Scientists find evidence that the new coronavirus infects cells in the mouth – saliva may play a role in the transmission of COVID

The findings financed by the NIH point to a role for saliva in SARS-CoV-2 streaming.

An international team of scientists has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects the cells of the mouth. Although it is well known that the upper respiratory tract and lungs are the primary sites of SARS-CoV-2 infection, there is evidence that the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and , as this new study shows, the mouth.

The virus’s potential to infect various areas of the body can help explain the various symptoms experienced by patients with COVID-19, including oral symptoms such as loss of taste, dry mouth and blisters. In addition, the findings point to the possibility that the mouth plays a role in the transmission of SARS-CoV-2 to the lungs or digestive system through saliva loaded with virus from infected oral cells. A better understanding of the involvement of the mouth can inform strategies to reduce viral transmission inside and outside the body. The team was led by researchers from the National Institutes of Health and the University of North Carolina at Chapel Hill.

“Due to the NIH’s direct response to the pandemic, researchers at the National Institute for Dental and Craniofacial Research were able to quickly apply their knowledge in oral biology and medicine to answer key questions about COVID-19,” said NIDCR Director Rena D ‘Souza, DDS, MS, Ph.D. “The power of this approach is exemplified by the efforts of this scientific team, which has identified a likely role for the mouth in the infection and transmission of SARS-CoV-2, a discovery that adds critical knowledge to fight this disease. ”

The study, published online on March 25, 2021 in Nature Medicine, was led by Blake M. Warner, DDS, Ph.D., MPH, assistant clinical investigator and head of the NIDCR Salivary Disorders Unit, and Kevin M. Byrd, DDS, Ph.D., then an assistant professor at Adams School of Dentistry at the University of North Carolina at Chapel Hill. Byrd is now an Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, United Kingdom, and Paola Perez, Ph.D., of the NIDCR, were the co-first authors.

Researchers already know that the saliva of people with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that the saliva test is almost as reliable as the deep nasal smear for diagnosing COVID-19. What scientists don’t entirely know, however, is where SARS-CoV-2 in saliva comes from. In people with COVID-19 who experience respiratory symptoms, the virus in saliva possibly comes in part from nasal drainage or expectoration expelled from the lungs. But, according to Warner, this may not explain how the virus gets into the saliva of people who do not have these respiratory symptoms.

“Based on data from our labs, we suspect that at least part of the virus in the saliva could come from infected tissues in the mouth itself,” said Warner.

To explore this possibility, the researchers searched oral tissues from healthy people to identify regions of the mouth susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for making “entry proteins” that the virus needs to enter cells. The RNA for two key entry proteins – known as the ACE2 receptor and the TMPRSS2 enzyme – has been found in certain cells of the salivary glands and tissues that line the oral cavity. In a small portion of the cells of the salivary and gingival (gingival) glands, the RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated an increased vulnerability because the virus is thought to need both incoming proteins to gain access to the cells.

“The levels of expression of the input factors are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the tissue that lines the nasal passages of the upper airways,” said Warner.

After the researchers confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with COVID-19. In NIH samples collected from patients with COVID-19 who had died, SARS-CoV-2 RNA was present in just over half of the examined salivary glands. In the salivary gland tissue of one of the people who died, as well as a living person with acute COVID-19, the scientists detected specific viral RNA sequences that indicated that the cells were actively making new copies of the virus – further reinforcing the evidence for infection.

After the team found evidence of infection of the oral tissue, they wondered if those tissues could be a source of the virus in saliva. That seemed to be the case. In people with mild or asymptomatic COVID-19, cells excreted from the mouth into saliva were found to contain RNA from SARS-CoV-2, as well as RNA for incoming proteins.

To determine whether the virus in saliva is infectious, the researchers exposed the saliva of eight people with asymptomatic COVID-19 to healthy cells grown in a dish. The saliva of two of the volunteers led to infection of healthy cells, raising the possibility that even people without symptoms could transmit the infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and viruses in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who had symptoms, those with viruses in their saliva were more likely to report loss of taste and smell, suggesting that oral infection may be behind the oral symptoms of COVID-19.

Taken together, the researchers said, the study results suggest that the mouth, through infected oral cells, plays a greater role in SARS-CoV-2 infection than previously thought.

“When the infected saliva is swallowed or small particles of it are inhaled, we think it can transmit SARS-CoV-2 even more to the throat, lung or even the intestine,” said Byrd.

Further research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth’s involvement in the infection and transmission of SARS-CoV-2 inside and outside the body.

“By revealing a potentially underestimated role for the oral cavity in SARS-CoV-2 infection, our study could open new investigative avenues leading to a better understanding of the course of the infection and the disease. This information can also inform interventions to combat the virus and alleviate the oral symptoms of COVID-19, ”said Warner.

Reference: “SARS-CoV-2 infection of the oral cavity and saliva” by Ni Huang, Paola Pérez, Takafumi Kato, Yu Mikami, Kenichi Okuda, Rodney C. Gilmore, Cecilia Domínguez Conde, Billel Gasmi, Sydney Stein, Margaret Beach, Eileen Pelayo, Jose O. Maldonado, Bernard A. Lafont, Shyh-Ing Jang, Nadia Nasir, Ricardo J. Padilla, Valerie A. Murrah, Robert Maile, William Lovell, Shannon M. Wallet, Natalie M. Bowman, Suzanne L. Meinig, Matthew C. Wolfgang, Saibyasachi N. Choudhury, Mark Novotny, Brian D. Aevermann, Richard H. Scheuermann, Gabrielle Cannon, Carlton W. Anderson, Rhianna E. Lee, Julie T. Marchesan, Mandy Bush, Marcelo Freire, Adam J. Kimple, Daniel L. Herr, Joseph Rabin, Alison Grazioli, Sanchita Das, Benjamin N. French, Thomas Pranzatelli, John A. Chiorini, David E. Kleiner, Stefania Pittaluga, Stephen M. Hewitt, Peter D. Burbelo, Daniel Chertow, NIH COVID-19 Autopsy Consortium, HCA Oral and Craniofacial Biological Network, Karen Frank, Janice Lee, Richard C. Boucher, Sarah A. Teichm nn, Blake M. Warner and Kevin M. Byrd, March 25, 2021, Nature Medicine.
DOI: 10.1038 / s41591-021-01296-8

This research was supported by the NIDCR’s Intramural Research Division. Support also came from the National Institute of Diabetes and Digestive and Renal Diseases (NIDDK), donation DK034987 and intramural NIDDK programs, the National Cancer Institute, the NIH Clinical Center and the National Institute of Allergy and Infectious Diseases. Additional support came from the American Academy of Periodontology / Sunstar Foundation, American Lung Association and the Cystic Fibrosis Foundation.