Insights on Postinfectious ME/CFS Save

The medical community is challenged by myalgic encephalomyelitis/chronic fatigue syndrome, or ME/CFS - its origins, pathogenesis outcomes and treatment.  JAMA has reviewed a recent Nature paper wherein an NIH led team of multidisciplinary experts performed an inpatient study of postinfectious ME/CFS patients.

Lead investigator, neurologist Avindra Nath, MD, claims that "ME/CFS is unambiguously biological", systemic with multiple organ systems affected,” and they "deserve to have their experiences taken seriously.”

ME/CFS has previously been labeled as chronic fatigue syndrome, myalgic encephalomyelitis, fibromyalgia or more recent, long COVID.

As ME/CFS was initially thought to be connected to Epstein-Barr virus and since, its onset has been linked to other viral or bacterial infections. For the CDC study, the core symptoms needed for a diagnosis include: 

• a reduced ability to do regular activities > 6 months
• serious fatigue that doesn’t improve with rest
• postexertional malaise
• unrefreshing or disrupted sleep

Other symptoms may include difficulties with memory or thinking, orthostatic intolerance, headaches, muscle pain, and shortness of breath.

The NIH study screened more than 200 people with possible ME/CFS, from whom 27 people were evaluated at the NIH Clinical Center and 17 were diagnosed with postinfectious ME/CFS. These were admitted to the NIH and underwent extensive testing. The ME/CFS group were compared to 21 healthy volunteers (control group).

Distinctive features of the postinfectious ME/CFS group included:

• Immune system differences. Naive B cells were increased and switched memory B cells were decreased in their blood, suggesting chronic antigen stimulation. Programmed cell death 1 (PD-1), a marker of immune exhaustion associated with chronic infection, was increased on CD8 T cells in their cerebrospinal fluid.
• Fecal microbiome changes. Their stool samples had less microbial diversity.
• Reduced neurotransmitter metabolism. Dopamine metabolites were significantly lower in their cerebrospinal fluid, in association with worse motor performance and cognitive symptoms
• Autonomic nervous system dysfunction: resting heart rate was higher, while their drop in nighttime heart rate and their ambulatory heart rate variability were both lower.
• Impaired cardiorespiratory performance. During an exercise test, their peak heart rate and aerobic capacity were both lower; after exercise they had a diminished cortisol response.
• Differences in performance on handgrip tests - which correlated on imaging with decreased activity in the brain’s right temporal-parietal junction, which the researchers believe could explain mismatches between desired action and resulting movement.
• “psychiatric disorders were not a major feature in this cohort and did not account for the severity of their symptoms.”
• ME/CFS patients performed normally on neurocognitive tests, despite having more cognitive symptoms.

The authors hypothesize that an infection causes lasting changes in the immune system and gut microbiome, possibly driven by the pathogen’s persistence in the body. These changes affect the brain, leading to a decrease in neurotransmitters that alters the autonomic nervous system and, ultimately, reduces cardiopulmonary capacity.

The authors suggest that people with ME/CFS should be treated for their symptoms, even if cause or pathophysiology for ME/CFS is unclear. ME/CFS patients may need to see a neurologist, a psychiatrist, cardiologist, pain management, multidisciplinary clinics, or long COVID clinics.