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

Ni Huang(Wellcome Sanger Institute), Paola Pérez(National Institutes of Health), Takafumi Kato(University of North Carolina at Chapel Hill), Yu Mikami(University of North Carolina at Chapel Hill), Kenichi Okuda(University of North Carolina at Chapel Hill), Rodney C. Gilmore(University of North Carolina at Chapel Hill), Cecilia Domínguez Conde(Wellcome Sanger Institute), Billel Gasmi(National Institutes of Health), Sydney Stein(National Institutes of Health Clinical Center), Margaret Beach(National Institutes of Health), Eileen Pelayo(National Institutes of Health), José O. Maldonado(National Institutes of Health), Bernard A. P. Lafont(National Institutes of Health), Shyh-Ing Jang(National Institutes of Health), Nadia Nasir(National Institutes of Health), Ricardo J. Padilla(University of North Carolina at Chapel Hill), Valerie A. Murrah(University of North Carolina at Chapel Hill), Robert Maile(University of North Carolina at Chapel Hill), William Lovell(University of North Carolina at Chapel Hill), Shannon M. Wallet(University of North Carolina at Chapel Hill), Natalie M. Bowman(University of North Carolina at Chapel Hill), Suzanne L. Meinig(University of North Carolina at Chapel Hill), Matthew C. Wolfgang(University of North Carolina at Chapel Hill), 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(University of North Carolina at Chapel Hill), Carlton W. Anderson(University of North Carolina at Chapel Hill), Rhianna E. Lee(University of North Carolina at Chapel Hill), Julie T. Marchesan(University of North Carolina at Chapel Hill), Mandy Bush(University of North Carolina at Chapel Hill), Marcelo Freire(J. Craig Venter Institute), Adam J. Kimple(University of North Carolina at Chapel Hill), Daniel Herr(University of Maryland, Baltimore), Joseph Rabin(University of Maryland, Baltimore), Alison Grazioli(National Institutes of Health), Sanchita Das(National Institutes of Health Clinical Center), Benjamin French(National Institutes of Health), Thomas Pranzatelli(National Institutes of Health), John A. Chiorini(National Institutes of Health), David E. Kleiner(National Institutes of Health), Stefania Pittaluga(National Institutes of Health), Stephen M. Hewitt(National Institutes of Health), Peter D. Burbelo(National Institutes of Health), Daniel S. Chertow(National Institutes of Health Clinical Center), David E. Kleiner(National Institutes of Health), Michelly Sampaio De Melo(National Institutes of Health), Esra Dikoglu(National Institutes of Health), Sabina Desar(National Institutes of Health), Kris Ylaya(National Institutes of Health), Joon‐Yong Chung(University of Maryland, Baltimore), Grace Smith(National Institutes of Health), Daniel S. Chertow(National Institutes of Health Clinical Center), Kevin M. Vannella(National Institutes of Health Clinical Center), Marcos J. Ramos-Benítez(National Institutes of Health Clinical Center), Sabrina Ramelli(National Institutes of Health Clinical Center), Shelly Samet(National Institutes of Health Clinical Center), Ashley L. Babyak(National Institutes of Health Clinical Center), Luis Perez Valencia(National Institutes of Health Clinical Center), Mary Richert(National Institutes of Health Clinical Center), Nicole Hays(University of Maryland, Baltimore), Madeleine Purcell(University of Maryland, Baltimore), Shreya Singireddy(University of Maryland, Baltimore), Jocelyn Wu(University of Maryland, Baltimore), Jean Chung(University of Maryland, Baltimore), Amy Borth(University of Maryland, Baltimore), Kimberly Bowers(University of Maryland, Baltimore), Anne Weichold(University of Maryland, Baltimore), Douglas Tran(University of Maryland, Baltimore), Ronson J. Madathil(University of Maryland, Baltimore), Eric Krause(University of Maryland, Baltimore), Daniel Herr(University of Maryland, Baltimore), Joseph Rabin(University of Maryland, Baltimore), Joseph A. Herrold(University of Maryland, Baltimore), Ali Tabatabai(University of Maryland, Baltimore), Eric Hochberg(University of Maryland, Baltimore), Christopher R. Cornachione(University of Maryland, Baltimore), Andrea R. Levine(University of Maryland, Baltimore), Michael T. McCurdy(University of Maryland, Baltimore), Kapil Saharia(University of Maryland, Baltimore), Zack Chancer(University of Maryland, Baltimore), Michael Mazzeffi(University of Maryland, Baltimore), Justin E. Richards(University of Maryland, Baltimore), James W. Eagan(St. Joseph Medical Center), Yashvir Sangwan(Peninsula Regional Medical Center), HCA Oral and Craniofacial Biological Network(Queen Mary University of London), Inês Sequeira(Queen Mary University of London), Sarah A. Teichmann(University of North Carolina at Chapel Hill), Adam J. Kimple(University of North Carolina at Chapel Hill), Karen M. Frank(National Institutes of Health), Janice S. Lee(University of North Carolina at Chapel Hill), Richard C. Boucher(University of North Carolina at Chapel Hill), Sarah A. Teichmann(National Institutes of Health), Blake M. Warner(National Institute of Dental and Craniofacial Research), Kevin M. Byrd(University of North Carolina at Chapel Hill)
Nature Medicine
March 25, 2021
10.1038/s41591-021-01296-8
Cited by 816Open Access
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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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