Flower lose, a cell fitness marker, predicts COVID-19 prognosis

• Type of Material: Article
• Authors: Michail Yekelchyk, Max Planck Institute for Heart and Lung Research; Esha Madan, Champalimaud Centre for the Unknown; Jochen Wilhelm, Universities Giessen & Marburg Lung Center; Kirsty R. Short, University of Queensland; Antonio M. Palma, Champalimaud Centre for the Unknown; Linbu Liao, University of Copenhagen; Denise Camacho, Champalimaud Centre for the Unknown; Everlyne Nkadori, University of Wisconsin; Michael T. Winters, West Virginia University; Emily S. Rice, West Virginia University; Ines Rolim, Champalimaud Centre for the Unknown; Raquel Cruz-Duarte, University of Lisbon; Christopher Pelham, Eurofins Panlabs Inc.; Masaki Nagane, Azabu University; Kartik Gupta, University of Wisconsin; Sahil Chaudhary, University of Wisconsin; Thomas Braun, Max Planck Institute for Heart and Lung Research; Raghavendra Pillappa, Virginia Commonwealth University; Mark S. Parker, Virginia Commonwealth University; Thomas Menter, University Hospital Basel; Matthias Matter, University Hospital Basel; Jasmin Dionne Haslbauer, University Hospital Basel; Markus Tolnay, University Hospital Basel; Kornelia Galior, Emory University; Kristina A. Matkwoskyj, University of Wisconsin; Stephanie M. McGregor, University of Wisconsin; Laura K. Muller, University of Wisconsin; Emad A. Rakha, University of Nottingham; Antonio Lopez-Beltran, Champalimaud Centre for the Unknown; Ronny Drapkin, University of Pennsylvania; Maximilian Ackermann, Witten Herdecke University; Paul B. Fisher, Virginia Commonwealth University; Steven R. Grossman, Keck School of Medicine; Andrew K. Godwin, University of Kansas; Arutha Kulasinghe, University of Queensland; Ivan Martinez, West Virginia University; Clay B. Marsh, West Virginia University; Benjamin Tang, Nepean Hospital; Max S. Wicha, University of Michigan; Kyoung Jae Won, University of Copenhagen; Alexandar Tzankov, University Hospital Basel; Eduardo Moreno, Champalimaud Centre for the Unknown; Rajan Gogna, Champalimaud Centre for the Unknown
• Language: English
• Date: 2021-10-18
• Publisher: WILEY
• Publication Version: Final Published Version
• Copyright Statement: © 2021 The Authors.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.15252/emmm.202013714
• Title of Journal or Parent Work: EMBO MOLECULAR MEDICINE
• Volume: 13
• Issue: 11
• Start Page: e13714
• End Page: e13714
• Grant/Funding Information: This study was supported by Swiss Cancer League, Seeds of Science, UAMS, SNSF, Fundação para a Ciência e a Tecnologia, Fundamental Mandates (Stichting tegen Kanker—Fondation contre le Cancer) to R.G.; ERC, SNSF, Josef Steiner Cancer Research Foundation, Swiss Cancer League, and Champalimaud Foundation to E. Mo.; Novo Nordisk Foundation [NNF17CC0027852] and Lundbeck Foundation [R313–2019–421] to K.J.W.; La Caixa Funding LCF/BQ/PR20/11770006 to E. Ma.; FIS (Ministry of Health), Madrid, Spain, Grant PI17/01981 to A.L‐.B.;. DFG Clinical Research Unit KFO 309, and the German Center for Lung Research (DZL), DFG Collaborative Research Center SFB1021 to J.W.; Deutsche Forschungsgemeinschaft (DFG) Clinical Research Group KFO309 TP08, the DFG‐funded Excellence Cluster Cardio‐Pulmonary Institute (CPI), and the German Center for Lung Research (DZL) to T.B.; Botnar Research Centre for Child Health (BRCCH) (FTC‐2020‐10) and SNSF to A.T., T.M., M.M. & J.D.H.; Support from the Thelma Newmeyer Corman Chair in Cancer Research, the VCU Commercialization Fund and NIH/NCI R01 CA259599 to P.B.F.; Fundação para a Ciência e a Tecnologia Grant 2020.05319.BD to A.M.P.; Fundação para a Ciência e a Tecnologia Grant SFRH/BD/139138/2018 to R.C.D.; Fundação para a Ciência e a Tecnologia and PGCD—Programa de Pós‐Graduação Ciência para o Desenvolvimento Grant SFRH / BD/135367/2017 to D.C.; Tumor Microenvironment (TME) CoBRE Grant (NIH/NIGMS P20GM121322), West Virginia IDeA‐CTR (NIH/NIGMS 2U54 GM104942‐03), National Science Foundation (NSF/1920920, NSF/1761792), West Virginia IDeA Network of Biomedical Research Excellence (WV‐INBRE) (NIH/NIGMS P20GM103434) to I.M.; and Adelson Medical Research Foundation, NIH P50 SPORE CA228991, Honorable Tina Brozman Foundation for Ovarian Cancer Research to R.D. The author(s) thank the Translational Science Biocore (TSB) BioBank of the University of Wisconsin Carbone Cancer Center and the clinical laboratory at the University of Wisconsin Hospitals for providing specimens and associated clinical data used in this research. The Translational Science Biocore (TSB) BioBank of the University of Wisconsin Carbone Cancer Center and the clinical laboratory at the University of Wisconsin Hospitals are supported by P30 CA014520 and received dedicated support for COVID‐associated work from the University of Wisconsin School of Medicine and Public Health. We thank Taylor M. Parker for thorough reading of the manuscript. We thank Dr. Timothy Eubank at WVU for his kind support with the organization and purchase of RNA extraction kits (West Virginia Clinical and Translational Science Institute (WVCTSI) Grant GM104942).
• Keywords: prognosis; Science & Technology; biomarker; Research & Experimental Medicine; ELIMINATION; HEMATOPOIETIC STEM; OBESITY; COVID-19; Life Sciences & Biomedicine; cell fitness; Medicine, Research & Experimental; COMPETITION; flower
• Research Categories: Biology, Cell; Health Sciences, Public Health; Biology, Virology

Abstract

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e.g., death and hospitalization) in COVID-19 patients. We performed a post-mortem examination of infected lung tissue in deceased COVID-19 patients to determine hFwe-Lose’s biological role in acute lung injury. We then performed an observational study (n = 283) to evaluate whether hFwe-Lose expression (in nasopharyngeal samples) could accurately predict hospitalization or death in COVID-19 patients. In COVID-19 patients with acute lung injury, hFwe-Lose is highly expressed in the lower respiratory tract and is co-localized to areas of cell death. In patients presenting in the early phase of COVID-19 illness, hFwe-Lose expression accurately predicts subsequent hospitalization or death with positive predictive values of 87.8–100% and a negative predictive value of 64.1–93.2%. hFwe-Lose outperforms conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) 0.93–0.97 in predicting hospitalization/death. Specifically, this is significantly higher than the prognostic value of combining biomarkers (serum ferritin, D-dimer, C-reactive protein, and neutrophil–lymphocyte ratio), patient age and comorbidities (AUROC of 0.67–0.92). The cell fitness marker, hFwe-Lose, accurately predicts outcomes in COVID-19 patients. This finding demonstrates how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID-19 pandemic.