SARS-CoV-2 infection of the oral cavity and saliva
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, David E. Kleiner, Michelly Sampaio De Melo, Esra Dikoglu, Sabina Desar, Kris Ylaya, Joon-Yong Chung, Grace Smith, Daniel S. Chertow, Kevin M. Vannella, Marcos Ramos-Benitez, Sabrina C. Ramelli, Shelly J. Samet, Ashley L. Babyak, Luis Perez Valenica, Mary E. Richert, Nicole Hays, Madeleine Purcell, Shreya Singireddy, Jocelyn Wu, Jean Chung, Amy Borth, Kimberly Bowers, Anne Weichold, Douglas Tran, Ronson J. Madathil, Eric M. Krause, Daniel L. Herr, Joseph Rabin, Joseph A. Herrold, Ali Tabatabai, Eric Hochberg, Christopher Cornachione, Andrea R. Levine, Michael T. McCurdy, Kapil K. Saharia, Zack Chancer, Michael A. Mazzeffi, Justin E. Richards, James W. Eagan, Yashvir Sangwan, Inês Sequeira, Sarah A. Teichmann, Adam J. Kimple, Karen Frank, Janice Lee, Richard C. Boucher, Sarah A. Teichmann, Blake M. Warner, Kevin M. Byrd
Journal: Nature Medicine (2021)

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. Single-cell transcriptomics and protein expression analyses of salivary glands and gingiva, along with the detection of infectious virus and virus-specific antibodies in saliva from SARS-CoV-2-infected individuals, support a potential role for the oral cavity in COVID-19 pathogenesis.