Characterization of METRNβ as a novel biomarker of Coronavirus disease 2019 severity and prognosis

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is increasing worldwide, with complications due to frequent viral mutations, an intricate pathophysiology, and variable host immune responses. Biomarkers with predictive and prognostic value are crucial but lacking. METHODS: Serum samples from authentic and D614G variant (non-Omicron), and Omicron-SARS-CoV-2 infected patients were collected for METRNβ detection and longitudinal cytokine/chemokine analysis. Correlation analyses were performed to compare the relationships between serum METRNβ levels and cytokines/chemokines, laboratory parameters, and disease severity. Receiver operating characteristic (ROC) curves and Kaplan-Meier survival curves were used to evaluate the predictive value of METRNβ in COVID-19. RESULTS: The serum level of METRNβ was highly elevated in non-Omicron-SARS-CoV-2 infected patients compared to healthy individuals, and the non-survivor displayed higher METRNβ levels than survivors among the critical ones. METRNβ concentration showed positive correlation with viral load in NAPS. ROC curve showed that a baseline METRNβ level of 1886.89 pg/ml distinguished COVID-19 patients from non-infected individuals with an AUC of 0.830. Longitudinal analysis of cytokine/chemokine profiles revealed a positive correlation between METRNβ and pro-inflammatory cytokines such as IL6, and an inverse correlation with soluble CD40L (sCD40L). Higher METRNβ was associated with increased mortality. These findings were validated in a second and third cohort of COVID-19 patients identified in a subsequent wave. DISCUSSION: Our study uncovered the precise role of METRNβ in predicting the severity of COVID-19, thus providing a scientific basis for further evaluation of the role of METRNβ in triage therapeutic strategies.