u/Caster_of_spells

Retinal vasculature is like a window into the brain because the eyes and the brain share the same system.

In this study changes were detected that weren’t too different from MS in LC patients.

In PCS, three layers were significantly thinner. pRNFL (nerve fibre layer around the optic disc), GCIP (ganglion cells plus their synaptic layer), TMV (total macular volume). And the worse the symptoms, the thinner the tissue!
Neuroretinal tissue is being lost - and it scales with how sick the person is.

This exact pattern - pRNFL and GCIP thinning - is an established marker of axonal and neuronal loss in multiple sclerosis, where OCT is used as a proxy for what’s happening in the brain

The group around Putrino has successfully completed their first mitochondrial transplant in a patient with vision loss after a brain bleed with the help of other experts in the field.

This should pave the way to trialing mitochondrial transplants in Long Covid and ME which Putrino already has plans on trialing.

“Also, there are so many conditions that can benefit from this work - including other forms of brain injury and neurodegeneration, but also #LongCOVID, #MECFS and other complex chronic illness where energy limitation is a problem. We will be aiming to get an active research arm off the ground on this ASAP.”

Source: https://bsky.app/profile/putrinolab.bsky.social/post/3msqs6xrgkc2i

New brain MRI study which induced hypoxia (too little oxygen) to compare reactions in the brain of patients to controls.

Interestingly lactate levels were already elevated at baseline in patients. Under hypoxia conditions controls started to produce more lactate to match while ME patients levels stayed at the elevated levels they were already at.

Roughly lactate is a byproduct of the less efficient way our system produces energy when oxygen is lacking (though its role in the brain is more complex than just that).

In the German CoCo-Fakt study at Cologne and Ausberg, patients who later developed Long Covid reported doing more and more intense physical activity prior to infection than controls who had COVID-19 but no long term symptoms.

The researchers expected the opposite.

The paper concludes:

"Unexpectedly, participants with long-term symptoms reported a longer PA [physical activity] duration in the four weeks before quarantine than those without long-term symptoms, albeit with a trivial effect size."

Results:

COVID-19 infection was associated with significantly increased hazard ratios for all six allergic conditions in the full cohort. Among the active-duty subset, asthma and rhinoconjunctivitis were significantly associated with infection. In children, all conditions except food allergy were significantly associated with infection

"Our most novel results relate to the lack of neuromuscular adaptation in ME/CFS compared to the [Healthy Volunteers]."

“Highlights

•We studied physical fatigue in patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and healthy volunteers with multimodal neuroimaging.

•Participants performed a fatiguing grip force task in alternating grip and rest blocks.

•We simultaneously recorded grip force, brain activity with functional magnetic resonance imaging and electroencephalography, and muscle activity with electromyography.

•ME/CFS fatigued earlier than healthy volunteers. While healthy volunteers increased their brain and muscle activity, ME/CFS only showed minimal fluctuations across all the task blocks.

•We concluded that physical fatigue in ME/CFS is of central nature.”

(Central in this context means: mediated via the brain. Participants brains didn’t seem to signal muscles sufficiently to ramp up energy production in response to demand)

A new study identifies two promising biomarkers:

•GDF-15, a marker of mitochondrial stress
•and VCAM-1, a marker of vascular endothelial injury

As predictors for developing Long Covid. Patients whose symptoms persisted for at least 6 months maintained significantly higher levels of both markers, despite having little evidence of ongoing systemic inflammation.

So what we see is not based in high level inflammatory markers—but in signatures of cellular energy failure and vascular injury may lie the answer for predicting long term outcomes in Long Covid.

Long Covid patients continue to have elevated counts of highly activated CD8+ T cells targeting viruses like SARS-CoV-2, CMV and EBV.

That is suggesting the antiviral killing response failed to switch off after the acute infection is over and might be part of the pathogenesis of Long Covid.

New Wüst paper!

•Results and Discussion

HRV was lower in patients with long COVID compared with healthy controls during various daily activities and sleep (p = 0.027). Across all exercise intensities surrounding the VT1, HRV remained lower for 24 h in patients compared with controls (p = 0.010). Nighttime HRV decreased with intense exercise and longer durations in patients with long COVID (p = 0.018), indicative of exercise-induced diurnal disturbances of the autonomic nervous system in long COVID.

•Conclusion

Heart rate variability, assessed by wearables, suggests autonomic dysfunction in patients with long COVID. The delayed recovery of the sympathovagal balance after exercise close to and above VT1, suggests that the risk of PEM rises above VT1.

Review preprint on neuroinflammation in Long Covid

“Post-COVID-19 syndrome (PCS) is an escalating global health concern, marked by persistent cognitive, neurological, and psychiatric symptoms following acute SARS-CoV-2 infection. Although its underlying mechanisms remain incompletely understood, mounting evidence implicates chronic neuroinflammation as a key driver. Sustained microglial and astrocyte activation, blood-brain barrier disruption, and aberrant cytokine signaling contribute to prolonged immune dysregulation within the central nervous system”

1. TAME – CD19-targeted B-cell therapy for post-infectious autoimmune ME/CFS using the monoclonal antibody tafasitamab: open-label follow-up study to a randomized, placebo-controlled Phase II trial of the CD19 antibody inebilizumab
   Principal investigators: Prof. Dr. Carmen Scheibenbogen & Dr. Judith Bellmann-Strobl 

2. Genetic Determinants of Post-Infectious ME/CFS: a 50-Family Study
   Principal investigator: Prof. Dr. Nataliya Di Donato

3. STRAT4PAIS — Immune Endotypes of Paediatric Post-Acute Infection Syndromes (PAIS): Mechanistic Stratification of ME/CFS and Related Post-Infectious Conditions
   Principal investigators: Prof. Dr. Marc Nikolaus & Fabian Dannenberg & Prof. Dr. Tilmann Kallinich & Dr. Mir-Farzin Mashreghi

4. Molecular dissection of cell death-mediated inflammation as a driver of virus-induced ME/CFS
   Principal investigators: Dr. Gregor Ebert & Dr. Stefanie Bader 

5. Myoflame-19 Autoimmune Substudy: GPCR Autoantibodies as Mechanistic Biomarkers of Endothelial Dysfunction in Post-COVID ME/CFS
   Principal investigators: Prof. Dr. Valentina Puntmann & Prof. Dr. Eike Nagel

6. Analysis of T-cell and B-cell receptor repertoires via single-cell RNA sequencing in patients with ME/CFS and post-COVID syndrome
   Principal investigators: Dr. Katja Schmidt & Prof. Dr. Thomas Harrer

7. MARK-ME – Minimal Biomarker Panels for Diagnosis and Stratification of ME/CFS
   Principal investigator: Prof. Dr. Birgit Sawitzki

Interesting new study theorizes that increased IL-11 and MMP-9 levels in ME patients could be due to mast cells reacting to EBV fragments.

“There was a significant increase in serum levels of IL-11 and MMP-9 in ME/CFS patients compared to control subjects. MCs stimulated by rEBV protein released a high amount of MMP-9 compared to control cells. In conclusion, IL-11, MMP-9 and MCs may be involved in ME/CFS individuals.”

King’s College London, 38 people.

Serum from those with worse post-COVID fatigue triggered stronger IL-13 and reactive astrocyte signals in human hippocampal cells.

What actually caused this? At first it looked like IL 8, but if you remove that from the equation the effect still stands. The authors put it carefully - mechanisms beyond IL-8 likely contribute.

All in all: serum clearly does something to brain cells ramping markers of neurogenesis and astrocyte activation. What exactly causes this remains a little unclear. Might be caused by the smaller sample size or even be a marker that simply wasn’t in their panel.

The BPS championed theory that cortisol and related stress levels prior to infection prime for chronic fatigue syndrome is officially dead:

“Preinfection hair cortisol concentration did not predict chronic fatigue six months after acute EBV infection. Elevated preinfection hair cortisol may reflect stress-related vulnerability to infection, and the shifted from a positive to a negative association over time, suggests that HPA-axis alterations are more likely a consequence rather than a cause of chronic fatigue.”

Simmaron Research, 76 people with ME/CFS.

After 90 days of low-dose rapamycin, fatigue and PEM improved as IMPDH2 activity fell, oxidative purines dropped, and mitochondrial reserve recovered.

No placebo group tempers the result.

Good to see them investigating the possible mechanism of action in low dose Rapa

Might be interesting to watch along to see wether the Amatica Cohort is actually turning up something of significance. So I thought I’d share it here for anyone interested! If you have thoughts do share in the comments