Evgenia Synolaki1, Vasileios Papadopoulos2, Georgios Divolis1, Olga Tsahouridou3, Efstratios Gavriilidis2, Georgia Loli3, Ariana Gavriil1, Christina Tsigalou4, Nikolaos R Tziolos5, Eleni Sertaridou6, Bhanu Kalra7, Ajay Kumar7, Petros Rafailidis8, Arja Pasternack9, Dimitrios T Boumpas5, Georgios Germanidis3, Olli Ritvos9, Simeon Metallidis3, Panagiotis Skendros2,10, Paschalis Sideras1. 1. Biomedical Research Foundation Academy of Athens, Center for Clinical, Experimental Surgery and Translational Research, Athens, Greece. 2. First Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. 3. First Department of Internal Medicine, AHEPA University Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece. 4. Laboratory of Microbiology, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. 5. Fourth Department of Internal Medicine, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece. 6. Intensive Care Unit, University Hospital of Alexandroupolis, Alexandroupolis, Greece. 7. Ansh Labs, Webster, Texas, USA. 8. Second Department of Internal Medicine, University Hospital of Alexandroupolis, Democritus University of Thrace, Alexandroupolis, Greece. 9. Department of Physiology, Faculty of Medicine, University of Helsinki, Helsinki, Finland. 10. Laboratory of Molecular Hematology, Democritus University of Thrace, Alexandroupolis, Greece.
Abstract
BACKGROUND: Activins are members of the transforming growth factor-β 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: The 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.
BACKGROUND: Activins are members of the transforming growth factor-β 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-19patients 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: The 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-19mortality and introduces FACT-CLINYCoD, a novel pathophysiology-based tool that allows dynamic prediction of disease outcome, supporting clinical decision making.
Authors: Samuel Kou; Sammi Kile; Sai Samhith Kambampati; Evelyn C Brady; Hayley Wallace; Carlos M De Sousa; Kin Cheung; Lauren Dickey; Kelly L Wentworth; Edward Hsiao Journal: Res Sq Date: 2021-09-16
Authors: Samuel Kou; Sammi Kile; Sai Samhith Kambampati; Evelyn C Brady; Hayley Wallace; Carlos M De Sousa; Kin Cheung; Lauren Dickey; Kelly L Wentworth; Edward C Hsiao Journal: Orphanet J Rare Dis Date: 2022-03-04 Impact factor: 4.123
Authors: Megan McAleavy; Qian Zhang; Peter J Ehmann; Jianing Xu; Matthew F Wipperman; Dharani Ajithdoss; Li Pan; Matthew Wakai; Raphael Simonson; Abhilash Gadi; Adelekan Oyejide; Sara C Hamon; Anita Boyapati; Lori G Morton; Tea Shavlakadze; Christos A Kyratsous; David J Glass Journal: Mol Cell Biol Date: 2021-11-01 Impact factor: 4.272