EMBO Molecular Medicine (Oct 2021)
Flower lose, a cell fitness marker, predicts COVID‐19 prognosis
- Michail Yekelchyk,
- Esha Madan,
- Jochen Wilhelm,
- Kirsty R Short,
- António M Palma,
- Linbu Liao,
- Denise Camacho,
- Everlyne Nkadori,
- Michael T Winters,
- Emily S Rice,
- Inês Rolim,
- Raquel Cruz‐Duarte,
- Christopher J Pelham,
- Masaki Nagane,
- Kartik Gupta,
- Sahil Chaudhary,
- Thomas Braun,
- Raghavendra Pillappa,
- Mark S Parker,
- Thomas Menter,
- Matthias Matter,
- Jasmin Dionne Haslbauer,
- Markus Tolnay,
- Kornelia D Galior,
- Kristina A Matkwoskyj,
- Stephanie M McGregor,
- Laura K Muller,
- Emad A Rakha,
- Antonio Lopez‐Beltran,
- Ronny Drapkin,
- Maximilian Ackermann,
- Paul B Fisher,
- Steven R Grossman,
- Andrew K Godwin,
- Arutha Kulasinghe,
- Ivan Martinez,
- Clay B Marsh,
- Benjamin Tang,
- Max S Wicha,
- Kyoung Jae Won,
- Alexandar Tzankov,
- Eduardo Moreno,
- Rajan Gogna
Affiliations
- Michail Yekelchyk
- Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research
- Esha Madan
- Champalimaud Centre for the Unknown
- Jochen Wilhelm
- Universities Giessen & Marburg Lung Center, German Center for Lung Research (DZL), Justus‐Liebig‐University
- Kirsty R Short
- School of Chemistry and Molecular Biosciences, The University of Queensland
- António M Palma
- Champalimaud Centre for the Unknown
- Linbu Liao
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen
- Denise Camacho
- Champalimaud Centre for the Unknown
- Everlyne Nkadori
- Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin‐Madison School of Medicine and Public Health
- Michael T Winters
- Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University
- Emily S Rice
- Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University
- Inês Rolim
- Champalimaud Centre for the Unknown
- Raquel Cruz‐Duarte
- Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa
- Christopher J Pelham
- Eurofins Panlabs Inc.
- Masaki Nagane
- Department of Biochemistry, School of Veterinary Medicine, Azabu University
- Kartik Gupta
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin
- Sahil Chaudhary
- Department of Surgery, School of Medicine and Public Health, University of Wisconsin
- Thomas Braun
- Department of Cardiac Development and Remodelling, Max Planck Institute for Heart and Lung Research
- Raghavendra Pillappa
- Department of Pathology, Virginia Commonwealth University School of Medicine
- Mark S Parker
- Department of Diagnostic Radiology and Internal Medicine, Early Detection Lung Cancer Screening Program, Thoracic Imaging Division, Thoracic Imaging Fellowship Program, VCU Health Systems
- Thomas Menter
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel
- Matthias Matter
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel
- Jasmin Dionne Haslbauer
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel
- Markus Tolnay
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel
- Kornelia D Galior
- Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin‐Madison School of Medicine and Public Health
- Kristina A Matkwoskyj
- Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin‐Madison School of Medicine and Public Health
- Stephanie M McGregor
- Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin‐Madison School of Medicine and Public Health
- Laura K Muller
- Department of Pathology and Laboratory Medicine, University of Wisconsin Carbone Cancer Center, University of Wisconsin‐Madison School of Medicine and Public Health
- Emad A Rakha
- Division of Cancer and Stem Cells, Department of Pathology, School of Medicine, Nottingham University Hospitals, University of Nottingham
- Antonio Lopez‐Beltran
- Champalimaud Centre for the Unknown
- Ronny Drapkin
- Penn Ovarian Cancer Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania Perelman School of Medicine
- Maximilian Ackermann
- Institute of Pathology and Molecular Pathology, Helios University Clinic Wuppertal, University of Witten/Herdecke
- Paul B Fisher
- Department of Human and Molecular Genetics, School of Medicine, Virginia Commonwealth University
- Steven R Grossman
- Department of Internal Medicine, Keck School of Medicine, Norris Comprehensive Cancer Center
- Andrew K Godwin
- Department of Pathology and Laboratory Medicine, University of Kansas Medical Center
- Arutha Kulasinghe
- The University of Queensland Diamantina Institute, The University of Queensland
- Ivan Martinez
- Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University
- Clay B Marsh
- Department of Microbiology, Immunology & Cell Biology and WVU Cancer Institute, West Virginia University
- Benjamin Tang
- Department of Intensive Care Medicine, Nepean Hospital
- Max S Wicha
- Rogel Cancer Center, University of Michigan
- Kyoung Jae Won
- Biotech Research and Innovation Centre (BRIC), University of Copenhagen
- Alexandar Tzankov
- Pathology, Institute of Medical Genetics and Pathology, University Hospital Basel and University of Basel
- Eduardo Moreno
- Champalimaud Centre for the Unknown
- Rajan Gogna
- Champalimaud Centre for the Unknown
- DOI
- https://doi.org/10.15252/emmm.202013714
- Journal volume & issue
-
Vol. 13,
no. 11
pp. 1 – 17
Abstract
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.
Keywords
