Dataset Information

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

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.

SUBMITTER: Huang N

PROVIDER: S-EPMC8240394 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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

Huang Ni N Pérez Paola P Kato Takafumi T Mikami Yu Y Okuda Kenichi K Gilmore Rodney C RC Conde Cecilia Domínguez CD Gasmi Billel B Stein Sydney S Beach Margaret M Pelayo Eileen E Maldonado Jose O JO Lafont Bernard A BA Jang Shyh-Ing SI Nasir Nadia N Padilla Ricardo J RJ Murrah Valerie A VA Maile Robert R Lovell William W Wallet Shannon M SM Bowman Natalie M NM Meinig Suzanne L SL Wolfgang Matthew C MC Choudhury Saibyasachi N SN Novotny Mark M Aevermann Brian D BD Scheuermann Richard H RH Cannon Gabrielle G Anderson Carlton W CW Lee Rhianna E RE Marchesan Julie T JT Bush Mandy M Freire Marcelo M Kimple Adam J AJ Herr Daniel L DL Rabin Joseph J Grazioli Alison A Das Sanchita S French Benjamin N BN Pranzatelli Thomas T Chiorini John A JA Kleiner David E DE Pittaluga Stefania S Hewitt Stephen M SM Burbelo Peter D PD Chertow Daniel D Frank Karen K Lee Janice J Boucher Richard C RC Teichmann Sarah A SA Warner Blake M BM Byrd Kevin M KM

Nature medicine 20210325 5

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 ...[more]

PMID: 33767405

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Project description:BackgroundSARS-CoV-2 transmission mainly occurs through exposure of the upper airway mucosa to infected secretions such as saliva, which are excreted by an infected person. Thus, oral mucosal immunity plays a central role in the prevention of and early defense against SARS-CoV-2 infection. Although virus-specific antibody response has been extensively investigated in blood samples of SARS-CoV-2-infected patients and vaccinees, local humoral immunity in the oral cavity and its relationship to systemic antibody levels needs to be further addressed.Material and methodsWe fine-tuned a virus neutralization assay (vNTA) to measure the neutralizing activity (NA) of plasma and saliva samples from 20 SARS-CoV-2-infected (SI), 40 SARS-CoV-2-vaccinated (SV), and 28 SARS-CoV-2-vaccinated subjects with a history of infection (SIV) using the "wild type" SARS-CoV-2 lineage B.1 (EU) and the Delta (B.1.617.2) strains. To validate the vNTA results, the presence of neutralizing antibodies (NAbs) to the spike receptor binding domain (RBD) was evaluated with an ELISA assay.ResultsNA to SARS-CoV-2 lineage B.1 (EU) was present in plasma samples from all the tested subjects, with higher titers in SIV compared to both SI and SV. Conversely, NA was detected in saliva samples from 10.3% SV, 45% SI, and 92.6% SIV, with significantly lower titers in SV compared to both SI and SIV. The detection of NAbs in saliva reflected its reduced NA in SV.DiscussionThe difference in NA of plasma vs. saliva was confirmed in a vNTA where the SARS-CoV-2 B.1 and Delta strains were tested head-to-head, which also revealed a reduced NA of both specimens compared to the B.1 variant.ConclusionsThe administration of SARS-CoV-2 vaccines was associated with limited virus NA in the oral cavity, as measured in saliva and in comparison to plasma. This difference was more evident in vaccinees without a history of SARS-CoV-2 infection, possibly highlighting the importance of local exposure at the site of virus acquisition to effectively prevent the infection and block its spread. Nevertheless, the presence of immune escape mutations as possibly represented by the SARS-CoV-2 Delta variant negatively affects both local and systemic efficacy of NA associated with vaccination.

Dataset Information

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

Publications

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

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