• ACE2和TMPRSS广泛富集于唾液腺和口腔黏膜的上皮细胞;
  • 在18名新冠肺炎死亡患者的尸检中,16/28的唾液腺及5/6的口腔黏膜样本可检测到新冠病毒;
  • 口腔黏膜上皮细胞(pCK+)可能是新冠病毒首先感染的细胞亚群,并脱落至唾液中;
  • 无症状感染者的唾液中非细胞和细胞组分可在体外传播新冠病毒,恢复后其唾液中持续存在抗新冠病毒IgG抗体;
  • 同一患者的鼻咽和唾液样本显示出不同的病毒脱落动力学,唾液病毒载量与味觉减退等COVID-19症状相关。
尽管新冠病毒感染可导致味觉减退、口干及口腔黏膜损伤,但口腔是否参与新冠病毒的感染关联尚未明确。Nature Medicine上发表的一项最新研究,发现口腔粘膜及唾液中的上皮细胞可表达新冠病毒进入因子——如ACE2及TMPRSS,提示口腔是新冠病毒感染的重要部位,而唾液是新冠病毒传播的潜在途径。本结果对于新冠肺炎检测、感染机制研究都具有参考价值。
Nature Medicine [IF:36.13]

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



03-25, Article

Abstract & Authors:展开

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.

First Authors:
Ni Huang,Paola Pérez,Takafumi Kato,Yu Mikami

Correspondence Authors:
Blake M Warner,Kevin M Byrd

All Authors:
Ni Huang,Paola Pérez,Takafumi Kato,Yu Mikami,Kenichi Okuda,Rodney C Gilmore,Cecilia Domínguez Conde,Billel Gasmi,Sydney Stein,Margaret Beach,Eileen Pelayo,Jose O Maldonado,Bernard A Lafont,Shyh-Ing Jang,Nadia Nasir,Ricardo J Padilla,Valerie A Murrah,Robert Maile,William Lovell,Shannon M Wallet,Natalie M Bowman,Suzanne L Meinig,Matthew C Wolfgang,Saibyasachi N Choudhury,Mark Novotny,Brian D Aevermann,Richard H Scheuermann,Gabrielle Cannon,Carlton W Anderson,Rhianna E Lee,Julie T Marchesan,Mandy Bush,Marcelo Freire,Adam J Kimple,Daniel L Herr,Joseph Rabin,Alison Grazioli,Sanchita Das,Benjamin N French,Thomas Pranzatelli,John A Chiorini,David E Kleiner,Stefania Pittaluga,Stephen M Hewitt,Peter D Burbelo,Daniel Chertow,NIH COVID- Autopsy Consortium,HCA Oral and Craniofacial Biological Network,Karen Frank,Janice Lee,Richard C Boucher,Sarah A Teichmann,Blake M Warner,Kevin M Byrd