Exploring the role of galectin-9 and artemin as biomarkers in long COVID with chronic fatigue syndrome: links to inflammation and cognitive function

Front Immunol. 2024 Sep 25:15:1443363. doi: 10.3389/fimmu.2024.1443363. eCollection 2024.

Abstract

This study aimed to assess plasma galectin-9 (Gal-9) and artemin (ARTN) concentrations as potential biomarkers to differentiate individuals with Long COVID (LC) patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) from SARS-CoV-2 recovered (R) and healthy controls (HCs). Receiver operating characteristic (ROC) curve analysis determined a cut-off value of plasma Gal-9 and ARTN to differentiate LC patients from the R group and HCs in two independent cohorts. Positive correlations were observed between elevated plasma Gal-9 levels and inflammatory markers (e.g. SAA and IP-10), as well as sCD14 and I-FABP in LC patients. Gal-9 also exhibited a positive correlation with cognitive failure scores, suggesting its potential role in cognitive impairment in LC patients with ME/CFS. This study highlights plasma Gal-9 and/or ARTN as sensitive screening biomarkers for discriminating LC patients from controls. Notably, the elevation of LPS-binding protein in LC patients, as has been observed in HIV infected individuals, suggests microbial translocation. However, despite elevated Gal-9, we found a significant decline in ARTN levels in the plasma of people living with HIV (PLWH). Our study provides a novel and important role for Gal-9/ARTN in LC pathogenesis.

Keywords: HIV; artemin; chronic fatigue syndrome; galectin-9; long COVID; microbial translocation.

MeSH terms

  • Adult
  • Antigens, Neoplasm
  • Biomarkers* / blood
  • Biomarkers, Tumor
  • COVID-19* / blood
  • COVID-19* / complications
  • COVID-19* / diagnosis
  • COVID-19* / immunology
  • Cognition
  • Fatigue Syndrome, Chronic* / blood
  • Fatigue Syndrome, Chronic* / diagnosis
  • Fatigue Syndrome, Chronic* / etiology
  • Female
  • Galectins* / blood
  • Humans
  • Inflammation* / blood
  • Male
  • Middle Aged
  • Nerve Tissue Proteins* / blood
  • SARS-CoV-2*

Substances

  • Galectins
  • Biomarkers
  • LGALS9 protein, human
  • Nerve Tissue Proteins
  • LGALS3BP protein, human
  • Antigens, Neoplasm
  • Biomarkers, Tumor

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was primarily supported by a grant from the Canadian Institutes of Health Research (CIHR #174901) to SE. SS is supported by a CIHR REDI Early Career Transition Award. This study was in part supported by an innovation grant from the Li Ka Shing Institute of virology to MO and SE.