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

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

Shokrollah Elahi  1   2   3   4   5   6 , Maryam Rezaeifar  1 , Mohammed Osman  2   3   7 , Shima Shahbaz  1
Affiliations

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

Shokrollah Elahi et al. Front Immunol. .

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.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision.

Figures

Figure 1
Figure 1
The diagnostic value of galectin-9 (Gal-9) in Long-COVID patients. (A) The receiver operating characteristic (ROC) curve for Gal-9 in LC versus healthy controls (HC) in the discovery cohort. (B) The ROC curve for Gal-9 in LC versus recovered individuals (R) in the discovery cohort. (C) The ROC curve for Gal-9 in LC versus R in the validating cohort. (D) The correlation between plasma Gal-9 and SAA, and (E) IP-10 levels in LC patients of the discovery cohort. (F) The correlation between plasma Gal-9 and SAA, and (G) IP-10 levels in LC patients of the validating cohort.
Figure 2
Figure 2
The correlation of Gal-9 with inflammatory and cognitive impairment in LC patients. (A) The correlation between plasma sCD14 and Gal-9 in the discovery, and (B) validating cohort. (C) The correlation between plasma I-FABP and Gal-9 in the discovery, and (D) validating cohort. (E) Detected concentrations of LPS-binding protein (LPS-BP) in the plasma of LC versus R in both cohorts. (F) The correlation between plasma Gal-9 and cognitive failure score in the discovery, and (G) validating cohort. The symbol **** shows a p value less than 0.0001 or P < 0.0001.
Figure 3
Figure 3
The diagnostic value of artemin (ARTN) in Long-COVID patients. (A) The ROC curve for ARTN in LC versus HCs in the discovery cohort. (B) The ROC curve for ARTN in LC versus the R group in the discovery cohort. (C) The ROC curve for ARTN in LC versus R in the validating cohort. (D) The correlation between plasma Gal-9 and ARTN in LC patients of the discovery, and (E) validating cohort. (F) Detected ARTN levels in plasma samples from HIV-infected individuals, HCs and LC patients of both cohorts. (G) TGF-β levels in plasma samples from HIV-infected individual versus HCs. The symbol **** shows a p value less than 0.0001 or P < 0.0001.
Figure 4
Figure 4
The proposed graphic summary. The gastrointestinal involvement during acute SARS-CoV-2 infection and the possible persistence of viral antigen/replication beyond the acute phase result in compromised gut barrier integrity. This, subsequently, leads to the translocation of microbial by-products (e.g. LPS) into the blood circulation. This leads to the activation of innate immune cells and the release of variety of pro-inflammatory cytokines and chemokines. This inflammatory cascade may result in immune/non-immune cell apoptosis and the release of damage-associated molecular patterns (e.g. Gal-9). Gal-9 may influence the activation/deactivation of different immune cells and ultimately may directly/indirectly influence the effector functions of microglia and astrocytes.
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References

    1. Davis HE, McCorkell L, Vogel JM, Topol EJ. Long COVID: major findings, mechanisms and recommendations. Nat Rev Microbiol. (2023) 21:133–46. doi: 10.1038/s41579-022-00846-2 - DOI - PMC - PubMed
    1. Glynne P, Tahmasebi N, Gant V, Gupta R. Long COVID following mild SARS-CoV-2 infection: characteristic T cell alterations and response to antihistamines. J Investig Med. (2022) 70:61–7. doi: 10.1136/jim-2021-002051 - DOI - PMC - PubMed
    1. Gorna R, MacDermott N, Rayner C, O'Hara M, Evans S, Agyen L, et al. . Long COVID guidelines need to reflect lived experience. Lancet. (2021) 397:455–7. doi: 10.1016/S0140-6736(20)32705-7 - DOI - PMC - PubMed
    1. Saito S, Shahbaz S, Luo X, Osman M, Redmond D, Cohen Tervaert JW, et al. . Metabolomic and immune alterations in long COVID patients with chronic fatigue syndrome. Front Immunol. (2024) 15:1341843. doi: 10.3389/fimmu.2024.1341843 - DOI - PMC - PubMed
    1. Bai F, Tomasoni D, Falcinella C, Barbanotti D, Castoldi R, Mulè G, et al. . Female gender is associated with long COVID syndrome: a prospective cohort study. Clin Microbiol Infect. (2022) 28:611.e9–611.e16. doi: 10.1016/j.cmi.2021.11.002 - DOI - PMC - PubMed

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.