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

Growth differentiation factor 15 (GDF-15) is a transforming growth factor (TGF)-beta 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.

Automated summary

Growth differentiation factor 15 (GDF-15) is a cytokine that plays a crucial role in regulating metabolism. It is produced in response to mitochondrial stress, tissue damage, or hypoxia, and is considered one of the strongest predictors of disease severity in inflammatory conditions, cancers, and infections. Although the exact mechanisms are still unclear, GDF-15 is believed to have tissue-protective effects through sympathetic and metabolic adaptation in the context of mitochondrial damage. This review discusses the emergence of GDF-15 as a distinct marker of viral infection severity, particularly in the context of COVID-19. It critically evaluates the role of GDF-15 as an inflammation-induced mediator of disease tolerance, involving metabolic and immune reprogramming. The review also explores potential mechanisms of GDF-15 elevation during COVID-19 cytokine storm and its limitations. Overall, GDF-15 appears to be involved in disease tolerance to viral infections, including SARS-CoV-2, and may serve as a target for novel therapeutic interventions.