Machine Learning Based Prediction of COVID-19 Mortality Suggests Repositioning of Anticancer Drug for Treating Severe Cases
Machine Learning Based Prediction of COVID-19 Mortality Suggests Repositioning of Anticancer Drug for Treating Severe Cases
Abstract Despite available vaccinations COVID-19 case numbers around the world are still growing, and effective medications against severe cases are lacking. In this work, we developed a machine learning model which predicts mortality for COVID-19 patients using data from the multi-center ‘Lean European Open Survey on SARS-CoV-2-infected patients’ (LEOSS) observational study (>100 active sites in Europe, primarily in Germany), resulting into an AUC of almost 80%. We showed that molecular mechanisms related to dementia, one of the relevant predictors in our model, intersect with those associated to COVID-19. Most notably, among these molecules was tyrosine kinase 2 (TYK2), a protein that has been patented as drug target in Alzheimer’s Disease but also genetically associated with severe COVID-19 outcomes. We experimentally verified that anti-cancer drugs Sorafenib and Regorafenib showed a clear anti-cytopathic effect in Caco2 and VERO-E6 cells and can thus be regarded as potential treatments against COVID-19. Altogether, our work demonstrates that interpretation of machine learning based risk models can point towards drug targets and new treatment options, which are strongly needed for COVID-19.
Fr?hlich Holger、LEOSS study group、Hanses Frank、Domingo-Fern¨￠ndez Daniel、Kodamullil Alpha Tom、Schneider Jochen、Ruethrich Maria Madeleine、Feldt Thorsten、Wyen Christoph、Roemmele Christoph、Stecher Melanie、DeLong Lauren Nicole、Hertenstein Bernd、Vehreschild J?rg Janne、Borgmann Stefan、Kuzikov Maria、Zaliani Andrea、Hower Martin、Jakob Carolin E. M.、Vehreschild Maria J.G.T.、Wille Kai、Linden Thomas、Lanznaster Julia、Rieg Siegbert
Fraunhofer Institute for Algorithms and Scientific Computing (SCAI)||University of Bonn, Bonn-Aachen International Center for ITEmergency Department, University Hospital Regensburg||Department for Infectious Diseases and Infection Control, University Hospital RegensburgFraunhofer Institute for Algorithms and Scientific Computing (SCAI)Fraunhofer Institute for Algorithms and Scientific Computing (SCAI)Clinic and Polyclinic for Internal Medicine II, Technical University of MunichInstitute for Infection Medicine and Hospital Hygiene, University Hospital JenaDepartment of Gastroenterology, Hepatology and Infectious Diseases, University Hospital D¨1sseldorf, Medical Faculty of Heinrich Heine University D¨1sseldorfChristoph Wyen, Praxis am Ebertplatz CologneInternal Medicine III - Gastroenterology and Infectious Diseases, University Hospital AugsburgDepartment I for Internal Medicine, University Hospital of Cologne, University of CologneFraunhofer Institute for Algorithms and Scientific Computing (SCAI)||University of Bonn, Bonn-Aachen International Center for ITDepartment of Medicine II, University Hospital FreiburgDepartment II of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe UniversityDepartment of Infectious Diseases and Infection Control, Hospital IngolstadtFraunhofer Institute for Translational Medicine and Pharmacologie (ITMP), VolksparkLabsFraunhofer Institute for Translational Medicine and Pharmacologie (ITMP), VolksparkLabsDepartment of Pneumology, Infectious Diseases and Intensive Care, Klinikum Dortmund gGmbH, Hospital of University Witten / HerdeckeDepartment I for Internal Medicine, University Hospital of Cologne, University of CologneDepartment II of Internal Medicine, Infectious Diseases, University Hospital Frankfurt, Goethe UniversityUniversity Clinic for Haematology, Oncology, Haemostaseology and Palliative Care, Johannes Wesling Medical Centre MindenFraunhofer Institute for Algorithms and Scientific Computing (SCAI)||University of Bonn, Bonn-Aachen International Center for ITDepartment of Internal Medicine II, Hospital PassauDepartment of Medicine II, University Hospital Freiburg
医学研究方法基础医学药学
precision medicinecovid19machine learningdrug repositioningexplainable ai
Fr?hlich Holger,LEOSS study group,Hanses Frank,Domingo-Fern¨￠ndez Daniel,Kodamullil Alpha Tom,Schneider Jochen,Ruethrich Maria Madeleine,Feldt Thorsten,Wyen Christoph,Roemmele Christoph,Stecher Melanie,DeLong Lauren Nicole,Hertenstein Bernd,Vehreschild J?rg Janne,Borgmann Stefan,Kuzikov Maria,Zaliani Andrea,Hower Martin,Jakob Carolin E. M.,Vehreschild Maria J.G.T.,Wille Kai,Linden Thomas,Lanznaster Julia,Rieg Siegbert.Machine Learning Based Prediction of COVID-19 Mortality Suggests Repositioning of Anticancer Drug for Treating Severe Cases[EB/OL].(2025-03-28)[2025-05-28].https://www.medrxiv.org/content/10.1101/2021.11.11.21266048.点此复制
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