Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis

Ni Huang(University of North Carolina at Chapel Hill), 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(University of North Carolina at Chapel Hill), Billel Gasmi(National Institutes of Health), Sydney Stein(National Institute of Dental and Craniofacial Research), Margaret Beach(National Institutes of Health), Eileen Pelayo(National Institutes of Health), José O. Maldonado(National Institutes of Health), Bernard A. P. Lafont(Bridge University), Ricardo 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), W. George 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 Anderson(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), Benjamin N. 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 Institute of Dental and Craniofacial Research), HCA Oral and Craniofacial Biological Network(National Institutes of Health Clinical Center), Karen M. Frank(National Institutes of Health), Janice 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(University of North Carolina at Chapel Hill), Kevin M. Byrd
medRxiv
October 27, 2020
10.1101/2020.10.26.20219089
Cited by 48Open Access
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Abstract

ABSTRACT Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing data-sets were integrated from human minor salivary glands and gingiva to identify 11 epithelial, 7 mesenchymal, and 15 immune cell clusters. Analysis of SARS-CoV-2 viral entry factor expression showed enrichment in epithelia including the ducts and acini of the salivary glands and the suprabasal cells of the mucosae. COVID-19 autopsy tissues confirmed in vivo SARS-CoV-2 infection in the salivary glands and mucosa. Saliva from SARS-CoV-2-infected individuals harbored epithelial cells exhibiting ACE2 expression and SARS-CoV-2 RNA. Matched nasopharyngeal and saliva samples found distinct viral shedding dynamics and viral burden in saliva correlated with COVID-19 symptoms including taste loss. Upon recovery, this cohort exhibited salivary antibodies against SARS-CoV-2 proteins. Collectively, the oral cavity represents a robust site for COVID-19 infection and implicates saliva in viral transmission.

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