EMBO Molecular Medicine (Nov 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 Bad Nauheim Germany
- Esha Madan
- Champalimaud Centre for the Unknown Lisbon Portugal
- Jochen Wilhelm
- Universities Giessen & Marburg Lung Center German Center for Lung Research (DZL) Justus‐Liebig‐University Giessen Germany
- Kirsty R Short
- School of Chemistry and Molecular Biosciences The University of Queensland Brisbane Qld Australia
- António M Palma
- Champalimaud Centre for the Unknown Lisbon Portugal
- Linbu Liao
- Biotech Research and Innovation Centre (BRIC) University of Copenhagen Copenhagen N Denmark
- Denise Camacho
- Champalimaud Centre for the Unknown Lisbon Portugal
- Everlyne Nkadori
- Department of Pathology and Laboratory Medicine University of Wisconsin Carbone Cancer Center University of Wisconsin‐Madison School of Medicine and Public Health Madison WI USA
- Michael T Winters
- Department of Microbiology Immunology & Cell Biology and WVU Cancer Institute West Virginia University Morgantown WV USA
- Emily S Rice
- Department of Microbiology Immunology & Cell Biology and WVU Cancer Institute West Virginia University Morgantown WV USA
- Inês Rolim
- Champalimaud Centre for the Unknown Lisbon Portugal
- Raquel Cruz‐Duarte
- Instituto de Medicina Molecular João Lobo Antunes Faculdade de Medicina Universidade de Lisboa Lisboa Portugal
- Christopher J Pelham
- Eurofins Panlabs Inc. St. Charles MO USA
- Masaki Nagane
- Department of Biochemistry School of Veterinary Medicine Azabu University Kanagawa Japan
- Kartik Gupta
- Department of Surgery School of Medicine and Public Health University of Wisconsin Madison WI USA
- Sahil Chaudhary
- Department of Surgery School of Medicine and Public Health University of Wisconsin Madison WI USA
- Thomas Braun
- Department of Cardiac Development and Remodelling Max Planck Institute for Heart and Lung Research Bad Nauheim Germany
- Raghavendra Pillappa
- Department of Pathology Virginia Commonwealth University School of Medicine Richmond VA USA
- 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 Richmond VA USA
- Thomas Menter
- Pathology, Institute of Medical Genetics and Pathology University Hospital Basel and University of Basel Basel Switzerland
- Matthias Matter
- Pathology, Institute of Medical Genetics and Pathology University Hospital Basel and University of Basel Basel Switzerland
- Jasmin Dionne Haslbauer
- Pathology, Institute of Medical Genetics and Pathology University Hospital Basel and University of Basel Basel Switzerland
- Markus Tolnay
- Pathology, Institute of Medical Genetics and Pathology University Hospital Basel and University of Basel Basel Switzerland
- 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 Madison WI USA
- 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 Madison WI USA
- 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 Madison WI USA
- 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 Madison WI USA
- Emad A Rakha
- Division of Cancer and Stem Cells Department of Pathology School of Medicine Nottingham University Hospitals University of Nottingham Nottingham UK
- Antonio Lopez‐Beltran
- Champalimaud Centre for the Unknown Lisbon Portugal
- Ronny Drapkin
- Penn Ovarian Cancer Research Center Department of Obstetrics and Gynecology University of Pennsylvania Perelman School of Medicine Philadelphia PA USA
- Maximilian Ackermann
- Institute of Pathology and Molecular Pathology Helios University Clinic Wuppertal University of Witten/Herdecke Wuppertal Germany
- Paul B Fisher
- Department of Human and Molecular Genetics School of Medicine Virginia Commonwealth University Richmond VA USA
- Steven R Grossman
- Department of Internal Medicine Keck School of Medicine Norris Comprehensive Cancer Center Los Angeles CA USA
- Andrew K Godwin
- Department of Pathology and Laboratory Medicine University of Kansas Medical Center Kansas City KS USA
- Arutha Kulasinghe
- The University of Queensland Diamantina Institute The University of Queensland Brisbane Qld Australia
- Ivan Martinez
- Department of Microbiology Immunology & Cell Biology and WVU Cancer Institute West Virginia University Morgantown WV USA
- Clay B Marsh
- Department of Microbiology Immunology & Cell Biology and WVU Cancer Institute West Virginia University Morgantown WV USA
- Benjamin Tang
- Department of Intensive Care Medicine Nepean Hospital Penrith NSW Australia
- Max S Wicha
- Rogel Cancer Center University of Michigan Ann Arbor MI USA
- Kyoung Jae Won
- Biotech Research and Innovation Centre (BRIC) University of Copenhagen Copenhagen N Denmark
- Alexandar Tzankov
- Pathology, Institute of Medical Genetics and Pathology University Hospital Basel and University of Basel Basel Switzerland
- Eduardo Moreno
- Champalimaud Centre for the Unknown Lisbon Portugal
- Rajan Gogna
- Champalimaud Centre for the Unknown Lisbon Portugal
- DOI
- https://doi.org/10.15252/emmm.202013714
- Journal volume & issue
-
Vol. 13,
no. 11
pp. n/a – n/a
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