Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome.

Observed Findings

• ME/CFS patients showed elevated neutrophils and monocytes with reduced lymphocytes compared to recovered individuals.
• Specific immune cell markers (2B4+CD160+ and TIM3+CD160+ CD8+ T cells) completely separated ME/CFS patients from recovered controls.
• Plasma levels of Galectin-9 and artemin were significantly elevated in ME/CFS, with artemin correlating with pain and cognitive impairment.
• Expansion of CD71+ immunosuppressive erythroid cells was observed in ME/CFS patients.
• Multiple autoantibodies were elevated in long COVID patients, suggesting autoimmune activation.

Inferred Conclusions

• ME/CFS represents a distinct immunological state characterized by T cell exhaustion, chronic inflammation, and immune dysregulation distinct from simple viral recovery.
• A multi-parameter immunological signature (including terminal effector T cells, artemin, Galectin-9, and reduced regulatory cells) could serve as a diagnostic biomarker for ME/CFS.
• CD71+ erythroid cells may play a pathogenic role by suppressing immune regulation while driving artemin production linked to neurological symptoms.
• Artemin and Galectin-9 may be mechanistically important in ME/CFS pathogenesis and represent potential therapeutic targets.

Remaining Questions