Open AccessFlower lose, a cell fitness marker, predicts COVID‐19 prognosis
Author(s) -
Yekelchyk Michail,
Madan Esha,
Wilhelm Jochen,
Short Kirsty R,
Palma António M,
Liao Linbu,
Camacho Denise,
Nkadori Everlyne,
Winters Michael T,
Rice Emily S,
Rolim Inês,
CruzDuarte Raquel,
Pelham Christopher J,
Nagane Masaki,
Gupta Kartik,
Chaudhary Sahil,
Braun Thomas,
Pillappa Raghavendra,
Parker Mark S,
Menter Thomas,
Matter Matthias,
Haslbauer Jasmin Dionne,
Tolnay Markus,
Galior Kornelia D,
Matkwoskyj Kristina A,
McGregor Stephanie M,
Muller Laura K,
Rakha Emad A,
LopezBeltran Antonio,
Drapkin Ronny,
Ackermann Maximilian,
Fisher Paul B,
Grossman Steven R,
Godwin Andrew K,
Kulasinghe Arutha,
Martinez Ivan,
Marsh Clay B,
Tang Benjamin,
Wicha Max S,
Won Kyoung Jae,
Tzankov Alexandar,
Moreno Eduardo,
Gogna Rajan
Publication year - 2021
Publication title -
embo molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.923
H-Index - 107
eISSN - 1757-4684
pISSN - 1757-4676
DOI - 10.15252/emmm.202013714
Subject(s) - medicine , biomarker , triage , receiver operating characteristic , covid-19 , immunology , disease , emergency medicine , biology , infectious disease (medical specialty) , biochemistry
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.