Differential Expression of Viral Transcripts From Single-Cell RNA Sequencing of Moderate and Severe COVID-19 Patients and Its Implications for Case Severity.
Differential Expression of Viral Transcripts From Single-Cell RNA Sequencing of Moderate and Severe COVID-19 Patients and Its Implications for Case Severity.
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DOI：
10.3389/fmicb.2020.603509
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发表时间：
2020
影响因子：
5.2
通讯作者：
Zhao Z
中科院分区：
文献类型：
--
作者：
Liu T;Jia P;Fang B;Zhao Z
随着全球（尤其是美国）新增COVID-19病例稳步增加，疫情爆发地区的医疗资源因大量COVID-19患者而迅速耗尽。因此，迫切需要能够有效和快速地预测疾病进展并对患者进行分层以进行适当的医疗保健安排的策略。我们使用单细胞和大量组织转录组数据，探索了来自中重度COVID-19患者支气管肺泡灌洗液的SARS-CoV-2感染细胞中病毒基因表达的特征和进化差异。我们发现SARS-CoV-2序列在8种免疫相关细胞中可检测到，包括巨噬细胞、T细胞和NK细胞。我们首次报道了SARS-CoV-2 ORF 10基因在重度与中度样本中的差异表达。特别是，ORF 10在严重病例的感染细胞中大量表达，而在中度病例的感染细胞中几乎检测不到。因此，ORF 10与核衣壳（N）的表达比率在重度病例中显著高于中度病例（p = 0.0062）。此外，我们还发现了与SARS冠状病毒基因组1073位5'连接点的病毒前导序列非依赖性融合体的转录调节序列（TRS）主要在有死亡结局的患者中检测到，提示其可能的临床结局指示。最后，我们鉴定了SARS-CoV-2病毒前导序列依赖的融合事件的TRS模体，并与SARS-CoV的TRS模体进行了比较，推测了其进化轨迹。这些结果暗示了病毒转录本在COVID-19中度和重度患者发病机制中的潜在作用和预测特征。这些特征和进化模式需要更多的数据来验证。
With steady increase of new COVID-19 cases around the world, especially in the United States, health care resources in areas with the disease outbreak are quickly exhausted by overwhelming numbers of COVID-19 patients. Therefore, strategies that can effectively and quickly predict the disease progression and stratify patients for appropriate health care arrangements are urgently needed. We explored the features and evolutionary difference of viral gene expression in the SARS-CoV-2 infected cells from the bronchoalveolar lavage fluids of patients with moderate and severe COVID-19 using both single cell and bulk tissue transcriptome data. We found SARS-CoV-2 sequences were detectable in 8 types of immune related cells, including macrophages, T cells, and NK cells. We first reported that the SARS-CoV-2 ORF10 gene was differentially expressed in the severe vs. moderate samples. Specifically, ORF10 was abundantly expressed in infected cells of severe cases, while it was barely detectable in the infected cells of moderate cases. Consequently, the expression ratio of ORF10 to nucleocapsid (N) was significantly higher in severe than moderate cases (p = 0.0062). Moreover, we found transcription regulatory sequences (TRSs) of the viral leader sequence-independent fusions with a 5’ joint point at position 1073 of SARS-CoV-2 genome were detected mainly in the patients with death outcome, suggesting its potential indication of clinical outcome. Finally, we identified the motifs in TRS of the viral leader sequence-dependent fusion events of SARS-CoV-2 and compared with that in SARS-CoV, suggesting its evolutionary trajectory. These results implicated potential roles and predictive features of viral transcripts in the pathogenesis of COVID-19 moderate and severe patients. Such features and evolutionary patterns require more data to validate in future.
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DOI：
10.7759/cureus.12067
发表时间：
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期刊：
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影响因子：
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