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Scientists find evidence that novel coronavirus infects the mouth’s cells

“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.”

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Photo by Kelsey Curtis from Unsplash.com

An international team of scientists has found 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 infection, there are clues the virus can infect cells in other parts of the body, such as the digestive system, blood vessels, kidneys and, as this new study shows, the mouth.

The potential of the virus to infect multiple areas of the body might help explain the wide-ranging symptoms experienced by COVID-19 patients, including oral symptoms such as 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 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. 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 expertise 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 this approach is exemplified by the efforts of this scientific team, who identified a likely role for the mouth in SARS-CoV-2 infection and transmission, a finding that adds to knowledge 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 investigator 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. Byrd is now an Anthony R. Volpe Research Scholar at the American Dental Association Science and Research Institute. 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 people with COVID-19 can contain high levels of SARS-CoV-2, and studies suggest that saliva testing is nearly as reliable as deep nasal swabbing for diagnosing COVID-19. What scientists don’t entirely know, however, is where SARS-CoV-2 in the saliva comes from. In people with COVID-19 who have respiratory symptoms, virus in saliva possibly comes in part from nasal drainage or sputum coughed up from the lungs. But according to Warner, that may not explain how the virus gets into the saliva of people who lack those respiratory symptoms.

“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,” Warner said.

To explore this possibility, the researchers surveyed oral tissues from healthy people to identify mouth regions susceptible to SARS-CoV-2 infection. Vulnerable cells contain RNA instructions for making “entry proteins” that the virus needs to get into cells. RNA for two key entry proteins–known as the ACE2 receptor and the TMPRSS2 enzyme–was found in certain cells of the salivary glands and tissues lining the oral cavity. In a small portion 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 thought to need both entry proteins to gain access to cells.

“The expression levels of the entry factors are similar to those in regions known to be susceptible to SARS-CoV-2 infection, such as the tissue lining the nasal passages of the upper airway,” Warner said.

Once the researchers had confirmed that parts of the mouth are susceptible to SARS-CoV-2, they looked for evidence of infection in oral tissue samples from people with COVID-19. In samples collected at NIH from COVID-19 patients who had died, SARS-CoV-2 RNA was present in just over half of the salivary glands examined. In salivary gland tissue from one of the people who had died, as well as from a living person with acute COVID-19, the scientists detected specific sequences of viral RNA that indicated cells were actively making new copies of the virus–further bolstering the evidence for infection.

Once the team had found evidence of oral tissue infection, they wondered whether those tissues could be a source of the virus in saliva. This appeared to be the case. In people with mild or asymptomatic COVID-19, cells shed from the mouth into saliva were found to contain SARS-CoV-2 RNA, as well as RNA for the entry proteins.

To determine if virus in saliva is infectious, the researchers exposed saliva from eight people with asymptomatic COVID-19 to healthy cells grown in a dish. Saliva from two of the volunteers led to infection of the healthy cells, raising the possibility that even people without symptoms might transmit infectious SARS-CoV-2 to others through saliva.

Finally, to explore the relationship between oral symptoms and virus in saliva, the team collected saliva from a separate group of 35 NIH volunteers with mild or asymptomatic COVID-19. Of the 27 people who experienced symptoms, those with 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.

Taken together, the researchers said, the study’s findings suggest that the mouth, via infected oral cells, plays a bigger role in SARS-CoV-2 infection 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 guts,” said Byrd.

More research will be needed to confirm the findings in a larger group of people and to determine the exact nature of the mouth’s involvement in SARS-CoV-2 infection and transmission within 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 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.

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The look and feel of your neighborhood may affect your sleep

Those living in neighborhoods rated as having a stronger sense of safety tended to sleep longer, and that this rating appeared to be shaped by the streetscape.

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Your neighborhood’s “streetscape”—the physical environment of your street—is something that you have probably never consciously thought about, despite seeing it every day. But what if the streetscape was affecting you on a subconscious level and disrupting your sleep? 

This intriguing question is posed by the findings of a study led by Professor Daisuke Matsushita of the Graduate School of Human Life and Ecology at Osaka Metropolitan University. The research team used AI to analyze more than 200,000 Google Street View images to identify visual neighborhood characteristics. They then linked these characteristics to the self-reported sleep of 1,089 working adults living on the lower floors of apartments in Tokyo, who were most likely to be affected by the streetscape.  

They found that those living in neighborhoods rated as having a stronger sense of safety tended to sleep longer, and that this rating appeared to be shaped by the streetscape. Generally, people slept longer in areas with lots of greenery, such as leafy trees, on the street. Similarly, high “enclosure”—meaning many tall vertical buildings and few wide-open spaces—was also associated with longer sleep and fewer insomnia symptoms. 

However, the study also made a surprising finding. The researchers found that highly walkable streetscapes, such as those with more sidewalks and traffic signs, were associated with a lowered sense of safety and shortened sleep duration.  

This suggests that walkability does not always represent a reassuring environment. Instead, a possible explanation is that streets with extensive pedestrian infrastructure are often busier, more crowded, and used by more strangers, which may be perceived as less safe or less relaxing than quieter residential streets.  

“This study demonstrates the potential for evaluating streetscape characteristics across large geographic areas in a cost-effective manner,” Dr. Matsushita said. “Based on the technique used in this study, cities could potentially measure perceived safety, beauty, liveliness, and enclosure as well as pollution and noise.”  

“We hope that opening up this new perspective creates further possibilities for designing healthier neighborhoods,” he concludes.  

The findings were published in Building and Environment.

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Workout or nap? Either can help your sleepless brain, study finds

People who either completed 20 minutes of moderate-to-vigorous exercise or took a 90-minute nap performed about 22 per cent better on memory tests after 30 hours without sleep than those who did neither.

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A short workout or a nap can help protect memory after a sleepless night, a McGill University-led study has found.

Researchers found people who either completed 20 minutes of moderate-to-vigorous exercise or took a 90-minute nap performed about 22 per cent better on memory tests after 30 hours without sleep than those who did neither. The findings, published in Proceedings of the National Academy of Sciences (PNAS), point to practical ways to counter the effects of sleep deprivation.

“Sleep loss affects nearly every aspect of how we think and function, but many people can’t simply stop what they’re doing and get more sleep,” said senior author Marc Roig, Professor in McGill’s School of Physical and Occupational Therapy. “Our findings show that even a brief bout of exercise may help preserve one of our most important cognitive abilities.”

The study involved 54 healthy young adults who stayed awake for 30 consecutive hours under lab supervision. Participants were then assigned to one of three groups: a 20-minute cycling session, a 90-minute nap or a control condition. Three days later, researchers tested their memory for images they had viewed immediately after the intervention. Those who exercised or napped remembered significantly more images than participants who did neither.

Same result, different pathways

While the memory benefits were nearly identical, brain recordings revealed that exercise and napping helped in different ways.

Napping appeared to help the brain recharge, making it easier to take in and remember new information. Exercise, by contrast, helped the brain use its remaining resources more efficiently, without making participants feel more tired.

The findings could eventually inform fatigue-management strategies in workplaces where sleep loss is common and mistakes can have serious consequences, such as health care, transportation and emergency response.

“A nap isn’t always possible in the middle of a shift,” said first author Madhura Lotlikar, a doctoral candidate in McGill’s Department of Neurology and Neurosurgery. “Exercise is accessible, inexpensive and easy to implement. That makes it a promising tool to help people stay cognitively sharp when sleep is limited.”

The researchers emphasize that exercise cannot replace sleep, but it may help people function better when getting enough rest isn’t possible.

About the study

Protecting episodic memory after sleep loss: Similar benefits of exercise and naps via distinct neural contributions” by Madhura Lotlikar and Marc Roig et al., was published in Proceedings of the National Academy of Sciences of the United States of America.

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Study links coffee consumption to metabolic health and sex hormones

Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.

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Coffee is one of the world’s most widely consumed beverages, and previous research has linked its consumption to a lower risk of conditions such as type 2 diabetes and cardiovascular disease. However, the biological mechanisms behind these benefits remain unclear. A new Finnish study links habitual coffee consumption to healthier body composition and metabolic markers, while revealing distinct associations with sex hormones in men and women.

The study, conducted at the University of Oulu, analysed data from 2,264 participants aged 46 in the Northern Finland Birth Cohort 1966. Researchers examined how habitual coffee consumption was associated with circulating metabolites, cardiometabolic risk markers and sex hormones.

Despite having a similar body mass index (BMI), individuals with higher coffee consumption had lower total and visceral fat and greater skeletal muscle mass than those who consumed less coffee.

In both men and women, higher coffee consumption was correlated with lower circulating levels of branched-chain amino acids, biomarkers that have previously been linked to insulin resistance and an increased risk of type 2 diabetes when chronically elevated.

The strongest sex-specific associations were observed in men. Higher coffee consumption was linked to a more favourable glucose–insulin profile, higher concentrations of total and bioavailable testosterone, and increased levels of sex hormone-binding globulin (SHBG). At the same time, free testosterone and the free androgen index were modestly lower. In women, hormonal associations were more limited and were primarily characterised by higher SHBG and lower measures of free androgens.

“Coffee is consumed by millions of people every day, yet we still know surprisingly little about how it relates to our metabolism and hormones. What stood out in our findings was a distinct hormonal signature that didn’t disappear even after we took into account BMI and lifestyle factors, with several of these associations differing between men and women,” says Luca Verroest, lead author of the study and Doctoral Researcher at the University of Oulu.

The results suggest that hormonal pathways may partly explain the relationship between coffee consumption and metabolic health. However, as this was an observational study, the findings demonstrate associations rather than cause-and-effect relationships.

The study is particularly relevant in Finland, one of the world’s highest coffee-consuming countries, where annual consumption averages around 11.8 kilograms per person.

The researchers say the findings provide a foundation for future studies aimed at determining whether coffee itself drives these biological changes and identifying the compounds responsible. These questions are currently being investigated in animal models, with the long-term goal of progressing to human intervention studies. Further research will be needed before the findings could inform dietary recommendations.

The study, Associations of habitual coffee intake with testosterone and cardiometabolic markers: the Northern Finland Birth Cohort 1966 study, has been published in the European Journal of Nutrition.

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