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This collaborative study by 15 institutions across Europe aimed to develop a machine learning model for predicting the risk of in-hospital mortality post-SARS-CoV-2 infection. Blood samples and clinical data from 1286 COVID-19 patients collected from 2020 to 2023 across four cohorts in Europe and Canada were analyzed, with 2906 long non-coding RNAs profiled using targeted sequencing. From a discovery cohort combining three European cohorts and 804 patients, age and the long non-coding RNA LEF1-AS1 were identified as predictive features, yielding an AUC of 0.83 (95% CI 0.82\u20130.84) and a balanced accuracy of 0.78 (95% CI 0.77\u20130.79) with a feedforward neural network classifier. Validation in an independent Canadian cohort of 482 patients showed consistent performance. Cox regression analysis indicated that higher levels of LEF1-AS1 correlated with reduced mortality risk (age-adjusted hazard ratio 0.54, 95% CI 0.40\u20130.74). 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P.F. is the founder and CEO of Pharmahungary Group, a group of R&D companies. J.J.V. has personal fees from Merck \/ MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Center for Infection Research (DZIF), University Hospital Freiburg\/ Congress and Communication, Academy for Infectious Medicine, University Manchester, German Society for Infectious Diseases (DGI), \u00c4rztekammer Nordrhein, University Hospital Aachen, Back Bay Strategies, German Society for Internal Medicine (DGIM), Shionogi, Molecular Health, Netzwerk Universit\u00e4tsmedizin, Janssen, NordForsk, Biontech, APOGEPHA. J.J.V. has grants from Merck \/ MSD, Gilead, Pfizer, Astellas Pharma, Basilea, German Center for Infection Research (DZIF), German Federal Ministry of Education and Research (BMBF), Deutsches Zetrum f\u00fcr Luft- und Raumfahrt (DLR), University of Bristol, Rigshospitalet Copenhagen, Network University Medicine. L.B. declares to have acted as a SAB member of Sanofi, Ionnis, MSD and NovoNordisk; to have received speaker fees from Sanofi, Bayer and AB-Biotics SA and to have founded the spin-off Ivastatin Therapeutics S.L. (all unrelated to this work). T.P. declares to have received speaker fees from AB-Biotics SA, and to be a co-founder of the Spin-off Ivastatin Therapeutics S.L. (all unrelated to this work). M.S. received funding from Pfizer Inc. and from Owkin for projects not related to this research. N.L.M. has received honoraria from Abbott Diagnostics, Siemens Healthineers, Roche Diagnostics and LumiraDx. The University of Edinburgh has received research grants from Abbott Diagnostics, Novo Nordisk, and Siemens Healthineers. H.F. is the founder and owner of Firalis SA, a company commercializing the FIMICS panel. He holds patents and licenses for the use of RNAs as biomarkers and therapeutic targets. 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