GDF15: an emerging modulator of immunity and a strategy in COVID-19 in association with iron metabolism

Rochette, Luc; Zeller, Marianne; Cottin, Yves; Vergely, Catherine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of respiratory and cardiovascular diseases, known as coronavirus disease 2019 (COVID-19). SARS-CoV-2 encodes structural proteins spike (S), E, M and N. The receptor-binding domain on the surface subunit S1 is responsible for attachment of the virus to angiotensin-converting enzyme 2 (ACE2). ACE2 is highly expressed in host cells. The cytokine storm observed in COVID-19 patients contributes to the endothelial vascular dysfunction, which can lead to acute respiratory distress syndrome, multiorgan failure, alteration in iron homeostasis, and death. Growth and differentiation factor 15 (GDF15), which belongs to the transforming growth factor-β (TGF-β) superfamily of proteins, plays a pivotal role in the development and progression of diseases because of its role as a metabolic regulator. In COVID-19, GDF15 activity increases in response to tissue damage. GDF15 appears to be a strong predictor of poor outcomes in critically COVID-19 patients and acts as an “inflammation-induced central mediator of tissue tolerance” via its metabolic properties. In this review, we will examine the potential properties of GDF15 as an emerging modulator of immunity in COVID-19 in association with iron metabolism. The virus life cycle in host cell provides potential targets for drug therapy.