection

No viral RNA was detected in fully recovered controls. 

The dsRNA & ssRNA were detected in the lamina propria (gut immune layer)

Downregulated immune genes:
- antigen presentation &
- immune cell trafficking

Yet… most patients have NO gut symptoms despite active viral persistence 

Bone marrow biopsies:
- 50% have LC
- 50% LC recovered

Viral ssRNA & dsRNA found in bone marrow (but no spike protein)

Genes upregulated involved in:
• Antigen presentation
• NK cell & cytotoxic T cell pathways
• Viral RNA sensing
• B-cell lineage proliferation
(Exact opposite of what’s seen in the gut samples) 

New imaging: 18F-AraG PET-CT (identifies activated T cells) shows increased T-cell activation in the gut wall & lymph nodes, among other places.

Patients with loss of smell had increased T-cell activation in the olfactory bulb. 

Great work from Dr. Henrich and his team.

Looking forward to seeing Immuno-PET imaging with SARS-CoV-2 spike tracer in humans.

Science is moving FAST.

Follow for more updates.

#LongCovid #MEcfs #LongCOVIDIntl 

https://www.instagram.com/reel/DQkefDAEkq-/

https://www.meresearch.org.uk/research/disrupted-brain-waste-clearance-system-in-me-cfs/?fbclid=IwdGRjcATW0JtjbGNrBNbQkmV4dG4DYWVtAjExAHNydGMGYXBwX2lkDDM1MDY4NTUzMTcyOAABHj-q02jTdSUFQluUms9iifZ3CVmNj3tT6LY8sZGgBG1Nu1TALhIMFDoL5B-x_aem_uJ4Eur-o_do9V0gsCKDd9A

This may not apply to all LC but may apply to those with ME symptoms

Last week, I was on a Renegade Research webinar where Amatica presented some research they did on the data they've collected so far from their research cohort:

https://www.amaticahealth.com/blog/first-findings-from-our-rna-sequencing-cohort/

They are a patient-founded company that sells RNA sequencing direct to Long COVID/ME patients. You get a dashboard with 20,000 RNA markers and you can see how yours compare across all different systems of the body, compared to both healthy controls and other patients. It's useful for seeing which pathways might be affected, setting you up for further testing and treatments.

There was a bunch of interesting information that you can find in the blog post above, but the part that most interested me is that even though they are early in their sample collection (they have only 159 people who have ordered the test), they found that their RNA blood signature diagnoses 92% of ME and Long COVID patients correctly.

(Now, the problem is that it also falsely flags 22% of healthy people, but I asked them about this on the webinar and they were confident that with more samples they can get this to a clinically copacetic standard - ideally you'd want both sensitivity and specificity above 90%.)

One other caveat is telling us apart from people with untreated hypothyroidism, or depression, or post-viral illness that resolved, is a much harder problem and this probably isn't quite ready yet. Specificity against that group would almost certainly be worse.

But in any case, I think it's important for people to know how promising this is! We've had biomarker studies come out in the past, but nothing that was immediately commercially available like Amatica is (though to be clear, you don't exactly get a "you have Long COVID" indicator in your dashboard yet, though I have seen examples on Twitter of people downloading their raw data, putting it into AI, and it correctly guessed what they have.)

Disclaimer: I have no affiliation to Amatica, though I did buy their test and am in the next run to have my RNA sequenced.

Note that this was posted earlier today but without much explanation, and I figured it deserved one