Comment on 'SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung'.
Comment on 'SARS-CoV-2 suppresses anticoagulant and fibrinolytic gene expression in the lung'.
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DOI：
10.7554/elife.74268
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发表时间：
2022-01-11
期刊：
影响因子：
7.7
通讯作者：
Jamieson AM
中科院分区：
文献类型：
--
作者：
FitzGerald ES;Jamieson AM
Mast等人。分析了新冠肺炎患者支气管肺泡灌洗液样本的转录组数据，这些样本来自一项研究肥胖和哮喘成人中微生物群和炎症相互作用的RNA-SEQ样本(Mast等人，2021年)。基于他们对这些数据的分析，马斯特等人。结论：新冠肺炎患者外源性凝血级联和纤溶关键调节因子的基因表达显著降低。值得注意的是，他们报告说，外源性凝血级联主要调节因子组织因子(F3)的表达保持不变，而其同源抑制物组织因子途径抑制物(TFPI)的表达上调了8倍。由此，他们得出结论：“肺纤维蛋白沉积并非源于局部[组织因子]生成的增加，而与直觉相反，新冠肺炎可能会抑制肺内[组织因子]依赖的机制”。他们还报道了活化蛋白C(APC)介导的抗凝活性降低，纤维蛋白原表达和血栓形成的其他关键调节因子显著增加。这些结果中的许多与大多数领域的发现相矛盾，特别是关于外源性凝血级联介导的凝血疾病的发现。在这里，我们提出了对Mast等人分析的数据集的完整重新分析。这种重新分析表明，所使用的两个数据集彼此之间不具有可比性，并且新冠肺炎样本集不适合Mast等人的转录本分析。已执行。我们还发现了他们的回顾分析设计中的其他重大缺陷，如质量控制和过滤标准不佳。考虑到数据集和分析存在的问题，他们的结论不被支持。
Mast et al. analyzed transcriptome data derived from RNA-sequencing (RNA-seq) of COVID-19 patient bronchoalveolar lavage fluid (BALF) samples, as compared to BALF RNA-seq samples from a study investigating microbiome and inflammatory interactions in obese and asthmatic adults (Mast et al., 2021). Based on their analysis of these data, Mast et al. concluded that mRNA expression of key regulators of the extrinsic coagulation cascade and fibrinolysis were significantly reduced in COVID-19 patients. Notably, they reported that the expression of the extrinsic coagulation cascade master regulator Tissue Factor (F3) remained unchanged, while there was an 8-fold upregulation of its cognate inhibitor Tissue Factor Pathway Inhibitor (TFPI). From this they conclude that “pulmonary fibrin deposition does not stem from enhanced local [tissue factor] production and that counterintuitively, COVID-19 may dampen [tissue factor]-dependent mechanisms in the lungs”. They also reported decreased Activated Protein C (aPC) mediated anticoagulant activity and major increases in fibrinogen expression and other key regulators of clot formation. Many of these results are contradictory to findings in most of the field, particularly the findings regarding extrinsic coagulation cascade mediated coagulopathies. Here, we present a complete re-analysis of the data sets analyzed by Mast et al. This re-analysis demonstrates that the two data sets utilized were not comparable between one another, and that the COVID-19 sample set was not suitable for the transcriptomic analysis Mast et al. performed. We also identified other significant flaws in the design of their retrospective analysis, such as poor-quality control and filtering standards. Given the issues with the datasets and analysis, their conclusions are not supported.