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

DOI
https://doi.org/10.15252/emmm.202013714
Journal volume & issue
Vol. 13, no. 11
pp. n/a – n/a

Abstract

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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