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SARS-CoV-2 对口腔和唾液的感染。

SARS-CoV-2 infection of the oral cavity and saliva.

机构信息

Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Salivary Disorders Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.

出版信息

Nat Med. 2021 May;27(5):892-903. doi: 10.1038/s41591-021-01296-8. Epub 2021 Mar 25.

Abstract

Despite signs of infection-including taste loss, dry mouth and mucosal lesions such as ulcerations, enanthema and macules-the involvement of the oral cavity in coronavirus disease 2019 (COVID-19) is poorly understood. To address this, we generated and analyzed two single-cell RNA sequencing datasets of the human minor salivary glands and gingiva (9 samples, 13,824 cells), identifying 50 cell clusters. Using integrated cell normalization and annotation, we classified 34 unique cell subpopulations between glands and gingiva. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral entry factors such as ACE2 and TMPRSS members were broadly enriched in epithelial cells of the glands and oral mucosae. Using orthogonal RNA and protein expression assessments, we confirmed SARS-CoV-2 infection in the glands and mucosae. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 and TMPRSS expression and sustained SARS-CoV-2 infection. Acellular and cellular salivary fractions from asymptomatic individuals were found to transmit SARS-CoV-2 ex vivo. Matched nasopharyngeal and saliva samples displayed distinct viral shedding dynamics, and salivary viral burden correlated with COVID-19 symptoms, including taste loss. Upon recovery, this asymptomatic cohort exhibited sustained salivary IgG antibodies against SARS-CoV-2. Collectively, these data show that the oral cavity is an important site for SARS-CoV-2 infection and implicate saliva as a potential route of SARS-CoV-2 transmission.

摘要

尽管有感染迹象,包括味觉丧失、口干和黏膜病变,如溃疡、口炎和斑疹,但人们对 2019 年冠状病毒病(COVID-19)口腔受累的认识仍很有限。为了解决这个问题,我们生成并分析了人类小唾液腺和牙龈的两个单细胞 RNA 测序数据集(9 个样本,13824 个细胞),确定了 50 个细胞簇。通过整合细胞归一化和注释,我们对腺体和牙龈之间的 34 个独特细胞亚群进行了分类。严重急性呼吸综合征冠状病毒 2(SARS-CoV-2)病毒进入因子,如 ACE2 和 TMPRSS 成员,在腺体和口腔黏膜的上皮细胞中广泛富集。通过正交 RNA 和蛋白质表达评估,我们证实了 SARS-CoV-2 在腺体和黏膜中的感染。从 SARS-CoV-2 感染个体的唾液中分离出的上皮细胞表现出 ACE2 和 TMPRSS 的表达,并持续感染 SARS-CoV-2。从无症状个体中分离出的无细胞和细胞唾液部分被发现可在体外传播 SARS-CoV-2。配对的鼻咽和唾液样本显示出不同的病毒脱落动力学,唾液中的病毒负担与 COVID-19 症状相关,包括味觉丧失。在康复后,这个无症状队列对 SARS-CoV-2 表现出持续的唾液 IgG 抗体。总的来说,这些数据表明口腔是 SARS-CoV-2 感染的重要部位,并提示唾液可能是 SARS-CoV-2 传播的潜在途径。

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