Coping With Stress: The Mitokine GDF-15 as a Biomarker of COVID-19 Severity

Abstract

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-β superfamily cytokine that plays a central role in metabolism regulation. Produced in response to mitochondrial stress, tissue damage or hypoxia, this cytokine has emerged as one of the strongest predictors of disease severity during inflammatory conditions, cancers and infections. Reports suggest that GDF-15 plays a tissue protective role via sympathetic and metabolic adaptation in the context of mitochondrial damage, although the exact mechanisms involved remain uncertain. In this review, we discuss the emergence of GDF-15 as a distinctive marker of viral infection severity, especially in the context of COVID-19. We will critically review the role of GDF-15 as an inflammation-induced mediator of disease tolerance, through metabolic and immune reprogramming. Finally, we discuss potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Altogether, this cytokine seems to be involved in disease tolerance to viral infections including SARS-CoV-2, paving the way for novel therapeutic interventions.

Markers of fungal translocation are elevated during post-acute sequelae of SARS-CoV-2 and induce NF-κB signaling

“…Analyzing the impact of the potential fungal translocation during PASC on immune cell activation (such as the coexpression of CD38 and HLA-DR on T cells), other markers of systemic inflammation and immune dysfunction during COVID-19 (such as GDF-15 and galectins, refs. 55 , 141 ), and the expression of β-glucan receptors (such as Dectin-1 on monocytes and NKp30 on NK cells), in the intestines and systemically, will be also needed in future studies. Finally, correcting for additional potential confounders will require validating our results in larger independent cohorts from varying geographic settings and demographic groups.…”

GDF15 and ACE2 stratify COVID-19 patients according to severity while ACE2 mutations increase infection susceptibility

“…Unfortunately, we did not find differences in circulating mtDNA in our population, although COVID-19 patients presented higher levels compared to the uninfected control patients. GDF15 is upregulated in situations of hypoxia and tissue damage (Ahmed et al, 2022). However, knowledge of its pathophysiological function at the molecular level is still limited and more studies are needed.…”

GDF15 and ACE2 stratify COVID19 patients according to severity while ACE2 mutations increase infection susceptibility

“…GDF15 is upregulated in situations of hypoxia and tissue damage (44). However, knowledge of its pathophysiological function at the molecular level is still limited and more studies are needed.…”

“…GDF15 is a known marker of mitochondrial dysfunction, and due to its function as hormone-cytokine may play an important role in the regulation of cellular oxygenation and the inflammatory response, all of which are key mechanisms in the pathophysiology of COVID-19. GDF15 is upregulated in situations of hypoxia and tissue damage (44). However, knowledge of its pathophysiological function at the molecular level is still limited and more studies are needed.…”