Background Extracellular vesicles (EVs), containing microRNAs (miRNAs) and other molecules, play a central role in intercellular communication, especially in viral infections caused by SARS-CoV-2. This study explores the miRNA profiles in plasma-derived EVs from severe COVID-19 patients referred to controls, identifying potential mortality miRNA predictors. Methods A prospective study was carried out, including 36 severe COVID-19 patients and 33 non-COVID-19 controls. EVs-derived miRNAs were sequenced, and bioinformatics and differential expression analysis between groups were performed. The plasma miRNA profile of an additional cohort of severe COVID-19 patients (n=32) and non-COVID-19 controls (n=12) was used to compare with our data. Survival analysis was used to identify potential mortality predictors among the SDE miRNAs in EVs. Results Severe COVID-19 patients showed 50 significantly differentially expressed (SDE) miRNAs in plasma-derived EVs. These miRNAs were associated with pathways related to inflammation and cell adhesion. Fifteen of these plasma-derived EVs miRNAs were also SDE in the plasma of severe patients vs controls. Two miRNAs, hsa-miR-1469 and hsa-miR-6124, were identified as strong mortality predictors with an área under the ROC Curve (AUC) of 0.938. Conclusion : This research provides insights into the role of miRNAs found within EVs in severe COVID-19 and their potential as clinical biomarkers for mortality.

中文翻译：

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重症 COVID-19 患者细胞外囊泡的 miRNome 分析和死亡预测因子的鉴定


背景 含有 microRNA （miRNA） 和其他分子的细胞外囊泡 （EV） 在细胞间通讯中起着核心作用，尤其是在 SARS-CoV-2 引起的病毒感染中。本研究探讨了转诊至对照组的严重 COVID-19 患者的血浆衍生 EV 中的 miRNA 谱，确定了潜在的死亡率 miRNA 预测因子。方法 进行了一项前瞻性研究，包括 36 名重症 COVID-19 患者和 33 名非 COVID-19 对照者。对 EVs 来源的 miRNAs 进行测序，进行生物信息学和组间差异表达分析。使用另一组重症 COVID-19 患者 （n=32） 和非 COVID-19 对照 （n=12） 的血浆 miRNA 谱与我们的数据进行比较。生存分析用于确定 EV 中 SDE miRNAs 中的潜在死亡率预测因子。结果 重症 COVID-19 患者在血浆来源的 EVs 中显示出 50 个显著差异表达 （SDE） miRNA。这些 miRNAs 与炎症和细胞粘附相关的通路相关。与对照组相比，这些血浆来源的 EVs miRNA 中有 15 个在重症患者血浆中也是 SDE。两种 miRNA，hsa-miR-1469 和 hsa-miR-6124，被确定为强死亡率预测因子，ROC 曲线下 área （AUC） 为 0.938。结论： 本研究深入了解了 EV 中发现的 miRNA 在严重 COVID-19 中的作用及其作为死亡率临床生物标志物的潜力。