Fighting Post-COVID and ME/CFS – development of curative therapies, 2023, Scheibenbogen et al

Sly Saint

Sly Saint

Senior Member (Voting Rights)
The sequela of COVID-19 include a broad spectrum of symptoms that fall under the umbrella term post-COVID-19 condition or syndrome (PCS). Immune dysregulation, autoimmunity, endothelial dysfunction, viral persistence, and viral reactivation have been identified as potential mechanisms. However, there is heterogeneity in expression of biomarkers, and it is unknown yet whether these distinguish different clinical subgroups of PCS.

There is an overlap of symptoms and pathomechanisms of PCS with postinfectious myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). No curative therapies are available for ME/CFS or PCS. The mechanisms identified so far provide targets for therapeutic interventions.

To accelerate the development of therapies, we propose evaluating drugs targeting different mechanisms in clinical trial networks using harmonized diagnostic and outcome criteria and subgrouping patients based on a thorough clinical profiling including a comprehensive diagnostic and biomarker phenotyping.

https://www.frontiersin.org/articles/10.3389/fmed.2023.1194754/full
 
In PCS, several interventional randomized controlled trials (RCT) have been initiated for targeted drug therapy worldwide (Table 1). This includes anti-inflammatory drugs, including corticosteroids, loratadine, montelukast, atorvastatin, baricitinib and phosphodiesterase inhibitors. Treatment studies depleting autoantibodies have been started with plasma exchange and immunoadsorption. The first specific drug in a clinical trial is the neonatal Fc receptor inhibitor efgartigimod, which enhances IgG degradation and was recently licensed for therapy in myasthenia gravis (28). Another study was initiated with the aptamer BC007, which has shown safety and GPCR antibody neutralizing capacity in a phase I trial (29).

Antivirals include targeting of potential residual SARS-CoV-2 as well as a monoclonal antibody against a reactivated endogenous retrovirus. Further several neuromodulators are studied in RCT, including vortioxetine, an antidepressant with established pro-cognitive properties, lithium with anti-depressive and anti-inflammatory properties, fampridine, a potassium channel-blocking agent linked to working memory and approved for multiple sclerosis, and dexamphetamine with first evidence for efficacy in ME/CFS (30).

Targeting endothelial dysfunction and hypoperfusion holds promise in both, PCS and ME/CFS, and a phase II RCT with the guanylate cyclase inhibitor vericiguat already licensed in heart failure has started in PCS and PC ME/CFS (31). Hyperbaric oxygen therapy (HBOT) was already shown to improve neurocognitive function in a phase II RCT in PCS, and is currently studied in another RCT (32).
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Sounds interesting.

Quote from the paper:

"Clinical trial platforms or networks would allow proof-of-concept clinical trials with various drugs in a harmonized manner using similar diagnostic criteria, evaluation tools, clinical outcome criteria and pre-enrolment phenotyping of patients to categorize them according to potential underlying mechanisms. Further clinical trial networks allow to rapidly recruit larger sample size when moving from phase II to phase III trials or to recruit ME/CFS patients triggered by another infection, e.g., EBV." [...] "Based on the concept outlined above, a German consortium was recently established, the National Clinical Study Group (NKSG) for PCS and ME/CFS."
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These are the drugs they listed as relevant to ME/CFS:
upload_2023-6-17_11-9-50.png
 
They discuss phase II trials of immunoadsorption, vericiguat, prednisolone and Hyperbaric oxygen therapy

The trials will be accompanied by a biomarker program. Basically, they will test a lot of things before and after the trials:

"neurocognitive and autonomic testing, multimodal MRI of the brain, as well as assessment of physical fatigue and endothelial dysfunction will be performed before and after treatment"​
 
Prof Scheibenbogen has been interviewed by Gez Medinger and Dr Asad Khan.

The talk is divided into 3 short duration YouTube videos uploaded in the last few days.

Focus on subgroups of LC including mainly MECFS, viral persistence, autoimmunity, clinical trials, bio markers, personalised care, etc

Link to first of videos:

 
Links to the 3 videos:
The Two Types of Long Covid (and the Role of Autoimmunity)
Video 12 minutes
Treating Autoimmunity in Long Covid & The Role of Viral Persistence
Video 13 minutes
How Long Will Treatment Trials Take? And Why is Research so Hard?
Video 15 minutes
 
ME/CFS Skeptic said:
The trials will be accompanied by a biomarker program. Basically, they will test a lot of things before and after the trials:
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I've been told the current platform consists of EndoPAT, RVA, fMRI, a belt test (something for endothelial function) and of course your blood results. So mainly things that look at endothelial dysfunction, which makes sense given their Vericiguat trials. OCT-A doesn't seem to be part of it yet, but maybe at a later point in time.

That being said the NKSG has no funding for next year (apart from donations) which could slow things down once again.
 
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