FitzGerald Ethan S, Jamieson Amanda M
Division of Biology and Medicine, Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island, United States.
bioRxiv. 2020 Jul 7:2020.07.06.182972. doi: 10.1101/2020.07.06.182972.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has rapidly become a global pandemic. In addition to the acute pulmonary symptoms of COVID-19 (the disease associated with SARS-CoV-2 infection), pulmonary and distal coagulopathies have caused morbidity and mortality in many patients. Currently, the molecular pathogenesis underlying COVID-19 associated coagulopathies are unknown. While there are many theories for the cause of this pathology, including hyper inflammation and excess tissue damage, the cellular and molecular underpinnings are not yet clear. By analyzing transcriptomic data sets from experimental and clinical research teams, we determined that changes in the gene expression of genes important in the extrinsic coagulation cascade in the lung epithelium may be important triggers for COVID-19 coagulopathy. This regulation of the extrinsic blood coagulation cascade is not seen with influenza A virus (IAV)-infected NHBEs suggesting that the lung epithelial derived coagulopathies are specific to SARS-Cov-2 infection. This study is the first to identify potential lung epithelial cell derived factors contributing to COVID-19 associated coagulopathy.
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)迅速成为全球大流行病。除了COVID-19(与SARS-CoV-2感染相关的疾病)的急性肺部症状外,肺部和远端凝血功能障碍已导致许多患者发病和死亡。目前,COVID-19相关凝血功能障碍的分子发病机制尚不清楚。虽然对于这种病理状况的成因有许多理论,包括过度炎症和过度组织损伤,但细胞和分子基础仍不明确。通过分析来自实验和临床研究团队的转录组数据集,我们确定肺上皮细胞中外源性凝血级联反应中重要基因的基因表达变化可能是COVID-19凝血功能障碍的重要触发因素。甲型流感病毒(IAV)感染的人正常支气管上皮细胞(NHBEs)未出现外源性凝血级联反应的这种调节,这表明肺上皮细胞衍生的凝血功能障碍是SARS-CoV-2感染所特有的。本研究首次确定了可能导致COVID-19相关凝血功能障碍的肺上皮细胞衍生因子。