Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome, 2024

Diverse immunological dysregulation, chronic inflammation, and impaired erythropoiesis in long COVID patients with chronic fatigue syndrome
Saito; Shahbaz; Osman; Redmond; Bozorgmehr; Rosychuk; Lam; Sligl; Cohen Tervaert; Elahi

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 naive 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 CD71+ erythroid 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 2B4+CD160+ and TIM3+CD160+ CD8+ T 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.

HIGHLIGHTS
• This study specifically characterized LC with ME/CFS.

• We demonstrated that Galectin-9 and artemin are associated with ME/CFS in LC.

• This study links Galectin-9 with immune dysregulation in LC.

• We define CD71+ erythroid cells as a source of artemin in LC.

• This study advances our understanding of the mechanism underlying chronic inflammation in LC.

Link | PDF (Journal of Autoimmunity)

 

Canadian Consensus Criteria (team is Canadian).

 

Not sure I agree from the description they give.

"The second cohort consisted of 34 LC patients with ME/CFS (median age 48 ± 9.8, 25 females and 9 males) and 34 patients recovered (median age 45 ± 11.39, 24 females and 10 males) from SARS-CoV-2 infection without any long-term symptoms per se (Supplementary Table S2, Fig. 1A and B). Our ME/CFS patients were selected from a pool of over 2000 patients exhibiting LC symptoms. Through a comprehensive evaluation process that involved clinical assessments, laboratory tests, and the administration of well-defined questionnaires. Specifically, we utilized the de Paul Symptom Questionnaire (PSQ) to identify which patients fulfilled the criteria of ME/CFS; then used the FACIT Fatigue (Version 4) and multidimensional fatigue inventory to identify the severity of fatigue as outlined in the Canadian Consensus criteria (CDC) for ME/CFS and WHO [15,16] as we have previously described [17,18]. It is important to note that the majority of the >2000 LC patients did not present with ME/CFS, but rather exhibited other LC-related symptoms. We diligently selected those with ME/CFS from this cohort of LC patients."

 

"All participants were evaluated for the presence of criteria related to ME/CFS based on the DSQ; namely: fatigue (I), post-exertional malaise (II), sleep difficulties (III), pain (IV), neurological/cognitive manifestations (V), and other (VI) which included autonomic, neuroendocrine, and immune manifestations using a 5-point Likert scale ranging from 0: none of the time, 1: a little of the time, 2: about half the time, 3: most of the time, and 4: all of the time. The severity of the symptoms was also recorded using a 5-point Likert scale with 0: no symptom, 1: mild, 2: moderate, 3: severe, and 4: very severe. Each patient was considered positive if they scored a high frequency of symptoms over the past 6 months and severity (based on the impact of the symptom on their quality of life) of ≥2 in each of the 6 categories. For neurologic/cognitive manifestations, patients were considered positive if they scored a high frequency over the past 6 months and severity of ≥43 (out of a maximum score of 100) using the CFQ. For category VI (other symptoms), patients were considered positive if they had a minimum of one persistent symptom from two of the autonomic, neuroendocrine, and immune manifestations for at least 6 months. All of our LC patients in both cohorts met the criteria for categories I, II, III, IV, and/or V, and VI [[19], [20], [21]]. Those LC patients who did not meet these criteria were excluded from the study."

So ME/CFS was selected for using criteria based on the DSQ....

 

It's a comparison between people who are still inactive (PWME) and people that have returned to normal activity levels. They should follow up with a comparison between people who are inactive for non-ME reasons vs people who might have had the same cause but then returned to normal activity levels.

 

I wonder why anyone would want to publish in J Autoimmunity, which has been regarded as the dross of clinical immunology. It is not as if this is even an autoimmune disease, although they make passing mention of autoantibodies.

To get my interest up in reading a paper I need the abstract toggle some hard data and not tell readers what they are supposed to conclude from data that are not given.