Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2
Ultrastructural Evidence for Direct Renal Infection with SARS-CoV-2
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DOI：
10.1681/asn.2020040432
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发表时间：
2020-08-01
影响因子：
13.6
通讯作者：
Jentzen, Jeffrey M.
中科院分区：
文献类型：
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作者：
Farkash, Evan A.;Wilson, Allecia M.;Jentzen, Jeffrey M.
背景2019冠状病毒病（COVID-19）患者中有很大一部分显示肾功能异常。对中国武汉COVID-19住院患者的回顾性研究报告称，进展为ARF的发病率为3%-7%，这是预后不良的标志。COVID-19肾功能衰竭的原因尚不清楚，但有一种假设机制是由致病病毒SARS-CoV-2直接感染肾脏。方法我们对1例因COVID-19死亡的患者进行了尸检，该患者在开放式主动脉夹层修复术后死亡，并发缺氧性呼吸衰竭和少尿性肾功能衰竭。我们用光学和电子显微镜检查肾组织的证据SARS-CoV-2在肾cells.Results近端小管的光学显微镜下表现出地理等距空泡化，对应于一个重点的小管与丰富的细胞内病毒阵列。单个病毒的平均直径为76毫米，包膜上布满了冠状的电子密集刺突。结论肾小管上皮细胞中存在与SARS-CoV-2在形态上相同的病毒颗粒，并具有病毒阵列和病毒组装的其他特征，这为SARS-CoV-2直接感染肾脏提供了证据。这一发现提供了证实性证据，表明在COVID-19的阿基背景下发生直接肾脏感染。然而，COVID-19直接感染的频率和临床意义尚不清楚。光学显微镜下观察到的管状等长空泡化与电子显微镜下观察到的含有空泡的双膜囊泡相关，可能是肾活检或尸检标本中活动性SARS-CoV-2感染的有用组织学标志物。
Background A significant fraction of patients with coronavirus disease 2019 (COVID-19) display abnormalities in renal function. Retrospective studies of patients hospitalized with COVID-19 in Wuhan, China, report an incidence of 3%-7% progressing to ARF, a marker of poor prognosis. The cause of the renal failure in COVID-19 is unknown, but one hypothesized mechanism is direct renal infection by the causative virus, SARS-CoV-2.Methods We performed an autopsy on a single patient who died of COVID-19 after open repair of an aortic dissection, complicated by hypoxic respiratory failure and oliguric renal failure. We used light and electron microscopy to examine renal tissue for evidence of SARS-CoV-2 within renal cells.Results Light microscopy of proximal tubules showed geographic isometric vacuolization, corresponding to a focus of tubules with abundant intracellular viral arrays. Individual viruses averaged 76 mm in diameter and had an envelope studded with crown-like, electron-dense spikes. Vacuoles contained double-membrane vesicles suggestive of partially assembled virus.Conclusions The presence of viral particles in the renal tubular epithelium that were morphologically identical to SARS-CoV-2, and with viral arrays and other features of virus assembly, provide evidence of a productive direct infection of the kidney by SARS-CoV-2. This finding offers confirmatory evidence that direct renal infection occurs in the setting of AKI in COVID-19. However, the frequency and clinical significance of direct infection in COVID-19 is unclear. Tubular isometric vacuolization observed with light microscopy, which correlates with double-membrane vesicles containing vacuoles observed with electronic microscopy, may be a useful histologic marker for active SARS-CoV-2 infection in kidney biopsy or autopsy specimens.