Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression.
Tissue-based SARS-CoV-2 detection in fatal COVID-19 infections: Sustained direct viral-induced damage is not necessary to drive disease progression.
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DOI：
10.1016/j.humpath.2021.04.012
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发表时间：
2021-08
期刊：
影响因子：
3.3
通讯作者：
Westra WH
中科院分区：
文献类型：
--
作者：
El Jamal SM;Pujadas E;Ramos I;Bryce C;Grimes ZM;Amanat F;Tsankova NM;Mussa Z;Olson S;Salem F;Miorin L;Aydillo T;Schotsaert M;Albrecht RA;Liu WC;Marjanovic N;Francoeur N;Sebra R;Sealfon SC;García-Sastre A;Fowkes M;Cordon-Cardo C;Westra WH
2019年冠状病毒病(新冠肺炎)是由严重急性呼吸综合征冠状病毒2号(SARS-CoV-2)引起的持续大流行。虽然已知病毒感染会触发炎症过程，导致组织损伤和器官衰竭，但尚不清楚是否需要直接的病毒损伤来维持细胞损伤。由于缺乏可视化SARS-CoV-2在受损组织中的存在和分布的优化方法，对致病机制的理解一直受到阻碍。我们首先建立了一个阳性对照细胞系(Vero E6)来验证SARS-CoV-2检测方法的有效性。然后，我们对14例新冠肺炎尸检病例的多个器官(肺、肾、心、肝、脑、肠、淋巴结和脾)进行了评估，使用免疫组织化学(IHC)和核蛋白蛋白以及RNA原位杂交(RNAISH)来检测Spike蛋白mRNA。组织检测方法与基于定量聚合酶链式反应(QPCR)的检测方法进行比较。在Vero E6阳性细胞系对照组中，14个肺组织中有1个(7%)检测到SARS-CoV-2，其他59个器官中均未检测到SARS-CoV-2。IHC结果与RNAISH结果完全一致。定量聚合酶链式反应证实SARS-CoV-2ISH阳性肺组织中病毒载量较高，而所有ISH阴性组织中病毒载量均为零或低。在死于新冠肺炎相关器官衰竭的患者中，使用基于组织的检测方法在很大程度上无法检测到SARS-CoV-2。即使在表现出广泛损伤的肺部，也只在一小部分病例中检测到SARS-CoV-2病毒RNA或蛋白质。这一观察结果支持病毒感染主要是多器官致病性促炎反应的触发因素这一概念。直接病毒组织损伤是一种短暂的现象，通常不会在疾病发展过程中持续下去。
Coronavirus disease 2019 (COVID-19) is an ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although viral infection is known to trigger inflammatory processes contributing to tissue injury and organ failure, it is unclear whether direct viral damage is needed to sustain cellular injury. An understanding of pathogenic mechanisms has been handicapped by the absence of optimized methods to visualize the presence and distribution of SARS-CoV-2 in damaged tissues. We first developed a positive control cell line (Vero E6) to validate SARS-CoV-2 detection assays. We then evaluated multiple organs (lungs, kidneys, heart, liver, brain, intestines, lymph nodes, and spleen) from fourteen COVID-19 autopsy cases using immunohistochemistry (IHC) for the spike and the nucleoprotein proteins, and RNA in situ hybridization (RNA ISH) for the spike protein mRNA. Tissue detection assays were compared with quantitative polymerase chain reaction (qPCR)-based detection. SARS-CoV-2 was histologically detected in the Vero E6 positive cell line control, 1 of 14 (7%) lungs, and none (0%) of the other 59 organs. There was perfect concordance between the IHC and RNA ISH results. qPCR confirmed high viral load in the SARS-CoV-2 ISH-positive lung tissue, and absent or low viral load in all ISH-negative tissues. In patients who die of COVID-19-related organ failure, SARS-CoV-2 is largely not detectable using tissue-based assays. Even in lungs showing widespread injury, SARS-CoV-2 viral RNA or proteins were detected in only a small minority of cases. This observation supports the concept that viral infection is primarily a trigger for multiple-organ pathogenic proinflammatory responses. Direct viral tissue damage is a transient phenomenon that is generally not sustained throughout disease progression.
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DOI：
10.1038/nrmicro1890
发表时间：
2008-05
期刊：
Nature reviews. Microbiology
影响因子：
--
作者：
Miller S;Krijnse-Locker J
通讯作者：
Krijnse-Locker J
影响因子：
50.3
作者：
Cordon-Cardo C;Pujadas E;Wajnberg A;Sebra R;Patel G;Firpo-Betancourt A;Fowkes M;Sordillo E;Paniz-Mondolfi A;Gregory J;Krammer F;Simon V;Isola L;Soon-Shiong P;Aberg JA;Fuster V;Reich DL
通讯作者：
Reich DL
影响因子：
15.8
作者：
Nicholls, JM;Butany, J;Wong, M
通讯作者：
Wong, M
影响因子：
3.9
作者：
Etievant, Sibyle;Bal, Antonin;Gaymard, Alexandre
通讯作者：
Gaymard, Alexandre
影响因子：
82.9
作者：
Amanat F;Stadlbauer D;Strohmeier S;Nguyen THO;Chromikova V;McMahon M;Jiang K;Arunkumar GA;Jurczyszak D;Polanco J;Bermudez-Gonzalez M;Kleiner G;Aydillo T;Miorin L;Fierer DS;Lugo LA;Kojic EM;Stoever J;Liu STH;Cunningham-Rundles C;Felgner PL;Moran T;García-Sastre A;Caplivski D;Cheng AC;Kedzierska K;Vapalahti O;Hepojoki JM;Simon V;Krammer F
通讯作者：
Krammer F