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

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 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

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.