Jan A Staessen, Ralph Wendt, Yu-Ling Yu, Sven Kalbitz, Lutgarde Thijs, Justyna Siwy, Julia Raad, Jochen Metzger, Barbara Neuhaus, Armin Papkalla, Heiko von der Leyen, Alexandre Mebazaa, Emmanuel Dudoignon, Goce Spasovski, Mimoza Milenkova, Aleksandra Canevska-Taneska, Mercedes Salgueira Lazo, Mina Psichogiou, Marek W Rajzer, Łukasz Fuławka, Magdalena Dzitkowska-Zabielska, Guenter Weiss, Torsten Feldt, Miriam Stegemann, Johan Normark, Alexander Zoufaly, Stefan Schmiedel, Michael Seilmaier, Benedikt Rumpf, Mirosław Banasik, Magdalena Krajewska, Lorenzo Catanese, Harald D Rupprecht, Beata Czerwieńska, Björn Peters, Åsa Nilsson, Katja Rothfuss, Christoph Lübbert, Harald Mischak, Joachim Beige, Lukasz Fulawka, Harald Rupprecht, Beata Czerwienska, Jörg Ermisch, Nils Kellner, Lydia Peruth-Stutzmann, Stefanie Schroth, Jonathan Schmidt, Ulrike Schmidt, Daniel Breuer, Fariza Abeud, Marie-Celine Fournier, Badr Louadah, Rocio Molas, Fraile Loreto Rojas, Fabiola Alonso García, Isabel Garcia Sánchez, Ioana Cezara Hrom, Andrzej Więczek., Matthias Schwab, Kei K Asayama, Tine W Hansen, Gladys E Maestre, Dimitrios Basoulis, Georgios Karamanakos., Pawel Lis, Agnieszka Olszanecka, Rosa Bellmann-Weiler, Lucas Lanser, Alicia Edin, Matthias NE Forsell, Bernd Stegmayr, Björn-Erik Ole Jensen, Hans-Martin Orth, Sylke Borstel, Agata Mikolajewska, Manfred Hecking, Lukas Schmölz, Michał Hoffmann, Krzysztof Narkiewicz, Agnieszka Matera-Witkiewicz, Justyna Zachciał, Monika Litwin, and Patrycja Marciniak
BACKGROUND: The SARS-CoV-2 pandemic is a worldwide challenge. The CRIT-CoV-U pilot study generated a urinary proteomic biomarker consisting of 50 peptides (COV50), which predicted death and disease progression from SARS-CoV-2. After the interim analysis presented for the German Government, here, we aimed to analyse the full dataset to consolidate the findings and propose potential clinical applications of this biomarker. METHODS: CRIT-CoV-U was a prospective multicentre cohort study. In eight European countries (Austria, France, Germany, Greece, North Macedonia, Poland, Spain, and Sweden), 1012 adults with PCR-confirmed COVID-19 were followed up for death and progression along the 8-point WHO scale. Capillary electrophoresis coupled with mass spectrometry was used for urinary proteomic profiling. Statistical methods included logistic regression and receiver operating characteristic curve analysis with a comparison of the area under curve (AUC) between nested models. Hospitalisation costs were derived from the care facility corresponding with the Markov chain probability of reaching WHO scores ranging from 3 to 8 and flat-rate hospitalisation costs adjusted for the gross per capita domestic product of each country. FINDINGS: From June 30 to Nov 19, 2020, 228 participants were recruited, and from April 30, 2020, to April 14, 2021, 784 participants were recruited, resulting in a total of 1012 participants. The entry WHO scores were 1-3 in 445 (44%) participants, 4-5 in 529 (52%) participants, and 6 in 38 (4%) participants; and of all participants, 119 died and 271 had disease progression. The odds ratio (OR) associated with COV50 in all 1012 participants for death was 2·44 (95% CI 2·05-2·92) unadjusted and 1·67 (1·34-2·07) when adjusted for sex, age, BMI, comorbidities, and baseline WHO score; and for disease progression, the OR was 1·79 (1·60-2·01) when unadjusted and 1·63 (1·41-1·91) when adjusted (p