严重急性呼吸综合征冠状病毒 2 在 COVID-19 死亡患者肺部、气道和血管内皮中的复制和嗜性的证据：一项尸检病例系列研究。

Evidence of Severe Acute Respiratory Syndrome Coronavirus 2 Replication and Tropism in the Lungs, Airways, and Vascular Endothelium of Patients With Fatal Coronavirus Disease 2019: An Autopsy Case Series.

机构信息

Infectious Diseases Pathology Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Respiratory Viruses Branch, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

出版信息

J Infect Dis. 2021 Mar 3;223(5):752-764. doi: 10.1093/infdis/jiab039.

DOI:10.1093/infdis/jiab039

PMID:33502471

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7928839/

Abstract

BACKGROUND

The coronavirus disease 2019 (COVID-19) pandemic continues to produce substantial morbidity and mortality. To understand the reasons for the wide-spectrum complications and severe outcomes of COVID-19, we aimed to identify cellular targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) tropism and replication in various tissues.

METHODS

We evaluated RNA extracted from formalin-fixed, paraffin-embedded autopsy tissues from 64 case patients (age range, 1 month to 84 years; 21 COVID-19 confirmed, 43 suspected COVID-19) by SARS-CoV-2 reverse-transcription polymerase chain reaction (RT-PCR). For cellular localization of SARS-CoV-2 RNA and viral characterization, we performed in situ hybridization (ISH), subgenomic RNA RT-PCR, and whole-genome sequencing.

RESULTS

SARS-CoV-2 was identified by RT-PCR in 32 case patients (21 COVID-19 confirmed, 11 suspected). ISH was positive in 20 and subgenomic RNA RT-PCR was positive in 17 of 32 RT-PCR-positive case patients. SARS-CoV-2 RNA was localized by ISH in hyaline membranes, pneumocytes, and macrophages of lungs; epithelial cells of airways; and endothelial cells and vessel walls of brain stem, leptomeninges, lung, heart, liver, kidney, and pancreas. The D614G variant was detected in 9 RT-PCR-positive case patients.

CONCLUSIONS

We identified cellular targets of SARS-CoV-2 tropism and replication in the lungs and airways and demonstrated its direct infection in vascular endothelium. This work provides important insights into COVID-19 pathogenesis and mechanisms of severe outcomes.

摘要

背景

2019 年冠状病毒病（COVID-19）大流行仍在导致大量发病和死亡。为了了解 COVID-19 出现广泛并发症和严重结局的原因，我们旨在确定严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在各种组织中的细胞靶标和复制。

方法

我们通过 SARS-CoV-2 逆转录聚合酶链反应（RT-PCR）评估了来自 64 例尸检组织的福尔马林固定、石蜡包埋的 RNA（年龄范围为 1 个月至 84 岁；21 例 COVID-19 确诊，43 例疑似 COVID-19）。为了进行 SARS-CoV-2 RNA 的细胞定位和病毒特征分析，我们进行了原位杂交（ISH）、亚基因组 RNA RT-PCR 和全基因组测序。

结果

RT-PCR 在 32 例病例患者中鉴定出 SARS-CoV-2（21 例 COVID-19 确诊，11 例疑似）。ISH 阳性 20 例，亚基因组 RNA RT-PCR 阳性 17 例。ISH 阳性的 32 例 RT-PCR 阳性病例患者中，SARS-CoV-2 RNA 定位于肺的透明膜、肺泡和巨噬细胞；气道的上皮细胞；以及脑桥、软脑膜、肺、心脏、肝脏、肾脏和胰腺的血管内皮细胞和血管壁。在 9 例 RT-PCR 阳性病例患者中检测到 D614G 变体。