The Activin/Follistatin Axis Is Severely Deregulated in COVID-19 and Independently Associated With In-Hospital Mortality

Abstract Background Activins are members of the transforming growth factor-? superfamily implicated in pathogenesis several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression activin-A murine lung causes pathology sharing key features coronavirus disease 2019 (COVID-19), we hypothesized activins and their natural inhibitor follistatin might be particularly relevant to COVID-19 pathophysiology. Methods Activin-A, activin-B, were retrospectively analyzed 574 serum samples from 263 patients hospitalized 3 independent centers, compared with demographic, clinical, laboratory parameters. Optimal scaling ridge regression was used screen variables establish a prediction model. Result The activin/follistatin axis significantly deregulated during course COVID-19, correlated severity independently associated mortality. FACT-CLINYCoD, scoring system incorporating follistatin, activin-A, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, D-dimers, efficiently predicted fatal outcome (area under curve [AUC], 0.951; 95% confidence interval, .919?.983; P <10?6). Two validation cohorts indicated similar AUC values. Conclusions This study demonstrates link between mortality introduces novel pathophysiology-based tool allows dynamic outcome, supporting clinical decision making.