Huang N, Pérez P, Kato T, Mikami Y, Okuda K, Gilmore RC, Conde CD, Gasmi B, Stein S, Beach M, Pelayo E, Maldonado JO, Lafont BA, Jang SI, Nasir N, Padilla RJ, Murrah VA, Maile R, Lovell W, Wallet SM, Bowman NM, Meinig SL, Wolfgang MC, Choudhury SN, Novotny M, Aevermann BD, Scheuermann RH, Cannon G, Anderson CW, Lee RE, Marchesan JT, Bush M, Freire M, Kimple AJ, Herr DL, Rabin J, Grazioli A, Das S, French BN, Pranzatelli T, Chiorini JA, Kleiner DE, Pittaluga S, Hewitt SM, Burbelo PD, Chertow D, NIH COVID-19 Autopsy Consortium, HCA Oral and Craniofacial Biological Network, Frank K, Lee J, Boucher RC, Teichmann SA, Warner BM, Byrd KM
SARS-CoV-2 infection of the oral cavity and saliva.
Nature medicine. 2021-03-25;
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.