Synolaki E, Papadopoulos V, Divolis G, et al. - The pathogenesis of several immuno-inflammatory disorders is reported to involve activins, which are members of the TGFβ-superfamily. In view of their previous works suggesting that over-expression of Activin-A in murine lung causes pathology sharing key features of COVID-19, researchers here examined the relevance, if any, of Activins and their natural inhibitor Follistatin in COVID-19 pathophysiology. They assessed 574 serum samples from 263 COVID-19 patients hospitalized in three independent centers for Activin-A, Activin-B and Follistatin levels, and compared these with common demographic, clinical and laboratory parameters. Findings revealed significant deregulation of the Activin/Follistatin-axis during the course of COVID-19, its correlation with severity and independent association with mortality. Overall a strong correlation was suggested between Activin/Follistatin-axis and COVID-19 mortality by this study along with introduction of FACT-CLINYCoD, a novel pathophysiology-based tool that aids in dynamic prediction of disease outcome, supporting clinical decision making.