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.
- Yekelchyk, M.
- Madan, E.
- Wilhelm, J.
- Short, K. R.
- Palma, A. M.
- Liao, L.
- Camacho, D.
- Nkadori, E.
- Winters, M. T.
- Rice, E. S.
- Rolim, I.
- Cruz-Duarte, R.
- Pelham, C. J.
- Nagane, M.
- Gupta, K.
- Chaudhary, S.
- Braun, T.
- Pillappa, R.
- Parker, M. S.
- Menter, T.
- Matter, M.
- Haslbauer, J. D.
- Tolnay, M.
- Galior, K. D.
- Matkwoskyj, K. A.
- McGregor, S. M.
- Muller, L. K.
- Rakha, E. A.
- Lopez-Beltran, A.
- Drapkin, R.
- Ackermann, M.
- Fisher, P. B.
- Grossman, S. R.
- Godwin, A. K.
- Kulasinghe, A.
- Martinez, I.
- Marsh, C. B.
- Tang, B.
- Wicha, M. S.
- Won, K. J.
- Tzankov, A.
- Moreno, E.
- Gogna, R.
Keywords
- Covid-19
- biomarker
- cell fitness
- flower
- prognosis
