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Journal Article

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


Yekelchyk,  Michail
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;


Braun,  Thomas
Cardiac Development and Remodeling, Max Planck Institute for Heart and Lung Research, Max Planck Society;

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Yekelchyk, M., Madan, E., Wilhelm, J., Short, K. R., Liao, L., Camacho, D., et al. (2021). Flower lose, a cell fitness marker, predicts COVID-19 prognosis. EMBO MOLECULAR MEDICINE, e13714. doi:10.15252/emmm.202013714.

Cite as: http://hdl.handle.net/21.11116/0000-0009-6A3D-D
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.