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

May 26, 2024Journal of autoimmunity

Different immune problems, ongoing inflammation, and reduced red blood cell production in long COVID patients with chronic fatigue

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Abstract

Patients with long COVID (LC) exhibited elevated levels of Galectin-9 and artemin, which are associated with debilitating symptoms.

ME/CFS patients showed increased neutrophils and monocytes but reduced lymphocytes compared to recovered patients.
Selective exhaustion of T cells was observed, with decreased naïve T cells and increased terminal effector T cells in ME/CFS patients.
Elevated plasma levels of pro-inflammatory cytokines, chemokines, Galectin-9, and artemin were associated with long COVID.
A specific concentration threshold of Galectin-9 and artemin strongly correlated with the presence of long COVID.
The expansion of immunosuppressive erythroid cells may influence immune responses and contribute to increased artemin levels, correlating with pain and cognitive impairment.
Distinct frequencies of certain CD8 T cell subsets separated long COVID patients from those who had recovered.

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A substantial number of patients recovering from acute SARS-CoV-2 infection present serious lingering symptoms, often referred to as long COVID (LC). However, a subset of these patients exhibits the most debilitating symptoms characterized by ongoing myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS). We specifically identified and studied ME/CFS patients from two independent LC cohorts, at least 12 months post the onset of acute disease, and compared them to the recovered group (R). ME/CFS patients had relatively increased neutrophils and monocytes but reduced lymphocytes. Selective T cell exhaustion with reduced naïve but increased terminal effector T cells was observed in these patients. LC was associated with elevated levels of plasma pro-inflammatory cytokines, chemokines, Galectin-9 (Gal-9), and artemin (ARTN). A defined threshold of Gal-9 and ARTN concentrations had a strong association with LC. The expansion of immunosuppressive CD71erythroid cells (CECs) was noted. These cells may modulate the immune response and contribute to increased ARTN concentration, which correlated with pain and cognitive impairment. Serology revealed an elevation in a variety of autoantibodies in LC. Intriguingly, we found that the frequency of 2B4CD160and TIM3CD160CD8T cells completely separated LC patients from the R group. Our further analyses using a multiple regression model revealed that the elevated frequency/levels of CD4 terminal effector, ARTN, CEC, Gal-9, CD8 terminal effector, and MCP1 but lower frequency/levels of TGF-β and MAIT cells can distinguish LC from the R group. Our findings provide a new paradigm in the pathogenesis of ME/CFS to identify strategies for its prevention and treatment. + + + + + +

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

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