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Flower lose, a cell fitness marker, predicts COVID-19 prognosis #MMPMID34661368
Yekelchyk M; Madan E; Wilhelm J; Short KR; Palma AM; Liao L; Camacho D; Nkadori E; Winters MT; Rice ES; Rolim I; Cruz-Duarte R; Pelham CJ; Nagane M; Gupta K; Chaudhary S; Braun T; Pillappa R; Parker MS; Menter T; Matter M; Haslbauer JD; Tolnay M; Galior KD; Matkwoskyj KA; McGregor SM; Muller LK; Rakha EA; Lopez-Beltran A; Drapkin R; Ackermann M; Fisher PB; Grossman SR; Godwin AK; Kulasinghe A; Martinez I; Marsh CB; Tang B; Wicha MS; Won KJ; Tzankov A; Moreno E; Gogna R
EMBO Mol Med 2021[Nov]; 13 (11): e13714 PMID34661368show ga
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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EMBO+Mol+Med 2021 ; 13 (11): e13714
