Title

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

Authors

Ni Huang, Wellcome Sanger Institute
Paola Pérez, National Institute of Dental and Craniofacial Research (NIDCR)
Takafumi Kato, UNC School of Medicine
Yu Mikami, UNC School of Medicine
Kenichi Okuda, UNC School of Medicine
Rodney C. Gilmore, UNC School of Medicine
Cecilia Domínguez Conde, Wellcome Sanger Institute
Billel Gasmi, National Institute of Dental and Craniofacial Research (NIDCR)
Sydney Stein, NIH Clinical Center (CC)
Margaret Beach, National Institute of Dental and Craniofacial Research (NIDCR)
Eileen Pelayo, National Institute of Dental and Craniofacial Research (NIDCR)
Jose O. Maldonado, National Institute of Dental and Craniofacial Research (NIDCR)
Bernard A. Lafont, National Institute of Allergy and Infectious Diseases (NIAID)
Shyh Ing Jang, National Institute of Dental and Craniofacial Research (NIDCR)
Nadia Nasir, National Cancer Institute (NCI)
Ricardo J. Padilla, The University of North Carolina at Chapel Hill
Valerie A. Murrah, The University of North Carolina at Chapel Hill
Robert Maile, UNC School of Medicine
William Lovell, The University of North Carolina at Chapel Hill
Shannon M. Wallet, UNC School of Medicine
Natalie M. Bowman, The University of North Carolina at Chapel Hill
Suzanne L. Meinig, UNC School of Medicine
Matthew C. Wolfgang, UNC School of Medicine
Saibyasachi N. Choudhury, J. Craig Venter Institute
Mark Novotny, J. Craig Venter Institute
Brian D. Aevermann, J. Craig Venter Institute
Richard H. Scheuermann, J. Craig Venter Institute
Gabrielle Cannon, UNC School of Medicine
Carlton W. Anderson, UNC School of Medicine
Rhianna E. Lee, UNC School of Medicine
Julie T. Marchesan, The University of North Carolina at Chapel Hill
Mandy Bush, The University of North Carolina at Chapel Hill

Document Type

Journal Article

Publication Date

5-1-2021

Journal

Nature Medicine

Volume

27

Issue

5

DOI

10.1038/s41591-021-01296-8

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.

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