TORONTO -- A new study has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects the cells in the mouth including the salivary glands – which may explain some COVID-19 symptoms such as loss of taste and dry mouth.
The findings of the study led by the U.S. National Institutes of Health (NIH) and the University of North Carolina at Chapel Hill also “point to the possibility that the mouth plays a role in transmitting SARS-CoV-2 to the lungs or digestive system via saliva laden with the virus from infected oral cells,” according to a press release.
The study, published in Nature Medicine, focused on discovering where SARS-CoV-2 in the saliva comes from as it is well established that people diagnosed with COVID-19 contain high levels of the virus in their saliva.
People with COVID-19 who have respiratory symptoms may have the virus in their saliva from nasal drainage of sputum coughed up from the lungs, the release states, but the researchers said it may not explain how the virus gets into the saliva of people who lack those symptoms.
Blake Warner, lead study author and assistant clinical director and chief of the National Institute of Dental and Craniofacial Research (NIDCR), said in the release that “based on the data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself.”
To investigate this, scientists surveyed oral tissue collected from healthy people in order to identify mouth regions susceptible to SARS-CoV-2 infection. The vulnerable cells contained ribonucleic acid (RNA) molecules that have instructions for making “entry proteins” or “doorways” that the virus needs to be able to get into the cells and infect it.
RNA for two key entry proteins known as the ACE2 receptor and the TMPRSS2 enzyme were found in cells of the salivary glands and in tissues lining the oral cavity, which indicated “increased vulnerability because the virus is thought to need both entry proteins to gain access to cells,” the release states.
Warner said that those factors are similar to the ones found in regions known to be susceptible to SARS-CoV-2 infection, such as the lining of the nasal passage and upper airways.
The next step for the researchers after confirming that parts of the mouth are susceptible to SARS-CoV-2 was to look for evidence of infection in oral tissue samples from people with COVID-19. In samples collected at the NIH from COVID-19 patients who had died, SARS-CoV-2 RNA was found in “just over half” of the salivary glands examined. Researchers also found the specific sequences of RNA that indicated cells were actively making new copies of the virus in a living person who had acute COVID-19.
The study further found that salivary gland tissue infected with SARS-CoV-2 could be the source of the virus in saliva. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to have the RNA entry proteins and SARS-CoV-2 RNA.
In order to determine whether virus found in saliva is infectious, researchers took saliva from eight people with asymptomatic COVID-19 and exposed it to healthy cells grown in a dish.
Saliva from two of the eight subjects led to infection of the healthy cells – raising the possibility that asymptomatic COVID-19 patients might transmit infectious SARS-CoV-2 to others through saliva, according to the study.
A final aspect of the study was to explore the relationship between oral symptoms of COVID-19 and virus in saliva. Researchers collected saliva from a group of 35 volunteers with mild or asymptomatic COVID-19. Of the 27 people who were experiencing oral symptoms, those with the virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms of COVID-19.
The study’s findings suggest that the mouth, via infected oral tissue cells, plays a bigger role in SARS-CoV-2 infections than previously thought.
“When infected saliva is swallowed or tiny particles of it are inhaled, we think it can potentially transmit SARS-CoV-2 further into our throats, our lungs, or even our gut,” said Kevin Byrd, second author of the study and assistant professor in dentistry at the University of North Carolina Chapel Hill, in the release.
The researchers hope to confirm their findings in a larger group of people and to determine the exact nature of the part the mouth plays in SARS-CoV-2 infection and transmission, according to the release.
"By revealing a potentially underappreciated role for the oral cavity in SARS-CoV-2 infection, our study could open up new investigative avenues leading to a better understanding of the course of infection and disease. Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19," Warner said.
