Plasma miRNA profile at COVID-19 onset predicts severity status and mortality

Asier Fernandez-Pato, Ana Virseda-Berdices, Salvador Resino, Pablo Ryan, Oscar Martinez-Gonzalez, Felipe Perez-Garcia, Maria Martin-Vicente, Daniel Valle-Millares, Oscar Brochado-Kith, Rafael Blancas, Amalia Martinez, Francisco C. Ceballos, Sofia Bartolome-Sanchez, Erick Joan Vidal-Alcantara, David Alonso, Natalia Blanca-Lopez, Ignacio Ramirez Martinez-Acitores, Laura Martin-Pedraza, Maria Angeles Jimenez-Sousa*, Amanda Fernandez-Rodriguez

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    41 Citations (Scopus)
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    Abstract

    Background: MicroRNAs (miRNAs) have a crucial role in regulating immune response against infectious diseases, showing changes early in disease onset and before the detection of the pathogen. Thus, we aimed to analyze the plasma miRNA profile at COVID-19 onset to identify miRNAs as early prognostic biomarkers of severity and survival.

    Methods and results: Plasma miRNome of 96 COVID-19 patients that developed asymptomatic/mild, moderate and severe disease was sequenced together with a group of healthy controls. Plasma immune-related biomarkers were also assessed. COVID-19 patients showed 200 significant differentially expressed (SDE) miRNAs concerning healthy controls, with upregulated putative targets of SARS-CoV-2, and inflammatory miRNAs. Among COVID-19 patients, 75 SDE miRNAs were observed in asymptomatic/mild compared to symptomatic patients, which were involved in platelet aggregation and cytokine pathways, among others. Moreover, 137 SDE miRNAs were identified between severe and moderate patients, where miRNAs targeting the SARS CoV-2 genome were the most strongly disrupted. Finally, we constructed a mortality predictive risk score (miRNA-MRS) with ten miRNAs. Patients with higher values had a higher risk of 90-days mortality (hazard ratio = 4.60; p-value < 0.001). Besides, the discriminant power of miRNA-MRS was significantly higher than the observed for age and gender (AUROC = 0.970 vs. 0.881; p = 0.042).

    Conclusions: SARS-CoV-2 infection deeply disturbs the plasma miRNome from an early stage of COVID-19, making miRNAs highly valuable as early predictors of severity and mortality.

    Original languageEnglish
    Pages (from-to)676-688
    Number of pages13
    JournalEmerging microbes & infections
    Volume11
    Issue number1
    DOIs
    Publication statusPublished - 2022

    Keywords

    • SARS-CoV2
    • COVID-19
    • miRNAs
    • severity
    • mortality
    • VIRUS-INFECTION
    • EXPRESSION
    • MICRORNAS
    • MIR-150

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