Autor: |
Madhvi Menon, Paul M. Kaye, Katherine Newling, Sean Knight, Julie Wilson, Dimitris Lagos, Joanne E. Konkel, Angela Simpson, Nathalie Signoret, John R. Grainger, Chris P Jagger, Elizabeth R. Mann, Tracy Hussell, Kara Filbey, David Kealy, Sally James |
Rok vydání: |
2021 |
Předmět: |
|
DOI: |
10.1101/2021.08.04.21261471 |
Popis: |
Circulating microRNAs (miRNAs) are exceptional mechanism-based correlates of disease, yet their potential remains largely untapped in COVID-19. Here, we determined circulating miRNA and cytokine and chemokine (CC) profiles in 171 blood plasma samples from 58 hospitalised COVID-19 patients. Thirty-two miRNAs were differentially expressed in severe cases when compared to moderate and mild cases. These miRNAs and their predicted targets reflected key COVID-19 features including cell death and hypoxia. Compared to mild cases, moderate and severe cases were characterised by a global decrease in circulating miRNA levels. Partial least squares regression using miRNA and CC measurements allowed for discrimination of severe cases with greater accuracy (87%) than using miRNA or CC levels alone. Correlation analysis revealed severity group-specific associations between CC and miRNA levels. Importantly, the miRNAs that correlated with IL6 and CXCL10, two cardinal COVID-19-associated cytokines, were distinct between severity groups, providing a novel qualitative way to stratify patients with similar levels of proinflammatory cytokines but different disease severity. Integration of miRNA and CC levels with clinical parameters revealed severity-specific signatures associated with clinical hallmarks of COVID-19. Our study highlights the existence of severity-specific circulating CC/miRNA networks, providing insight into COVID-19 pathogenesis and a novel approach for monitoring COVID-19 progression. |
Databáze: |
OpenAIRE |
Externí odkaz: |
|