@article{b5dfdb5c8917438489dc56a11c69fb97,
title = "Circulating osteopontin levels and outcomes in patients hospitalized for COVID-19",
abstract = "Background: Severe coronavirus disease 2019 (COVID-19) is the result of a hyper-inflam matory reaction to the severe acute respiratory syndrome coronavirus 2. The biomarkers of inflammation have been used to risk-stratify patients with COVID-19. Osteopontin (OPN) is an integrin-binding glyco-phosphoprotein involved in the modulation of leukocyte activation; its levels are associated with worse outcomes in patients with sepsis. Whether OPN levels predict outcomes in COVID-19 is unknown. Methods: We measured OPN levels in serum of 341 hospitalized COVID-19 patients collected within 48 h from admission. We characterized the determinants of OPN levels and examined their association with in-hospital outcomes; notably death, need for mechanical ventilation, and need for renal replacement therapy (RRT) and as a composite outcome. The risk discrimination ability of OPN was compared with other inflammatory biomarkers. Results: Patients with COVID-19 (mean age 60, 61.9% male, 27.0% blacks) had significantly higher levels of serum OPN compared to healthy volunteers (96.63 vs. 16.56 ng/mL, p < 0.001). Overall, 104 patients required mechanical ventilation, 35 needed dialysis, and 53 died during their hospitalization. In multivariable analyses, OPN levels ≥140.66 ng/mL (third tertile) were associated with a 3.5 × (95%CI 1.44–8.27) increase in the odds of death, and 4.9 × (95%CI 2.48–9.80) increase in the odds of requiring mechanical ventilation. There was no association between OPN and need for RRT. Finally, OPN levels in the upper tertile turned out as an independent prognostic factor of event-free survival with respect to the composite endpoint. Conclusion: Higher OPN levels are associated with increased odds of death and mechanical ventilation in patients with COVID-19, however, their utility in triage is questionable.",
keywords = "Coronavirus disease 2019, CRP, Death, Mechanical ventilation, OPN, Outcomes, PCT, Procalcitonin, Renal replacement therapy, Risk prediction, SARS-CoV-2",
author = "Hayek, {Salim S.} and Christoph Roderburg and Pennelope Blakely and Christopher Launius and Jesper Eugen-Olsen and Frank Tacke and Sofia Ktena and Verena Keitel and Mark Luedde and Giamarellos-Bourboulis, {Evangelos J.} and Tom Luedde and Loosen, {Sven H.}",
note = "Funding Information: Acknowledgments: Work in the lab of T.L. was funded from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation program through the ERC Consolidator Grant PhaseControl (Grant Agreement no 771083). The lab of T.L. was further supported by the German Cancer Aid (Deutsche Krebshilfe 110043 and a Mildred-Scheel-Professorship), the German-Research-Foundation (SFB-TRR57/P06, LU 1360/3-1, CRC1380/A01, and CA 830/3-1). SSH is funded by NHLBI 1R01HL153384-01, NIDDK U01-DK119083-03S1, MDiabetes, the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (U-M G024231) award. EJGB is supported by the Hellenic Institute for the Study of Sepsis and received funding from the Horizon2020 Marie-Curie Project European Sepsis Academy (granted to the National and Kapodistrian University of Athens), and the Horizon 2020 European Grants ImmunoSep and RISKinCOVID (granted to the Hellenic Institute for the Study of Sepsis). F.T. is supported through intramural funds from Charit{\'e} Universi-taetsmedizin Berlin and the Berlin Institute of Health. The authors acknowledge the University of Michigan Medical School Research Data Warehouse and DataDirect for providing data aggregation, management, and distribution services in support of the research reported in this publication. The authors are grateful to the services of the Microbiome Core supported by U2CDK110768, especially Chris Blair; the Michigan Clinical Research Unit including Wrenn Woodard and Dexter Hobdy, and the University of Michigan Medical School Central Biorepository for providing biospecimen storage, management, and distribution services in support of the research reported in the publication. Full list of ISIC Investigators: University of Michigan in Ann Arbor, USA: Salim S. Hayek, Pennelope Blakely, Christopher Launius, Hanna Berlin, Kingsley Amadi, Tariq U. Azam, Husam Shadid, Michael Pan, Patrick O{\textquoteright} Hayer, Chelsea Meloche, Rafey Feroze, Kishan J. Padalia, Elizabeth Anderson, Danny Perry, Abbas Bitar, Rayan Kaakati, Lili Zhao, Peiyao Zhao, Erinleigh Michaud, Yiyuan Huang, Toniemarie Catalan, Ibrahim Khaleel; Rush University in Chicago, USA: Jochen Reiser, Beata Samelko, Alexander Hlepas, Xuexiang Wang, Priya Patel; University of Copenhagen at Hvidovre Hospital, Denmark: Jesper Eugen-Olsen, Izzet Altintas, Jens Tingleff, Marius Stauning, Morten Baltzer Houlind, Mette B Lindstr{\o}m, Ove Andersen, Hejdi Gamst-Jensen, Line Jee Hartmann Rasmussen, Christian Rasmussen, Jan O Nehlin, Thomas Kallemose, Imran Parvaiz; Attikon University Hospital in Athens, Greece: Evangelos J. Giamarellos-Bourboulis, Maria-Evangelia Adami, Nicky Solomonidi, Maria Tsilika, Maria Saridaki, Vasileios Lekakis; University Hospital Dusseldorf, Germany: Sven Loosen, Tom Luedde, Verena Keitel; University of Thessaly, Greece: Athanasios Chalkias, Eleni Arnaoutoglou, Ioannis Pantazopoulos, Eleni Laou, Konstantina Kolonia, Anargyros Skoulakis; Charit{\'e} University Medicine Berlin, Germany: Frank Tacke, Pinkus Tober-Lau, Raphael Mohr, Florian Kurth, Leif Erik Sander, Christoph Jochum; University Hospital of Cologne, Germany: Philipp Koehler. Funding Information: Funding: The study is funded by the Frankel Cardiovascular Center COVID-19: Impact Research Ignitor (U-M G024231) award. Work in the lab of T.L. was funded from the European Research Council (ERC) under the European Union{\textquoteright}s Horizon 2020 research and innovation program through the ERC Consolidator Grant PhaseControl (Grant Agreement no 771083). The lab of T.L. was further supported by the German Cancer Aid (Deutsche Krebshilfe 110043 and a Mildred-Scheel-Professorship), the German-Research-Foundation (SFB-TRR57/P06, LU 1360/3-1, CRC1380/A01, and CA 830/3-1). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
doi = "10.3390/jcm10173907",
language = "English",
volume = "10",
journal = "Journal of Clinical Medicine",
issn = "2077-0383",
publisher = "M D P I AG",
number = "17",
}