Summary Inflammatory cytokines and chemokines (CC) drive COVID-19 pathology. Yet, patients with similar circulating CC levels present with different disease severity. Here, we determined 171 microRNAomes from 58 hospitalized COVID-19 patients (Cohort 1) and levels of 25 cytokines and chemokines (CC) in the same samples. Combining microRNA (miRNA) and CC measurements allowed for discrimination of severe cases with greater accuracy than using miRNA or CC levels alone. Severity group-specific associations between miRNAs and COVID-19-associated CC (e.g., IL6, CCL20) or clinical hallmarks of COVID-19 (e.g., neutrophilia, hypoalbuminemia) separated patients with similar CC levels but different disease severity. Analysis of an independent cohort of 108 patients from a different center (Cohort 2) demonstrated feasibility of CC/miRNA profiling in leftover hospital blood samples with similar severe disease CC and miRNA profiles, and revealed CCL20, IL6, IL10, and miR-451a as key correlates of fatal COVID-19. These findings highlight that systemic miRNA/CC networks underpin severe COVID-19. Graphical abstract Highlights • MiRNA and CC profiles of 166 COVID-19 patients, including a leftover blood cohort • Combining miRNA and CC profiling improves discrimination of severe COVID-19 cases • Severity group-specific miRNA correlates of COVID-19-linked CC and clinical features • 8 CC/3 miRNA signature of fatal COVID-19, including CCL20, IL6, IL10, and miR-451a Health sciences; Clinical finding; Complex system biology
【저자키워드】 Health Sciences, Clinical finding, Complex system biology, 【초록키워드】 COVID-19, severe COVID-19, feasibility, disease severity, hospital, microRNA, miRNA, IL6, cytokine, chemokine, Cohort, Accuracy, clinical, Patient, clinical feature, COVID-19 patients, Blood, association, hospitalized COVID-19 patient, severe disease, CCL20, complex system, Abstract, profile, blood sample, Severe case, circulating, miRNA signature, hallmark, COVID-19 pathology, fatal COVID-19, IL10, independent, highlight, miRNA profiles, IMPROVE, greater, demonstrated, separated, 【제목키워드】 COVID-19, change, fatality, reveal,