COVID-19 Found to Infect Salivary Glands

Authors: Killian Meara March 26, 2021 Contagion Live

People who experienced COVID-19 symptoms and had the virus in their saliva were more likely to report loss of taste and smell, suggesting that oral infection might underlie oral symptoms.

A recent study conducted by investigators from the Wellcome Sanger Institute and the National Institutes of Health, in collaboration with the University of North Carolina at Chapel Hill, and the Human Cell Atlas Oral & Craniofacial Network have found that the COVID-19 virus is able to infect specific cells in the salivary glands of the mouth.

The results from the study were published in the journal Nature Medicine, and was researched as part of the International Human Cell Atlas (HCA) consortium.

“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,” Blake M. Warner, a co-lead author on the study said. “Such information could also inform interventions to combat the virus and alleviate oral symptoms of COVID-19.”

The investigators behind the study analyzed mouth tissue samples using single cell RNA sequencing technology and bioinformatics methods from healthy volunteers. They then looked for cells that expressed two key entry proteins that the virus uses to infect cells, which are ACE2 and TMPRSS2. Following this, the investigators looked at mouth tissue samples from COVID-19 patients who had given biopsy samples or had died.

Findings from the study showed that in the healthy patients, salivary gland ductal cells and some gingival cells expressed both proteins, showing that they were vulnerable to an infection. In the COVID-19 patients, they found SARS-CoV-2 RNA in salivary gland cells, indicating these cells had been infected and found evidence that the virus was replicating in some of these cells.

Additional findings demonstrated that saliva from COVID-19 patients who were asymptomatic or had a mild case contained mouth cells carrying SARS-CoV-2 RNA and RNA for the entry proteins, suggesting they could transmit the virus via saliva.

“Taken together, the study’s findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection than previously thought,” Kevin M. Byrd, a co-lead author on the study said. “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.”

Saliva Could Hold Clues To How Sick You Will Get From COVID-19

Authors: Robert Service Science January 14, 2022

Science‘s COVID-19 reporting is supported by the Pulitzer Center and the Heising-Simons Foundation.

To the known risk factors for developing severe COVID-19—age, male sex, or any of a series of underlying conditions—a new study adds one more: high levels of the virus in your saliva. Standard COVID-19 tests sample the nasal passage. But several new tests look for SARS-CoV-2, the pandemic coronavirus, in saliva, and the new work finds a striking correlation between high virus levels there and later hospitalization or death. If the results are confirmed, saliva tests could help doctors prioritize which patients in the early stages of the disease should receive medicines that drive down levels of the virus.

“I thought it was pretty striking,” says Shane Crotty, a virologist at the La Jolla Institute for Immunology, who was not involved with the research. Crotty notes the results suggest virus levels in saliva reflect viral load deep in the lungs, where the disease does much of its damage in severe cases. “That is a fundamentally valuable insight,” Crotty says.

The new work isn’t the first to link the body’s coronavirus load and disease outcome. Several research groups have found a correlation between high viral levels in the nasal passages at the time of a patient’s hospital admission and ultimate disease severity. But other groups have failed to find that same link.

The standard test to detect SARS-CoV-2 samples nasal mucus using nasopharyngeal (NP) swabs. The procedure is unpleasant, but it is the customary way to sample respiratory pathogens. In recent months, however, several research groups have developed and received emergency use authorization from the U.S. Food and Drug Administration for tests detecting SARS-CoV-2 in saliva.

Yale University researchers were among the first, and the university’s hospitals have been using both saliva and NP swab tests. In both cases, labs analyze the samples using quantitative reverse transcription polymerase chain reaction tests, which can detect genetic material from SARS-CoV-2 and quantify the number of viral particles in each milliliter of sample.

Researchers led by Akiko Iwasaki, an immunologist at Yale, compared viral loads in saliva and NP swabs from 154 patients and 109 people without the virus. They divided the patients into groups that had low, medium, and high viral loads as determined by both types of test. Then they compared those results with the severity of symptoms the patients developed later.

They found that patients who developed severe disease, were hospitalized, or died were more likely to have had high virus loads in their saliva tests, but not in their NP swabs. Viral load in both saliva and nasal mucus declined over time in patients who recovered, but not in those who died.

When Iwasaki and her colleagues reviewed patients’ electronic medical records for markers of disease in the blood, they found that high saliva viral loads correlated with high levels of immune signals such as cytokines and chemokines, nonspecific molecules that ramp up in response to viral infections and have been linked to tissue damage. People with more virus in their saliva also gradually lost certain cells that mount an immune response against viral targets, had lower levels of antibodies targeting the spike protein that the virus uses to enter cells, and were slower to develop the strong immune response needed to knock down the virus in cases where they recovered. The team’s results appeared on 10 January in a preprint that has not been peer reviewed.

Iwasaki and her colleagues argue that saliva may be a better predictor of disease outcome than nasal mucus because the latter comes from the upper respiratory tract, whereas severe disease is associated with damage deep in the lungs. “Saliva may better represent what is going on in the lower respiratory tract,” Iwasaki says, because cilia lining the respiratory tract naturally move mucus up from the lungs into the throat, where it mixes with saliva; coughs have the same effect.

The results don’t have enough statistical power to reveal how much more likely a person with a high saliva viral load is to develop severe COVID-19, Iwasaki says. She is also eager for other groups to replicate the results, especially because efforts to link high NP swab viral loads with disease progression have had mixed results.

If other research confirms the finding, “it would clear away a lot of the fog” around this disease, Crotty says. Monica Gandhi, an infectious disease expert at the University of California, San Francisco, adds that if saliva tests are predictive, they could help doctors identify patients to treat early with either antibodies to reduce viral load or steroids to tamp down overactive nonspecific immune responses.

Saliva tests are cheaper and easier than NP tests, but much less widely available. So confirmation of the new results could bolster efforts to make saliva tests more readily available, says Sri Kosuri, CEO of Octant, Inc., a biotech company. “If this study happened in March, we’d be talking about whether we should be doing NP testing at all,” Kosuri says.

COVID-19 Update: The connection between local and global issues–the Pulitzer Center’s long standing mantra–has, sadly, never been more evident. We are uniquely positioned to serve the journalists, news media organizations, schools, and universities we partner with by continuing to advance our core mission: enabling great journalism and education about underreported and systemic issues that resonate now–and continue to have relevance in times ahead. We believe that this is a moment for decisive action. 

Study reveals mouth as primary source of COVID-19 infection

While most COVID-19 research has focused on the nose and lungs, this is the first study to identify the mouth as a primary site for coronavirus infection and underscores the importance of wearing a face covering and physical distancing.

By University Communications, Thursday, October 29th, 2020

A team of researchers led by the University of North Carolina at Chapel Hill and the National Institute of Dental and Craniofacial Research reveals coronavirus can take hold in the salivary glands where it replicates, and in some cases, leads to prolonged disease when infected saliva is swallowed into the gastrointestinal tract or aspirated to the lungs where it can lead to pneumonia.

While most COVID-19 research has focused on the nose and lungs, this is the first study to identify the mouth as a primary site for coronavirus infection and underscores the importance of wearing a face covering and physical distancing. The results have not been peer-reviewed.

“Our results show oral infection of COVID-19 may be underappreciated,” said senior study author Kevin M. Byrd, research instructor at the UNC Adams School of Dentistry and the Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. “Like nasal infection, oral infection could underlie the asymptomatic spread that makes this disease so hard to contain.”

Byrd along with Blake Warner, chief of the Salivary Disorders Unit at the National Institute of Dental and Craniofacial Research, coordinated the research conducted at the National Institutes of Health, Wellcome Sanger Institute, UNC Marsico Lung Institute and the J. Craig Venter Institute.

Researchers are just beginning to explore the oral symptoms patients experience during COVID-19, such as loss of taste or smell and persistent dry mouth.

In the study, researchers report preliminary results from a clinical trial of 40 subjects with COVID-19 which showed sloughed epithelial cells lining the mouth can be infected with SARS-CoV-2, the coronavirus that causes COVID-19. The amount of virus in patient saliva was positively correlated with taste and smell changes, according to the study.

Relying on oral cell identity maps, researchers also looked at where in the mouth the virus infects. They surveyed oral tissues with the highest levels of ACE2, the receptor that helps coronavirus grab and invade human cells.

Based on ACE2 expression and analysis of cadaver tissue, the most likely sites of infection in the mouth are the salivary glands, tongue and tonsil, the study showed.

The findings provide more evidence of the role of saliva in COVID-19. COVID-19 infection, specifically in the mouth, can allow the virus to spread internally and to others as the infected person breathes, speaks and coughs.

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