The stratification of mortality risk in COVID-19 patients remains extremely challenging for physicians, especially in older patients. Innovative minimally invasive molecular biomarkers are needed to improve the prediction of mortality risk and better customize patient management. In this study, aimed at identifying circulating miRNAs associated with the risk of COVID-19 in-hospital mortality, we analyzed serum samples of 12 COVID-19 patients by small RNA-seq and validated the findings in an independent cohort of 116 COVID-19 patients by qRT-PCR. Thirty-four significantly deregulated miRNAs, 25 downregulated and 9 upregulated in deceased COVID-19 patients compared to survivors, were identified in the discovery cohort. Based on the highest fold-changes and on the highest expression levels, 5 of these 34 miRNAs were selected for the analysis in the validation cohort. MiR-320b and miR-483-5p were confirmed to be significantly hyper-expressed in deceased patients compared to survived ones. Kaplan-Meier and Cox regression models, adjusted for relevant confounders, confirmed that patients with the 20% highest miR-320b and miR-483-5p serum levels had three-fold increased risk to die during in-hospital stay for COVID-19. In conclusion, high levels of circulating miR-320b and miR-483-5p can be useful as minimally invasive biomarkers to stratify older COVID-19 patients with an increased risk of in-hospital mortality.

COVID-19 患者死亡风险的分层对医生来说仍然极具挑战性，尤其是老年患者。需要创新的微创分子生物标志物来改进死亡风险的预测并更好地定制患者管理。在这项研究中，旨在识别与 COVID-19 院内死亡风险相关的循环 miRNA，我们通过小 RNA-seq 分析了 12 名 COVID-19 患者的血清样本，并在 116 名 COVID-19 的独立队列中验证了这些发现患者通过 qRT-PCR。与幸存者相比，已故 COVID-19 患者中有 34 种显着失调的 miRNA，其中 25 种下调，9 种上调。基于最高倍数变化和最高表达水平，选择这 34 种 miRNA 中的 5 种用于验证队列中的分析。与幸存者相比，已证实 MiR-320b 和 miR-483-5p 在已故患者中显着超表达。针对相关混杂因素进行调整后的 Kaplan-Meier 和 Cox 回归模型证实，miR-320b 和 miR-483-5p 血清水平最高 20% 的患者在 COVID-19 住院期间的死亡风险增加了三倍。总之，高水平的循环 miR-320b 和 miR-483-5p 可用作微创生物标志物，用于对院内死亡风险增加的老年 COVID-19 患者进行分层。证实，miR-320b 和 miR-483-5p 血清水平最高 20% 的患者在 COVID-19 住院期间的死亡风险增加了三倍。总之，高水平的循环 miR-320b 和 miR-483-5p 可用作微创生物标志物，用于对院内死亡风险增加的老年 COVID-19 患者进行分层。证实，miR-320b 和 miR-483-5p 血清水平最高 20% 的患者在 COVID-19 住院期间的死亡风险增加了三倍。总之，高水平的循环 miR-320b 和 miR-483-5p 可用作微创生物标志物，用于对院内死亡风险增加的老年 COVID-19 患者进行分层。