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The mouth and SARS-CoV-2: Evidence of infected cells suggests key role in infection, transmission

It remains unknown whether the SARS-CoV-2 virus can directly infect or replicate in tissues inside the oral cavity, and the origin of viral load in the mouth is also unclear. (Image: Anusorn Nakdee/Shutterstock)
By Jeremy Booth, Dental Tribune International
April 13, 2021

BETHESDA, Md., U.S.: COVID-19 can cause a number of symptoms in the oral cavity, such as lesions, ulcerations and a loss of taste, and yet the role of the mouth in SARS-CoV-2 infection and transmission is poorly understood. A study by an international team of scientists has found evidence that the virus infects cells in the mouth. This finding, the researchers say, shows that the oral cavity could play an important role in SARS-CoV-2 infection and underscores the need for adequate prevention measures in dental settings.

According to the study, which was undertaken under the auspices of the National Institutes of Health (NIH) in the U.S., the nasal–lung axis has been the primary focus of research into SARS-CoV-2 infection, and it remains unknown whether the virus can directly infect or replicate in tissues inside the oral cavity. Saliva testing has been shown to be reliable in detecting the virus, but the origin of SARS-CoV-2 viral load in the mouth is unclear.

The researchers outlined the importance of understanding more about the relationship between the virus and oral tissues such as salivary glands and mucosa. “This is critical because, if these are sites of early infection, they could play an important role in transmitting the virus to the lungs or the gastrointestinal tract via saliva,” they wrote. In an NIH press release, co-leading author Dr. Blake M. Warner, assistant clinical investigator and head of the Salivary Disorders Unit at the National Institute of Dental and Craniofacial Research (NIDCR), said: “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.”

“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”
– Dr. Blake M. Warner, NIDCR

In the study, the researchers assessed oral tissues from healthy people to identify regions of the mouth that were susceptible to SARS-CoV-2 infection. They also assessed transcripts using droplet digital polymerase chain reaction in a cohort of COVID-19 autopsy tissues taken from the salivary glands and mucosal sites of 18 patients. They detected the virus in more than half (57%) of the salivary glands, with higher viral loads being detected in the minor salivary glands than in the paired parotid salivary glands. Infection was also detected in submandibular glands and in lining cells of the oral mucosa, and it was found that minor and major salivary glands were susceptible sites for SARS-CoV-2 infection, replication and immune cell activation. The researchers also found that acellular and cellular salivary fractions from asymptomatic individuals transmitted the virus ex vivo and that the viral load in saliva correlated with COVID-19 symptoms in the mouth, including loss of taste.

Collectively, the findings of the study indicate that the mouth—via infected oral cells—plays a greater role in SARS-CoV-2 infection than was previously thought, the authors wrote. In the press release, co-leading author Dr. Kevin M. Byrd, Anthony R. Volpe research scholar at the American Dental Association Science and Research Institute, explained: “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 guts.”

Speaking to Dental Tribune International (DTI), Warner said that the study findings showed direct evidence of the tissues of the mouth being a reservoir for SARS-CoV-2 and of the potential infectiousness of the virus in saliva. He said that this was a fact that many healthcare providers had assumed to be plausible. He explained: “From a practice standpoint, I think this should galvanize providers into using personal protective equipment [PPE], such as N95 masks and face shields/eye protection, during aerosol-generating procedures. Methods to manage aerosols during procedures, such as high-speed suction and other aerosol-mitigating devices and effective ventilation—increasing the amount of outside air exchange—likely adequately reduce transmission risk in conducting dental procedures.”

Warner added: “Although speculative, I think it is a testament to dental providers’ effective use of PPE during the COVID-19 pandemic that has led to only a few reports of person-to-person transmission in dental offices, despite the high hypothetical risk.”

“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 guts” – Dr. Kevin M. Byrd, American Dental Association Science and Research Institute

Warner said that he and his fellow researchers planned to extend the research by examining additional types of mouth tissue and looking at why some COVID-19 patients experience loss of taste and or smell. “Another avenue of investigation would be the better understanding of the immunopathological consequences of SARS-CoV-2 infection in the mouth and the connection to reported oral symptoms such as taste loss, dry mouth and oral lesions. That is to say, what are the spectrum of oral lesions that develop after SARS-CoV-2 infection?” Warner added.

In the press release, Warner commented: “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.”

The study was funded by the NIH and led by researchers at NIH and the University of North Carolina at Chapel Hill. Speaking to DTI, Jeff D. Ventura, director of communications and health education at NIDCR, explained that NIDCR is working closely with other NIH institutes and centers to prioritize research in the fight against COVID-19. “Whether funding extramural research or conducting our own studies at NIH’s main campus in Maryland, NIDCR is committed to answering essential scientific questions about this novel coronavirus,” he said. 

Examples of NIH-funded COVID-19 research initiatives can be found here and here. 

The study, titled “SARS-CoV-2 infection of the oral cavity and saliva,” was published on March 25, 2021, in Nature Medicine. 

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