SARS-CoV-2 Infection of the Oral Cavity and Saliva

 


TAKE-HOME MESSAGE

  • Utilizing RNA sequencing and expression assessments, the authors of this study demonstrated that SARS-CoV-2 can infect and replicate within the glands and mucosa of the human oral cavity. Additionally, the authors found that saliva can serve as a vector for transmission of the virus in asymptomatic patients, and salivary viral load correlated with the degree of symptoms, namely loss of taste.
  • Prior to this study, it was unknown if SARS-CoV-2 could infect and replicate in the oral cavity. In addition to implicating the oral cavity as a potential source for transmission, this study indicates the need for additional evaluation of the interplay between the nasal and oral cavities in SARS-CoV-2 pathogenesis.
–  Laurie C. Carter, DDS, PhD

 Clinical Dentistry

The SARS-Cov-2 virus, which has gripped the world in a global pandemic, infects individuals and can result in myriad clinical presentations, including oral symptoms, suggesting that the virus might infect cells of the oral cavity. The angiotensin-converting enzyme 2 (ACE2) receptor and the transmembrane serine protease 2 (TMPRSS2) enzyme are thought to be the functional entry points/receptors for the COVID-19 virus.1 Earlier studies showed that oral tissues express the ACE2 receptor.2 The present study extends those findings. This study used single-cell RNA sequencing datasets of the human minor salivary glands and gingiva to examine the role of the oral cavity in SARS-CoV-2 infection and found evidence that the virus does infect epithelial cells in the oral cavity (mucosa and salivary glands), which could explain why some patients with COVID-19 present with oral manifestations, including loss of taste, dry mouth, and oral blistering.3,4

The research team also found that saliva could be infectious, indicating that the mouth may be an incubator for the SARS-CoV-2 virus and is important in transmitting the virus. In this study, saliva from people with asymptomatic COVID-19 was exposed to healthy cells in vitro; saliva from 2 of 8 subjects caused healthy cells to become infected, showing that it may be possible for asymptomatic people to transmit the virus to others through saliva. Asymptomatic spread of the COVID-19 infection has been a significant problem in this pandemic. Interestingly, the authors also identified that the nasopharyngeal swab and saliva exhibited distinct viral shedding properties and dynamics within the same patients; yet again, demonstrating the uniqueness of the oral microenvironment. The study also found that the levels of SARS-CoV-2 in saliva correlated with taste alterations, suggesting that oral infection could be the reason for oral symptoms. Further, saliva, when swallowed or aspirated, may also transmit SARS-CoV-2 into the lungs or other organ sites and potentially seed other sites of infection.

These important findings lay foundational new knowledge that helps us begin to understand why there are persistent oral symptoms in some individuals. These findings also support the development of potential new strategies focused on the oral cavity to prevent COVID-19 transmission and for treatment of the disease.

Representative Clinical Photographs


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Source: Corchuelo et al (2020).5

References

  1. Hoffmann M, Kleine-Weber H, Schroeder S, et al. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181(2):271-280.e8. https://linkinghub.elsevier.com/retrieve/pii/S0092-8674(20)30229-4
  2. Xu H, Zhong L, Deng J, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):8. https://www.nature.com/articles/s41368-020-0074-x
  3. Huang N, Pérez P, Kato T, et al. SARS-CoV-2 infection of the oral cavity and saliva Nat Med. 2021 Mar 25. DOI:10.1038/s41591-021-01296-8. Online ahead of print. https://www.nature.com/articles/s41591-021-01296-8
  4. Xydakis MS, Dehgani-Mobaraki P, Holbrook EH, et al. Smell and taste dysfunction in patients with COVID-19. Lancet Infect Dis. 2020;20(9):1015-1016. https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30293-0/fulltext
  5. Corchuelo J, Ulloa FC. Oral manifestations in a patient with a history of asymptomatic COVID-19: case report. Int J Infect Dis. 2020;100:154-157. https://www.ijidonline.com/article/S1201-9712(20)30700-1/fulltext

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.

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