Platelet gene expression and function in patients with COVID-19
Platelet gene expression and function in patients with COVID-19
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DOI：
10.1182/blood.2020007214
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发表时间：
2020-09-10
期刊：
影响因子：
20.3
通讯作者：
Campbell, Robert A.
中科院分区：
文献类型：
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作者：
Manne, Bhanu Kanth;Denorme, Frederik;Campbell, Robert A.
目前迫切需要了解2019冠状病毒病（COVID-19）的发病机制。特别是，COVID-19患者的血栓性并发症很常见，并会导致器官衰竭和死亡。严重COVID-19患者存在类似于与败血症相关的弥散性血管内凝血病的止血异常，主要区别在于血栓形成风险增加，而不是出血风险增加。然而，严重急性呼吸综合征冠状病毒2 （SARS-CoV-2）感染是否会改变血小板功能以促进COVID-19的病理生理尚不清楚。在这项研究中，我们报道了SARS-CoV-2感染患者血小板基因表达和功能反应的改变。RNA测序显示COVID-19患者循环血小板基因表达谱发生明显变化。通路分析揭示了与蛋白质泛素化、抗原呈递和线粒体相关的通路的差异基因表达变化！功能障碍。血小板中的信使RNA （mRNA）或蛋白未检测到SARS-CoV-2结合受体血管紧张素转换酶2 （ACE2）。令人惊讶的是，在25名COVID-19患者中的2名患者的血小板中检测到sars - cov - N1基因的mRNA，这表明血小板可能独立于ACE2吸收SARS-CoV-2 mRNA。COVID-19患者静息血小板在基础和激活后p -选择素表达升高。与健康供者相比，COVID-19患者循环血小板-中性粒细胞、-单核细胞和- t细胞聚集量均显著升高。此外，COVID-19患者的血小板聚集速度更快，在纤维蛋白原和胶原蛋白上的扩散都有所增加。血小板活化和聚集的增加可能部分归因于MAPK通路活化和血栓素生成的增加。这些发现表明，SARS-CoV-2感染与血小板高反应性相关，这可能有助于COVID-19的病理生理。
There is an urgent need to understand the pathogenesis of coronavirus disease 2019 (COVID-19). In particular, thrombotic complications in patients with COVID-19 are common and contribute to organ failure and mortality. Patients with severe COVID-19 present with hemostatic abnormalities that mimic disseminated intravascular coagulopathy associated with sepsis, with the major difference being increased risk of thrombosis rather than bleeding. However, whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection alters platelet function to contribute to the pathophysiology of COVID-19 remains unknown. In this study, we report altered platelet gene expression and functional responses in patients infected with SARS-CoV-2. RNA sequencing demonstrated distinct changes in the gene-expression profile of circulating platelets of COVID-19 patients. Pathway analysis revealed differential gene-expression changes in pathways associated with protein ubiquitination, antigen presentation, and mitochondria! dysfunction. The receptor for SARS-CoV-2 binding, angiotensin-converting enzyme 2 (ACE2), was not detected by messenger RNA (mRNA) or protein in platelets. Surprisingly, mRNA from the SARS-CoV-2 N1 gene was detected in platelets from 2 of 25 COVID-19 patients, suggesting that platelets may take-up SARS-COV-2 mRNA independent of ACE2. Resting platelets from COVID-19 patients had increased P-selectin expression basally and upon activation. Circulating platelet-neutrophil, -monocyte, and -T-cell aggregates were all significantly elevated in COVID-19 patients compared with healthy donors. Furthermore, platelets from COVID-19 patients aggregated faster and showed increased spreading on both fibrinogen and collagen. The increase in platelet activation and aggregation could partially be attributed to increased MAPK pathway activation and thromboxane generation. These findings demonstrate that SARS-CoV-2 infection is associated with platelet hyperreactivity, which may contribute to COVID-19 pathophysiology.