Deep RNA sequencing of intensive care unit patients with COVID-19.

Deep RNA sequencing of intensive care unit patients with COVID-19.
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DOI:
10.1038/s41598-022-20139-1
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发表时间:
2022-09-21
期刊:
影响因子:
4.6
通讯作者:
Monaghan, Sean F.
Monaghan, Sean F.
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fredericks, Alger M.;Jentzsch, Maximilian S.;Cioffi, William G.;Cohen, Maya;Fairbrother, William G.;Gandhi, Shivam J.;Harrington, Elizabeth O.;Nau, Gerard J.;Reichner, Jonathan S.;Ventetuolo, Corey E.;Levy, Mitchell M.;Ayala, Alfred;Monaghan, Sean F.

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COVID-19影响了全球数百万患者。现在进行的分子检测可以在采样部位识别病毒的存在:鼻咽、鼻孔或口腔。RNA测序有可能确定病毒的存在并确定宿主对COVID-19的反应。对入住重症监护室的COVID-19患者进行的单中心前瞻性研究,其中对外周血进行了深度RNA测序(> 1亿次读取),并进行了计算生物学分析。所有患者均为SARS-CoV-2 PCR阳性。前瞻性收集临床数据。我们在一家医院招募了15名患者。患者病情危重,死亡率为47%,67%使用呼吸机。除了来自其他病毒、细菌和古细菌的RNA外,所有患者的血液中都检测到了SARS-CoV-2 RNA。许多免疫调节基因的表达,包括PD-L1和PD-L2,在死于COVID-19的患者中存在显著差异。一些蛋白质受到选择性转录和剪接事件的影响,如在HLA-C、HLA-E、NRP 1和NRP 2中所见。根据可变RNA剪接和转录起始/结束计算的熵预测了这些患者的死亡率。目前对COVID-19的上呼吸道检测只能确定病毒是否存在。使用适当的计算生物学进行深度RNA测序可以提供重要的预后信息,并指出在未来研究中精确靶向的治疗病灶。
COVID-19 has impacted millions of patients across the world. Molecular testing occurring now identifies the presence of the virus at the sampling site: nasopharynx, nares, or oral cavity. RNA sequencing has the potential to establish both the presence of the virus and define the host’s response in COVID-19. Single center, prospective study of patients with COVID-19 admitted to the intensive care unit where deep RNA sequencing (> 100 million reads) of peripheral blood with computational biology analysis was done. All patients had positive SARS-CoV-2 PCR. Clinical data was prospectively collected. We enrolled fifteen patients at a single hospital. Patients were critically ill with a mortality of 47% and 67% were on a ventilator. All the patients had the SARS-CoV-2 RNA identified in the blood in addition to RNA from other viruses, bacteria, and archaea. The expression of many immune modulating genes, including PD-L1 and PD-L2, were significantly different in patients who died from COVID-19. Some proteins were influenced by alternative transcription and splicing events, as seen in HLA-C, HLA-E, NRP1 and NRP2. Entropy calculated from alternative RNA splicing and transcription start/end predicted mortality in these patients. Current upper respiratory tract testing for COVID-19 only determines if the virus is present. Deep RNA sequencing with appropriate computational biology may provide important prognostic information and point to therapeutic foci to be precisely targeted in future studies.
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期刊: Science (New York, N.Y.)
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