The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling.
The fatal trajectory of pulmonary COVID-19 is driven by lobular ischemia and fibrotic remodelling.
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DOI：
10.1016/j.ebiom.2022.104296
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发表时间：
2022-11
期刊：
影响因子：
11.1
通讯作者：
Caruso, Arnaldo
中科院分区：
文献类型：
--
作者：
Caccuri, Francesca;Caruso, Arnaldo
COVID-19的特点是临床表现多样，从轻微症状到严重病程不等。9-20%的严重肺部疾病住院患者死于COVID-19，大量幸存者发展为长期COVID。我们的目标是全面了解严重COVID-19的病理生理学，并确定疾病严重程度和治疗反应的液体生物标志物。我们总共研究了85个肺（n = 31份COVID尸检样本; n = 7份甲型流感尸检样本; n = 18份间质性肺病外植体; n = 24名健康对照）使用最高分辨率的基于同步辐射的分层相衬断层扫描、微血管腐蚀铸型的扫描电子显微镜、免疫组织化学、基质辅助激光解吸电离质谱成像，以及mRNA表达和生物学途径的分析。使用ELISA将来自所有疾病组的血浆样品用于液体生物标志物测定。解剖/分子数据作为患者住院时间的函数进行分析。在常规肺成像中观察到的COVID-19斑片状/马赛克状外观是由微血管闭塞和继发性小叶缺血引起的。住院时间的长短与炎症性血管生成的增加有关。这与增强的血管生成和纤维化基因表达相关，分子谱和代谢组学分析证实了这一点。血浆纤维化标志物增加与肺组织转录水平相关，并预测疾病严重程度。血浆分析证实了不同的纤维化生物标志物（TSP 2，GDF 15，IGFBP 7，Pro-C3），这些生物标志物预测了COVID-19的致命轨迹。肺部重度COVID-19是继发性小叶微缺血和纤维化重塑的结果，导致独特形式的纤维化间质性肺病，导致长期COVID。这个项目是由一些资助者促成的。完整的列表可以在手稿末尾的利益声明/致谢部分找到。
COVID-19 is characterized by a heterogeneous clinical presentation, ranging from mild symptoms to severe courses of disease. 9–20% of hospitalized patients with severe lung disease die from COVID-19 and a substantial number of survivors develop long-COVID. Our objective was to provide comprehensive insights into the pathophysiology of severe COVID-19 and to identify liquid biomarkers for disease severity and therapy response. We studied a total of 85 lungs (n = 31 COVID autopsy samples; n = 7 influenza A autopsy samples; n = 18 interstitial lung disease explants; n = 24 healthy controls) using the highest resolution Synchrotron radiation-based hierarchical phase-contrast tomography, scanning electron microscopy of microvascular corrosion casts, immunohistochemistry, matrix-assisted laser desorption ionization mass spectrometry imaging, and analysis of mRNA expression and biological pathways. Plasma samples from all disease groups were used for liquid biomarker determination using ELISA. The anatomic/molecular data were analyzed as a function of patients’ hospitalization time. The observed patchy/mosaic appearance of COVID-19 in conventional lung imaging resulted from microvascular occlusion and secondary lobular ischemia. The length of hospitalization was associated with increased intussusceptive angiogenesis. This was associated with enhanced angiogenic, and fibrotic gene expression demonstrated by molecular profiling and metabolomic analysis. Increased plasma fibrosis markers correlated with their pulmonary tissue transcript levels and predicted disease severity. Plasma analysis confirmed distinct fibrosis biomarkers (TSP2, GDF15, IGFBP7, Pro-C3) that predicted the fatal trajectory in COVID-19. Pulmonary severe COVID-19 is a consequence of secondary lobular microischemia and fibrotic remodelling, resulting in a distinctive form of fibrotic interstitial lung disease that contributes to long-COVID. This project was made possible by a number of funders. The full list can be found within the Declaration of interests / Acknowledgements section at the end of the manuscript.
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影响因子：
64.5
作者：
Aid M;Busman-Sahay K;Vidal SJ;Maliga Z;Bondoc S;Starke C;Terry M;Jacobson CA;Wrijil L;Ducat S;Brook OR;Miller AD;Porto M;Pellegrini KL;Pino M;Hoang TN;Chandrashekar A;Patel S;Stephenson K;Bosinger SE;Andersen H;Lewis MG;Hecht JL;Sorger PK;Martinot AJ;Estes JD;Barouch DH
通讯作者：
Barouch DH
影响因子：
158.5
作者：
Ackermann, Maximilian;Verleden, Stijn E.;Jonigk, Danny
通讯作者：
Jonigk, Danny
Covid-19中的静脉和动脉血栓形成：更新的叙述性评论。
影响因子：
6.7
作者：
Al Duhailib, Zainab;Oczkowski, Simon;Polok, Kamil;Fronczek, Jakub;Szczeklik, Wojciech;Piticaru, Joshua;Mammen, Manoj J.;Alshamsi, Fayez;Eikelboom, John;Belley-Cote, Emilie;Alhazzani, Waleed
通讯作者：
Alhazzani, Waleed
影响因子：
4.5
作者：
Caccuri F;Bugatti A;Zani A;De Palma A;Di Silvestre D;Manocha E;Filippini F;Messali S;Chiodelli P;Campisi G;Fiorentini S;Facchetti F;Mauri P;Caruso A
通讯作者：
Caruso A
DOI：
10.1172/jci161167
发表时间：
2022-08-01
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Ahamed J;Laurence J
通讯作者：
Laurence J