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

Abstract

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.

ILC1: guardians of the oral mucosa against enemy viruses

“…Several viruses, including poxviruses, papillomaviruses, herpesviruses, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; Huang et al., 2020 ), invade via and replicate in the oral epithelium. Thus, it is of medical importance to better understand tissue surveillance within the oral mucosa.…”

Coronavirus 2019 Infectious Disease Epidemic: Where We Are, What Can Be Done and Hope For

“…A very recent study revealed that SARS-CoV-2 multiplies robustly in the oral cavity, and this likely explains why patients with COVID-19 express a range of oral manifestations such as ageusia and oral blisters. 51 In summary, the following points are noted: (1) infectivity is higher immediately before and soon after the onset of symptoms; however infected patients can remain infectious for about 2 weeks; (2) ten days from the appearance of the initial symptoms, the risk that a patient is still infections varies between 1% to 10% at a 95% CI; (3) infectivity is related to the viral load, but not to the development and severity of COVID-19; (4) individuals with a low viral load, determined by Ct greater than or equal to 35, may be infectious; (5) the window of infectivity varies in different individuals and some may be infectious for several weeks (these "long-term spreaders" represent a fraction of the infected population, probably too small to significantly affect the spreading of the virus; thus, the quarantine length could ignore them. At lower levels of virus circulation, however, long-term spreaders may frustrate efforts to further curb the epidemic if the quarantine length is not long enough to account for their prolonged infectivity window); and (6) most importantly, asymptomatic individuals-who account for about 70% of infectionsseem able to spread the virus as well as those who become ill 50 ; if this is true, it will be much more difficult to contain the further spread of this pandemic.…”

COVID-19 and Dentistry in 72 Questions: An Overview of the Literature

“…The transmembrane protein receptor ACE2 (angiotensin 2 converting enzyme), as well as TMPRSS2 (transmembrane serine 2 protease) and furin enzymes, have been identified as critical determinants of oral SARS infectivity [ 189 ]. ACE2 is expressed on different cells of oral tissues including oral mucosa, gingiva, tongue, salivary glands, and tonsils [ 49 , 190 , 191 , 192 , 193 , 194 , 195 , 196 ] ( Figure 1 ). Almost 96% of ACE2-positive oral cells would locate in dorsal tongue.…”

“…The presence of ACE2 is confirmed in the taste epithelial cells of tongue fungiform papillae. The epithelial cells of salivary ducts and serous cells of human submandibular glands express abundantly ACE2 [ 191 , 195 , 196 ]. Its expression in epithelial cells of minor salivary glands is even higher than in lung cells, and could constitute a reservoir zone for SARS-CoV-2 in asymptomatic patients [ 193 , 196 ].…”