Mortality Risk and Urinary Proteome Changes in Acute COVID-19 Survivors in the Multinational CRIT-COV-U Study.
Justyna Siwy, Felix Keller, Mirosław Banasik, Björn Peters, Emmanuel Dudoignon, Alexandre Mebazaa, Dilara Gülmez, Goce Spasovski, Mercedes Salgueira Lazo, Marek W Rajzer, Łukasz Fuławka, Magdalena Dzitkowska-Zabielska, Harald Mischak, Manfred Hecking, Joachim Beige, Ralph Wendt
Felix Keller: Department of Internal Medicine IV (Nephrology and Hypertension), Medical University of Innsbruck, 6020 Innsbruck, Austria. ORCID
Mirosław Banasik: Department of Nephrology and Transplantation Medicine, Wrocław Medical University, 50-556 Wroclaw, Poland. ORCID
Björn Peters: Department of Molecular and Clinical Medicine, Institute of Medicine, The Sahlgrenska Academy at University of Gothenburg, 413 45 Gothenburg, Sweden.
Emmanuel Dudoignon: Department of Anaesthesiology and Critical Care, Saint Louis-Hôpital Lariboisière, AP-HP, 75010 Paris, France.
Alexandre Mebazaa: Department of Anaesthesiology and Critical Care, Saint Louis-Hôpital Lariboisière, AP-HP, 75010 Paris, France.
Dilara Gülmez: Department of Epidemiology, Medical University of Vienna, 1090 Vienna, Austria. ORCID
Goce Spasovski: Department of Nephrology, University Sts. Cyril and Methodius, 1000 Skopje, North Macedonia.
Mercedes Salgueira Lazo: Virgen Macarena Hospital, University of Seville, 41009 Seville, Spain.
Marek W Rajzer: First Department of Cardiology, Interventional Electrocardiology and Arterial Hypertension, Jagiellonian University Medical College, 30-688 Kraków, Poland.
Łukasz Fuławka: Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wrocław, Poland. ORCID
Magdalena Dzitkowska-Zabielska: Faculty of Physical Education, Gdańsk University of Physical Education and Sport, 80-336 Gdańsk, Poland. ORCID
Harald Mischak: Mosaiques Diagnostics GmbH, 30659 Hannover, Germany. ORCID
Manfred Hecking: Department of Epidemiology, Medical University of Vienna, 1090 Vienna, Austria. ORCID
Joachim Beige: Kuratorium for Dialysis and Transplantation (KfH) Leipzig, 04129 Leipzig, Germany.
Ralph Wendt: Department of Nephrology, St. Georg Hospital Leipzig, 04129 Leipzig, Germany. ORCID
BACKGROUND/OBJECTIVES: Survival prospects following SARS-CoV-2 infection may extend beyond the acute phase, influenced by various factors including age, health conditions, and infection severity; however, this topic has not been studied in detail. Therefore, within this study, the mortality risk post-acute COVID-19 in the CRIT-COV-U cohort was investigated. METHODS: Survival data from 651 patients that survived an acute phase of COVID-19 were retrieved and the association between urinary peptides and future death was assessed. Data spanning until December 2023 were collected from six countries, comparing mortality trends with age- and sex-matched COVID-19-negative controls. A death prediction classifier was developed and validated using pre-existing urinary peptidomic datasets. RESULTS: Notably, 13.98% of post-COVID-19 patients succumbed during the follow-up, with mortality rates significantly higher than COVID-19-negative controls, particularly evident in younger individuals (<65 years). These data for the first time demonstrate that SARS-CoV-2 infection highly significantly increases the risk of mortality not only during the acute phase of the disease but also beyond for a period of about one year. In our study, we were further able to identify 201 urinary peptides linked to mortality. These peptides are fragments of albumin, alpha-2-HS-glycoprotein, apolipoprotein A-I, beta-2-microglobulin, CD99 antigen, various collagens, fibrinogen alpha, polymeric immunoglobulin receptor, sodium/potassium-transporting ATPase, and uromodulin and were integrated these into a predictive classifier (DP201). Higher DP201 scores, alongside age and BMI, significantly predicted death. CONCLUSIONS: The peptide-based classifier demonstrated significant predictive value for mortality in post-acute COVID-19 patients, highlighting the utility of urinary peptides in prognosticating post-acute COVID-19 mortality, offering insights for targeted interventions. By utilizing these defined biomarkers in the clinic, risk stratification, monitoring, and personalized interventions can be significantly improved. Our data also suggest that mortality should be considered as one possible symptom or a consequence of post-acute sequelae of SARS-CoV-2 infection, a fact that is currently overlooked.
