Researchers discover proof that SARS-CoV-2 infects cells in the mouth

Researchers discover proof that SARS-CoV-2 infects cells in the mouth


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  • Source: NIH/National Institute of Dental and Craniofacial Research

  • Date: 25 Mar,2021

An international group of scientists has discovered evidence that SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth.

While it’s well known that the upper airways and lungs are primary sites of SARS-CoV-2 disease, there are clues the virus can infect cells in different parts of the body, like the digestive system, blood vessels, kidneys, and, as this new study showsthe mouth.

The potential of this virus to infect multiple regions of the body may help clarify the wide-ranging symptoms characterized by COVID-19 patients, including oral symptoms like taste loss, dry mouth, and blistering.

Moreover, the findings point to the possibility that the mouth plays a role in transmitting SARS-CoV-2 to the lungs or digestive tract via saliva laden with virus from infected oral cells.

A better comprehension of the mouth’s involvement could inform strategies to reduce viral transmission within and outside the body. The team was led by researchers at the National Institutes of Health and the University of North Carolina at Chapel Hill.

“Due to NIH’s all-hands-on-deck response to the pandemic, researchers at the National Institute of Dental and Craniofacial Research were able to quickly pivot and apply their experience in oral biology and medicine to answering key questions about COVID-19,” said NIDCR Director Rena D’Souza, D.D.S., M.S., Ph.D.”The power of the approach is exemplified by the efforts of this scientific team, who identified a likely role for the mouth in SARS-CoV-2 disease and transmission, a finding that adds to understanding critical for combatting this disease.”

The study, published online March 25, 2021, in Nature Medicine, was led by Blake M. Warner, D.D.S., Ph.D., M.P.H., assistant clinical researcher and chief of NIDCR’s Salivary Disorders Unit, and Kevin M. Byrd, D.D.S., Ph.D., at the time an assistant professor in the Adams School of Dentistry at the University of North Carolina at Chapel Hill. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, U.K., and Paola Perez, Ph.D., of NIDCR, were co-first authors.

Researchers already know that the saliva of individuals with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that saliva testing is nearly as dependable as heavy nasal swabbing for diagnosing COVID-19.

What scientists do not fully know, however, is where SARS-CoV-2 from the saliva comes from.

But according to Warner, that might not clarify how the virus gets into the saliva of individuals who lack those respiratory symptoms.

To explore this possibility, the researchers surveyed oral cells from healthy individuals to detect mouth regions vulnerable to SARS-CoV-2 infection.

Vulnerable cells contain RNA directions for making”entry proteins” that the virus should get into cells. RNA for 2 key entry proteins–known as the ACE2 receptor and the TMPRSS2 enzyme–was discovered in certain cells of the salivary glands and cells lining the oral cavity.

Based on data from our laboratories, we suspected at least some of the virus in saliva could be coming from infected tissues in the mouth itself.”

Blake M. Warner, DDS, PhD, MPH, Assistant Clinical Investigator and Chief of Salivary Disorders Unit, National Institute of Dental and Craniofacial Research

In a small segment of salivary gland and gingival (gum) cells, RNA for both ACE2 and TMPRSS2 was expressed in the same cells. This indicated increased vulnerability because the virus is supposed to need both entry proteins to gain access to cells.

“The expression levels of these entrance factors are similar to those in regions known to be prone to SARS-CoV-2 infection, like the tissue lining the nasal passages of the upper airway,” Warner said.

Once the investigators had confirmed that portions of the mouth are prone to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from individuals with COVID-19.

In salivary gland tissue from one of the people who had died, as well as from a living individual with acute COVID-19, the scientists detected particular sequences of viral RNA that indicated cells were actively making new copies of the virus–further strengthening the evidence for disease.

Once the group had found evidence of oral tissue infection, they wondered whether those tissues might be a source of the virus in saliva. This appeared to be true. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to comprise SARS-CoV-2 RNA, in addition to RNA for the entrance proteins.

To find out whether the virus in saliva is contagious, the researchers exposed saliva from eight individuals with asymptomatic COVID-19 to healthy cells grown in a dish. Saliva from among the volunteers resulted in the infection of the healthy cells, raising the possibility that even people without symptoms may transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the connection between oral symptoms and virus in saliva, the group collected saliva from a different set of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 individuals who experienced symptoms, those with the virus in their saliva were more likely to report loss of taste and odor, suggesting that oral infection might underlie oral signs of COVID-19.

Taken together, the researchers said, the study’s findings indicate that the mouth, through infected oral cells, plays a larger role in SARS-CoV-2 disease than previously thought.

“When infected saliva is swallowed or tiny particles of it are inhaled, we think it can possibly transmit SARS-CoV-2 farther into our throats, our lungs, as well as our guts,” said Byrd.

More research will be needed to confirm the findings in a larger group of people and to ascertain the exact nature of the mouth’s participation in SARS-CoV-2 disease and transmission inside and outside the body.

“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 comprehension of the course of infection and disease. Such information could also inform interventions to combat the virus and relieve oral signs of COVID-19,” Warner said.


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