Findings point to a role for saliva in SARS-CoV-2 transmission
Scientists has found evidence that SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth. The findings 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 virus from infected oral cells. A better understanding of the mouth’s involvement could inform strategies to reduce viral transmission within and outside the body.Source : NIH/National Institute of Dental and Craniofacial Research
SARS-CoV-2, the virus that causes COVID-19, infects cells in the mouth, according to evidence discovered by an international team of scientists. Although it’s well understood that SARS-CoV-2 infection starts in the upper airways and lungs, there’s evidence that the virus can also infect cells in the digestive system, blood vessels, kidneys, and, as this new study reveals, the mouth. COVID-19 patients have a wide range of symptoms, including taste loss, dry mouth, and blistering, which may be explained by the virus’s ability to affect many areas of the body. Furthermore, the findings suggest that saliva laden with virus from infected oral cells may play a role in transmitting SARS-CoV-2 to the lungs or digestive system. A better understanding of the mouth’s role in viral transmission both inside and outside the body may inform strategies to minimize viral transmission both inside and outside the body. Researchers from the National Institutes of Health and the University of North Carolina at Chapel Hill led the team.
“As a result of the National Institutes of Health’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 expertise in oral biology and medicine to addressing critical questions about COVID-19,” said NIDCR Director Rena D’Souza, D.D.S., M.S., Ph.D. “The strength of this approach is demonstrated by the efforts of this scientific team, which identified a possible role for the mouth in SARS-CoV-2 infection and transmission, a finding that contributes to critical knowledge for combating this disease.”
Blake M. Warner, D.D.S., Ph.D., M.P.H., assistant clinical investigator and chief of the NIDCR’s Salivary Disorders Unit, and Kevin M. Byrd, D.D.S., Ph.D., at the time an assistant professor in the University of North Carolina at Chapel Hill’s Adams School of Dentistry, led the study. Byrd is now an American Dental Association Science and Research Institute Anthony R. Volpe Research Scholar. Ni Huang, Ph.D., of the Wellcome Sanger Institute in Cambridge, United Kingdom, and Paola Perez, Ph.D., of the National Institute of Diabetes and Digestive and Kidney Diseases, were co-first authors.
Researchers now know that saliva from COVID-19 patients may produce elevated amounts of SARS-CoV-2, and research show that saliva testing is almost as effective as deep nasal swabbing for diagnosing COVID-19. What scientists do not fully understand, however, is the source of SARS-CoV-2 in saliva. In individuals with COVID-19 who exhibit respiratory symptoms, the virus in saliva may originate in part from nasal drainage or sputum coughed up from the lungs. However, Warner notes that this may not account for how the virus enters the saliva of people who do not exhibit respiratory symptoms.
“Based on laboratory data, we suspected that at least some of the virus in saliva originated from infected tissues in the mouth,” Warner explained. The researchers investigated this possibility by surveying oral tissues from healthy individuals to identify mouth regions susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for generating the “entry proteins” required for the virus to enter the cell. In certain cells of the salivary glands and tissues lining the oral cavity, RNA for two critical entry proteins — the ACE2 receptor and the TMPRSS2 enzyme — was discovered. Both ACE2 and TMPRSS2 RNAs were expressed in a small number of salivary gland and gingival (gum) cells. This increased vulnerability is thought to be due to the virus’s requirement for both entry proteins in order to gain access to cells.
“The entry factors’ expression levels are comparable to those seen in regions considered to be vulnerable to SARS-CoV-2 infection, such as the nasal passages of the upper airway,” Warner said.
After confirming that some areas of the mouth are vulnerable to SARS-CoV-2, the researchers examined oral tissue samples from people with COVID-19 for signs of infection. SARS-CoV-2 RNA was detected in slightly more than half of the salivary glands analyzed in samples obtained at NIH from deceased COVID-19 patients. The scientists found specific viral RNA sequences in salivary gland tissue from one of the deceased, as well as from a living individual with acute COVID-19, indicating that cells were rapidly producing fresh copies of the virus, bolstering the case for infection.
Since discovering signs of oral tissue contamination, the researchers asked whether such tissues might be a reservoir of the virus in saliva. As it appeared, this was the case. Cells shed from the mouth into saliva of people with moderate or asymptomatic COVID-19 were found to contain SARS-CoV-2 RNA as well as RNA for the entry proteins.
To assess if saliva from eight individuals with asymptomatic COVID-19 is contagious, the researchers exposed it to healthy cells grown in a dish. Saliva from two volunteers infected healthy cells, increasing the risk that even those with no symptoms could spread infectious SARS-CoV-2 through saliva.
Finally, the team obtained saliva from a different community of 35 NIH participants with moderate or asymptomatic COVID-19 to examine the association between oral symptoms and virus in saliva. Of the 27 people who reported symptoms, those with virus in their saliva were more likely to report loss of taste and smell, implying that oral infection could underpin COVID-19 oral symptoms.
Taken together, the researchers concluded that the study’s results indicate that the mouth, through infected oral cells, plays a greater role in SARS-CoV-2 infection than commonly believed.
“When contaminated saliva is ingested or inhaled in small fragments, we believe it has the ability to spread SARS-CoV-2 deeper through our mouths, lungs, or even our guts,” Byrd said.
Additional studies would be needed to validate the results in a wider population and to elucidate the precise role of the mouth in SARS-CoV-2 infection and dissemination both inside and outside the body.
“By elucidating a previously unknown function for the oral cavity in SARS-CoV-2 infection, our research can pave the way for new investigative avenues leading to a better understanding of infection and disease progression. Additionally, this knowledge may be used to advise therapies aimed at combating the virus and alleviating COVID-19 oral symptoms “As Warner said.
This study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases’ Division of Intramural Research. Additionally, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) provided support by grant DK034987 and intramural services at NIDDK, the National Cancer Institute, the National Institutes of Health Clinical Center, and the National Institute of Allergy and Infectious Diseases. The American Academy of Periodontology/Sunstar Foundation, the American Lung Association, and the Cystic Fibrosis Foundation have provided additional funding.