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

Byrd, K. M.; Huang, N.; Perez, P.; Kato, T.; Mikami, Y.; Okuda, K.; Gilmore, R. C.; Conde, C. D.; Gasmi, B.; Stein, S.; Beach, M.; Pelayo, E.; Maldonado-Ortiz, J.; LaFont, B.; Padilla, R.; Murrah, V.; Maile, R.; Lovell, W.; Wallet, S.; Bowman, N. M.; Meinig, S. L.; Wolfgang, M. C.; Choudhury, S. N.; Novotny, M.; Aevermann, B. D.; Scheuermann, R.; Cannon, G.; Anderson, C.; Marchesan, J.; Bush, M.; Freire, M.; Kimple, A.; Herr, D. L.; Rabin, J.; Grazioli, A.; French, B. N.; Pranzatelli, T. J.; Chiorini, J. A.; Kleiner, D. E.; Pittaluga, S.; Hewitt, S.; Burbelo, P. D.; Chertow, D.; NIHCOVID-19, A

Despite signs of infection, the involvement of the oral cavity in COVID-19 is poorly understood. To address this, single-cell RNA sequencing datasets 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 andimplicates saliva in viral transmission.