Tang Hao, Gao Yuehan, Li Zhaohuai, Miao Yushan, Huang Zhaohao, Liu Xiuxing, Xie Lihui, Li He, Wen Wen, Zheng Yingfeng, Su Wenru
Department of Respiratory and Critical Care Medicine Changzheng Hospital, Second Military Medical University, Shanghai, China.
Department of Critical Care, Wuhan Huo Shen Shan Hospital, Hubei, China.
Clin Transl Med. 2020 Oct;10(6):e200. doi: 10.1002/ctm2.200.
COVID-19 is currently a global pandemic, but the response of human immune system to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection remains unclear. Noncoding RNAs serve as immune regulators and thus may play a critical role in disease progression.
We performed multi-transcriptome sequencing of both noncoding RNAs and mRNAs isolated from the red blood cell depleted whole blood of moderate and severe COVID-19 patients. The functions of noncoding RNAs were validated by analyses of the expression of downstream mRNAs. We further utilized the single-cell RNA-seq data of COVID-19 patients from Wilk et al. and Chua et al. to characterize noncoding RNA functions in different cell types.
We defined four types of microRNAs with different expression tendencies that could serve as biomarkers for COVID-19 progress. We also identified miR-146a-5p, miR-21-5p, miR-142-3p, and miR-15b-5p as potential contributors to the disease pathogenesis, possibly serving as biomarkers of severe COVID-19 and as candidate therapeutic targets. In addition, the transcriptome profiles consistently suggested hyperactivation of the immune response, loss of T-cell function, and immune dysregulation in severe patients.
Collectively, these findings provide a comprehensive view of the noncoding and coding transcriptional landscape of peripheral immune cells during COVID-19, furthering our understanding and offering novel insights into COVID-19 pathogenesis.
新型冠状病毒肺炎（COVID-19）目前是一种全球大流行病，但人类免疫系统对严重急性呼吸综合征冠状病毒2（SARS-CoV-2）感染的反应仍不清楚。非编码RNA作为免疫调节因子，因此可能在疾病进展中起关键作用。
我们对从COVID-19中重度患者去除红细胞的全血中分离出的非编码RNA和mRNA进行了多转录组测序。通过分析下游mRNA的表达来验证非编码RNA的功能。我们进一步利用了威尔克等人和蔡等人提供的COVID-19患者的单细胞RNA测序数据，以表征非编码RNA在不同细胞类型中的功能。
我们定义了四种具有不同表达趋势的微小RNA，它们可作为COVID-19进展的生物标志物。我们还确定了miR-146a-5p、miR-21-5p、miR-142-3p和miR-15b-5p是疾病发病机制的潜在促成因素，可能作为重症COVID-19的生物标志物和候选治疗靶点。此外，转录组图谱一致表明重症患者免疫反应过度激活、T细胞功能丧失和免疫失调。
总体而言，这些发现提供了COVID-19期间外周免疫细胞非编码和编码转录景观的全面视图，加深了我们对COVID-19发病机制的理解并提供了新的见解。
