ME/CFS Research Published 26 December 2023 – 1 January 2024

The weekly research round-up includes recent publications about ME/CFS and Long Covid. We highlight studies that have particularly caught our attention.

RESEARCH INDEX

The ME Association maintains a comprehensive index of published research on ME/CFS and Long Covid that is free to use and updated weekly.

VIEW THE ME/CFS AND LONG COVID RESEARCH INDEX

Audio Commentary by Dr Katrina Pears

It’s been a surprisingly busy week for research, despite it being the Christmas period. There has been a huge variety in the studies this week, with ten new ME/CFS studies and twenty-seven new Long Covid studies. Unfortunately, numerous studies this week appear to be behind a paywall.

We have also included the ME/CFS references for the previous week, 18-26 December 2023, where there were four new studies published.

We have highlighted one of the ME/CFS studies in more detail below:

Paper two (2) looks into the immunological dysfunction in ME/CFS and Long Covid and treatment with a nebulized antioxidant/anti-pathogen agent. The study included 12 patients with ME/CFS, 8 with Long Covid and 10 healthy controls.

The researchers firstly assessed the CD8 T cell dysfunction by developing a functional assay by intracellular cytokine staining (ICS). They also assessed symptom severity through questionnaires which were developed for the purpose of this study. These were then combined to assess the response to the treatment provided in a subset of patients (4 ME/CFS and 4 Long Covid).

CD8 T cells are lymphocytes, that are an important arm of the antiviral immune response. They kill virus infected cells and produce antiviral cytokines, they contribute to resisting primary and secondary infections.

The treatment used was a nebulized antioxidant/anti-pathogen agent, Inspiritol. It was initially developed to treat major symptoms of respiratory distress through an agent with combined antioxidant, anti-inflammatory, and broad-spectrum antiviral, antifungal and antibacterial properties. It is a sterile isotonic pH-balanced liquid suspension with four ingredients: two endogenously produced compounds (glutathione and methylcobalamin); one repurposed prescription drug that is a pro-drug to an endogenously produced amino acid (N-acetylcysteine); one plant extract monoterpene cyclic ether (1,8-cineole) and one natural bicyclic sesquiterpene (β-caryophyllene), in a proprietary liquid carrier. 

The ingredients have been reported to relieve oxidative stress, attenuate NF-κB signaling, and/or to act directly to inhibit pathogens, including viruses. These well-studied antioxidants and agents with anti-pathogen potential were administered to the lungs; components of this nebulized agent are also likely to be distributed systemically, with potential to enter the central nervous system.

Some of the key findings:

Both Long COVID and ME/CFS are characterized by dysfunctional CD8 T-cells with severe deficiencies in their abilities to produce the cytokines, IFNγ and TNFα.
The results showed CD8 T-cell dysfunction indicative of some aspects of T-cell clonal exhaustion, a phenomenon associated with oxidative stress.
The symptom severity questionnaire showed similar symptom profiles for both ME/CFS and Long Covid.
For the patients that underwent treatment, patients' immune deficiency and health improved during the treatment period with the nebulized agent.
For the patients that underwent treatment, there was an increase in CD8 T-cell IFNγ and TNFα production and a decrease in overall self-reported symptom severity score by 54%.
All 8 patients had a positive response.
No serious treatment-associated side effects or laboratory anomalies were noted in these patients.
The authors suggest that this work provides evidence of a useful biomarker, CD8 T-cell dysfunction reminiscent of T cell exhaustion, that may assist diagnosis and have utility for tracking disease outcome during therapy, including response to a potential new treatment.

There are some interesting results in this study, which further show the similarities between ME/CFS and Long Covid. A few further things to point out about this study:

ME/CFS was diagnosed by the Institute of Medicine Criteria.
This study was primarily a retrospective case series report and details the 8 patients who received the treatment (nebulized agent). Detailed patient characteristics and descriptions of 1 ME/CFS and 1 Long Covid patient are listed within the study.
Patients took the nebulized agent for different periods of time, dependent upon the rate of improvement in symptom severity. This varied from 3 to 15 months.
A further subsection of the patients receiving the nebulized agent also took an antiviral treatment, such as valacyclovir (VLX), valganciclovir (VLC), spironolactone (SPLT). Meaning it is difficult to truly compare patients.
The results show that intervening with Long Covid patients in the earlier stages of illness has a great potential to improve the disease course, compared to those with later stages or more chronic ME/CFS.
Some previous information on the research of the nebulized agent, Inspiritol, can be found on the Science for ME forum (here).

This is expressed by the authors to only be a preliminary study. The treatment suggested alone would need significantly more studies, which would need to be conducted in double-blinded controlled trials. This is also one of the few studies where biological measures are used to assess treatment response.

ME/CFS Research References