Integrated Single-Cell Atlases Reveal an Oral SARS-CoV-2 Infection and Transmission Axis
Huang N, Perez P, Kato T, Mikami Y, Okuda K, Gilmore RC, Domínguez Conde C, Gasmi B, Stein S, Beach M, Pelayo E, Maldonado J, LaFont B, Padilla R, Murrah V, Maile R, Lovell W, Wallet S, Bowman NM, Meinig SL, Wolfgang MC, Choudhury SN, Novotny M, Aevermann BD, Scheuermann R, Cannon G, Anderson C, Marchesan J, Bush M, Freire M, Kimple A, Herr DL, Rabin J, Grazioli A, French BN, Pranzatelli T, Chiorini JA, Kleiner DE, Pittaluga S, Hewitt S, Burbelo PD, Chertow D, Frank K, Lee J, Boucher RC, Teichmann SA, Warner BM, Byrd KM
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 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.