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在 COVID-19 患者的肺部和呼吸道中原位检测 SARS-CoV-2。

In situ detection of SARS-CoV-2 in lungs and airways of patients with COVID-19.

机构信息

Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.

Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, USA.

出版信息

Mod Pathol. 2020 Nov;33(11):2104-2114. doi: 10.1038/s41379-020-0595-z. Epub 2020 Jun 19.

Abstract

Coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has led to a global public health crisis. In elderly individuals and those with comorbidities, COVID-19 is associated with high mortality, frequently caused by acute respiratory distress syndrome. We examine in situ expression of SARS-CoV-2 in airways and lung obtained at autopsy of individuals with confirmed COVID-19 infection. Seven autopsy cases (male, N = 5; female, N = 2) with reverse transcriptase-polymerase chain reaction (RT-PCR)-confirmed SARS-CoV-2 infection and a median age of 66 years (range, 50-77 years) were evaluated using a rabbit polyclonal antibody against SARS Nucleocapsid protein in correlation with clinical parameters. The median time from symptom onset to death was 9 days (range, 6-31 days), from hospitalization 7 days (range, 1-21 days), from positive RT-PCR 7 days (range, 0-18 days), and from intensive care unit admission defining onset of respiratory failure 3 days (range, 1-18 days). Chest imaging identified diffuse airspace disease in all patients corresponding to acute and (N = 5) or organizing (N = 2) diffuse alveolar damage (DAD) on histologic examination. Among five patients with acute-phase DAD (≤7 days from onset of respiratory failure), SARS-CoV-2 was detected in pulmonary pneumocytes and ciliated airway cells (N = 5), and in upper airway epithelium (N = 2). In two patients with organizing DAD (>14 days from onset of respiratory failure), no virus was detected in lungs or airways. No endothelial cell infection was observed. The findings suggest that SARS-CoV-2 infection of epithelial cells in lungs and airways of patients with COVID-19 who developed respiratory failure can be detected during the acute phase of lung injury and is absent in the organizing phase.

摘要

由严重急性呼吸综合征冠状病毒 2 型(SARS-CoV-2)引起的 2019 年冠状病毒病(COVID-19)导致了一场全球公共卫生危机。在老年人和合并症患者中,COVID-19 与高死亡率相关,通常由急性呼吸窘迫综合征引起。我们检查了经逆转录酶-聚合酶链反应(RT-PCR)确诊的 COVID-19 感染患者尸检中呼吸道和肺部的 SARS-CoV-2 原位表达。使用针对 SARS 核衣壳蛋白的兔多克隆抗体,对 7 例经 RT-PCR 确诊的 SARS-CoV-2 感染尸检病例(男性,N=5;女性,N=2)进行评估,这些病例的中位年龄为 66 岁(范围,50-77 岁),并与临床参数相关联。从症状出现到死亡的中位时间为 9 天(范围,6-31 天),从住院到死亡的中位时间为 7 天(范围,1-21 天),从 RT-PCR 阳性到死亡的中位时间为 7 天(范围,0-18 天),从入住重症监护病房定义呼吸衰竭开始的中位时间为 3 天(范围,1-18 天)。胸部影像学在所有患者中均识别出弥漫性气腔疾病,对应于组织学检查中的急性和(N=5)或机化性(N=2)弥漫性肺泡损伤(DAD)。在 5 例急性 DAD 患者(呼吸衰竭开始后≤7 天)中,SARS-CoV-2 检测到肺型上皮细胞和纤毛气道细胞(N=5)和上呼吸道上皮细胞(N=2)。在 2 例机化性 DAD 患者(呼吸衰竭开始后>14 天)中,肺部或气道中均未检测到病毒。未观察到内皮细胞感染。这些发现表明,在发生呼吸衰竭的 COVID-19 患者的肺部和气道上皮细胞中,可以在肺损伤的急性期检测到 SARS-CoV-2 感染,而在机化期则不存在。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c8/9813561/c98f3ed96f4f/gr1_lrg.jpg

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