Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity.
Extracellular vesicle-mediated endothelial apoptosis and EV-associated proteins correlate with COVID-19 disease severity.
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DOI：
10.1002/jev2.12117
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发表时间：
2021-07
影响因子：
16
通讯作者：
Dhillon NK
中科院分区：
文献类型：
--
作者：
Krishnamachary B;Cook C;Kumar A;Spikes L;Chalise P;Dhillon NK
由新型严重急性呼吸综合征冠状病毒-2(SARS-CoV-2)引起的冠状病毒病-2019年(新冠肺炎)已导致全球大流行，感染和死亡人数不断上升。更好地了解其发病机制将极大地改善患者的预后和治疗。在这里，我们比较了84名感染SARS-CoV-2的不同疾病严重程度的住院患者循环中大小细胞外小泡(EV)的炎症和心血管疾病相关蛋白含量。我们的发现显示EVS中的促炎、促凝血、免疫调节和组织重塑蛋白信号显著丰富，这些特征显著区分了有症状的新冠肺炎患者与匹配的合并症的未感染对照组，并区分了中度疾病和危重疾病的患者。具体地说，愤怒，其次是Tf和IL-18R1，与疾病严重程度和住院时间显示出最强的相关性。重要的是，新冠肺炎患者的EVS按疾病严重程度诱导肺微血管内皮细胞凋亡。总之，我们的发现支持肠道病毒在新冠肺炎病的发病机制中的作用，并为基于肠道病毒的方法的开发奠定了基础，以预测疾病严重程度，确定患者住院的需求，并确定新的治疗靶点。
Coronavirus disease‐2019 (COVID‐19), caused by the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has lead to a global pandemic with a rising toll in infections and deaths. Better understanding of its pathogenesis will greatly improve the outcomes and treatment of affected patients. Here we compared the inflammatory and cardiovascular disease‐related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS‐CoV‐2 with different stages of disease severity. Our findings reveal significant enrichment of proinflammatory, procoagulation, immunoregulatory and tissue‐remodelling protein signatures in EVs, which remarkably distinguished symptomatic COVID‐19 patients from uninfected controls with matched comorbidities and delineated those with moderate disease from those who were critically ill. Specifically, EN‐RAGE, followed by TF and IL‐18R1, showed the strongest correlation with disease severity and length of hospitalization. Importantly, EVs from COVID‐19 patients induced apoptosis of pulmonary microvascular endothelial cells in the order of disease severity. In conclusion, our findings support a role for EVs in the pathogenesis of COVID‐19 disease and underpin the development of EV‐based approaches to predicting disease severity, determining need for patient hospitalization and identifying new therapeutic targets.
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影响因子：
10.6
作者：
Bern MM
通讯作者：
Bern MM
DOI：
10.1056/nejmoa2022926
发表时间：
2020-11-19
期刊：
The New England journal of medicine
影响因子：
--
作者：
RECOVERY Collaborative Group;Horby P;Mafham M;Linsell L;Bell JL;Staplin N;Emberson JR;Wiselka M;Ustianowski A;Elmahi E;Prudon B;Whitehouse T;Felton T;Williams J;Faccenda J;Underwood J;Baillie JK;Chappell LC;Faust SN;Jaki T;Jeffery K;Lim WS;Montgomery A;Rowan K;Tarning J;Watson JA;White NJ;Juszczak E;Haynes R;Landray MJ
通讯作者：
Landray MJ
影响因子：
7.4
作者：
Giloteaux L;O'Neal A;Castro-Marrero J;Levine SM;Hanson MR
通讯作者：
Hanson MR
影响因子：
4.6
作者：
Brennan, K.;Martin, K.;Mc Gee, M. M.
通讯作者：
Mc Gee, M. M.
影响因子：
3.8
作者：
Bagheri, Vahid
通讯作者：
Bagheri, Vahid