New Publication: The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality

New Publication: The Activin/Follistatin-axis is severely deregulated in COVID-19 and independently associated with in-hospital mortality

J Infect Dis. 2021 Feb 24;jiab108. doi: 10.1093/infdis/jiab108. Online ahead of print.

E Synolaki, V Papadopoulos, G Divolis, O Tsahouridou, E Gavriilidis, G Loli, A Gavriil1, C Tsigalou, N Tziolos, E Sertaridou, B Kalra, A Kumar, P Rafailidis, A Pasternack, D Boumpas, G Germanidis, O Ritvos, S Metallidis, P Skendros, P Sideras

Background: Activins are members of the TGFβ-superfamily implicated in the pathogenesis of several immuno-inflammatory disorders. Based on our previous studies demonstrating that over-expression of Activin-A in murine lung causes pathology sharing key features of COVID-19, we hypothesized that Activins and their natural inhibitor Follistatin might be particularly relevant to COVID-19 pathophysiology.

Methods: Activin-A, Activin-B and Follistatin levels were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in three independent centers, and compared with common demographic, clinical and laboratory parameters. Optimal-scaling with ridge-regression was used to screen variables and establish a prediction model.

Result: The Activin/Follistatin-axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a novel disease scoring system, adding one point for each of Follistatin>6235pg/ml, Activin-A>591pg/ml, Activin-B>249pg/ml, CRP>10.3mg/dL, LDH>427U/L, Intensive Care Unit (ICU) admission, Neutrophil/Lymphocyte-Ratio>5.6, Age>61, Comorbidities>1 and D-dimers>1097ng/ml, efficiently predicted fatal outcome in an initial cohort (AUC: 0.951; 95%CI: 0.919-0.983, p<10 -6). Two independent cohorts that were used for validation indicated similar AUC values.

Conclusions: This study unravels strong link between Activin/Follistatin-axis and COVID-19 mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.

FULL TEXT in PDF format available at the publishers website: https://academic.oup.com/jid/advance-article/doi/10.1093/infdis/jiab108/6149149