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

Yekelchyk, Michail; Madan, Esha; Wilhelm, Jochen; Short, Kirsty R.; Liao, Linbu; Camacho, Denise; Nkadori, Everlyne; Winters, Michael T.; Rice, Emily S.; Rolim, Ines; Cruz-Duarte, 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.; Lopez-Beltran, 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

Publicación: EMBO MOLECULAR MEDICINE
2021
VL / 13 - BP / - EP /
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.

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Gold