Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 223, Issue 9, Pages 1544-1554Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiab108
Keywords
COVID-19; SARS-CoV-2; activin; follistatin; outcome
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Funding
- Greek General Secretariat of Research and Technology [T1EDK-00617/CYTONET]
- European Infrastructure for Translational Medicine-Greece [OPS5028091]
- European Union (European Social Fund-ESF) through the Operational Programme <> [MIS-5000432]
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This study revealed a significant dysregulation of the activin/follistatin axis during the course of COVID-19, which correlated with disease severity and mortality. The introduced scoring system FACT-CLINYCoD efficiently predicted fatal outcomes of COVID-19 patients.
Background. Activins are members of the transforming growth factor-beta superfamily implicated in the pathogenesis of several immunoinflammatory disorders. Based on our previous studies demonstrating that overexpression of activin-A in murine lung causes pathology sharing key features of coronavirus disease 2019 (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 were retrospectively analyzed in 574 serum samples from 263 COVID-19 patients hospitalized in 3 independent centers, and compared with demographic, clinical, and laboratory parameters. Optimal scaling with ridge regression was used to screen variables and establish a prediction model. Result. Me activin/follistatin axis was significantly deregulated during the course of COVID-19, correlated with severity and independently associated with mortality. FACT-CLINYCoD, a scoring system incorporating follistatin, activin-A, activin-B, C-reactive protein, lactate dehydrogenase, intensive care unit admission, neutrophil/lymphocyte ratio, age, comorbidities, and D-dimers, efficiently predicted fatal outcome (area under the curve [AUC], 0.951; 95% confidence interval, .919-.983; P <10(-6)). Two validation cohorts indicated similar AUC values. Conclusions. This study demonstrates a 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.
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