Jain Ruchi, Ramaswamy Sathishkumar, Harilal Divinlal, Uddin Mohammed, Loney Tom, Nowotny Norbert, Alsuwaidi Hanan, Varghese Rupa, Deesi Zulfa, Alkhajeh Abdulmajeed, Khansaheb Hamda, Alsheikh-Ali Alawi, Abou Tayoun Ahmad
Al Jalila Genomics Center, Al Jalila Children's Hospital, Dubai, United Arab Emirates.
College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates.
Comput Struct Biotechnol J. 2020 Dec 17;19:153-160. doi: 10.1016/j.csbj.2020.12.016. eCollection 2021.
Characterizing key molecular and cellular pathways involved in COVID-19 is essential for disease prognosis and management. We perform shotgun transcriptome sequencing of human RNA obtained from nasopharyngeal swabs of patients with COVID-19, and identify a molecular signature associated with disease severity. Specifically, we identify globally dysregulated immune related pathways, such as cytokine-cytokine receptor signaling, complement and coagulation cascades, JAK-STAT, and TGF- β signaling pathways in all, though to a higher extent in patients with severe symptoms. The excessive release of cytokines and chemokines such as , , and and certain interferons and interleukins related genes like , , and were significantly higher in patients with severe clinical presentation compared to mild and moderate presentations. Differential gene expression analysis identified a small set of regulatory genes that might act as strong predictors of patient outcome. Our data suggest that rapid transcriptome analysis of nasopharyngeal swabs can be a powerful approach to quantify host molecular response and may provide valuable insights into COVID-19 pathophysiology.
确定参与2019冠状病毒病(COVID-19)的关键分子和细胞途径对于疾病的预后和管理至关重要。我们对从COVID-19患者鼻咽拭子中获取的人类RNA进行鸟枪法转录组测序,并确定与疾病严重程度相关的分子特征。具体而言,我们发现免疫相关途径在整体上存在失调,如细胞因子-细胞因子受体信号传导、补体和凝血级联反应、JAK-STAT以及TGF-β信号通路,不过在重症患者中失调程度更高。与轻症和中症患者相比,重症患者中细胞因子和趋化因子如 、 、 和 以及某些干扰素和白细胞介素相关基因如 、 、 和 的过度释放明显更高。差异基因表达分析确定了一小部分调控基因,它们可能是患者预后的有力预测指标。我们的数据表明,对鼻咽拭子进行快速转录组分析可能是量化宿主分子反应的有效方法,并可能为COVID-19的病理生理学提供有价值的见解。