NewsMakers
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.”
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.
NewsMakers
Coffee and heart health: How many cups of caffeinated coffee are safe to drink each day?
For most adults, consuming up to 400 mg of caffeine/day (or up to 5, 8-ounce cups of caffeinated coffee per day) is safe and appears to be linked to a lower risk of cardiovascular disease for some individuals.
Previous studies have found that caffeine is the world’s most popular stimulant and psychoactive substance, and coffee is the most common way people consume caffeine. The latest research supports the conclusion that for most adults, consuming up to 400 mg of caffeine/day (or up to 5, 8-ounce cups of caffeinated coffee per day) is safe and appears to be linked to a lower risk of cardiovascular disease for some individuals.
However, higher doses of caffeine, such as levels found in energy drinks including energy shots, may cause cardiovascular harm, according to a new American Heart Association scientific statement, “Caffeine and Cardiovascular Disease,” published in the American Heart Association’s flagship peer-reviewed scientific journal Circulation.
“Caffeine consumed in coffee is a key part of daily life for millions of people, and in our review of the most recent research, for most adults, intake of up to 400 mg of caffeine/day, the equivalent of up to 5 cups of caffeinated coffee per day without added sugars or fillers, is safe and does not increase cardiovascular risk,” said Chair of the scientific statement volunteer writing group Gregory M. Marcus, M.D., M.A.S., FAHA, a professor of medicine at the University of California, San Francisco School of Medicine and the associate chief of Cardiology for Research at the University of California, San Francisco Health. “However, high doses of caffeine, such as those found in energy drinks including energy shots, may have harmful effects on the heart and should be avoided.”
The statement authors note that studying the effects of caffeine on the cardiovascular system is challenging. Coffee is the main source of caffeine in most research studies, and the observed cardiovascular effects may be due to other compounds in coffee. For example, experimental studies suggest that the bioactive compounds in coffee may have antioxidant and anti-inflammatory properties, which may help explain some health benefits. It’s also difficult to separate the effects of caffeine from other ingredients usually added to coffee, such as milk, cream, flavored syrups and/or sugar. In addition, most studies on caffeine are observational, meaning they cannot prove cause and effect.
Although coffee is the main source of caffeine for most adults, tea, chocolate, soda and energy drinks, as well as over-the-counter and prescription medications, also contribute to overall caffeine intake. More research is needed about other products with caffeine in order to understand caffeine content and caffeine’s impact on cardiovascular health.
The new scientific statement details the most recent research primarily on caffeinated coffee and the potential impact of caffeine in coffee on high blood pressure, cholesterol, Type 2 diabetes, coronary heart disease, stroke, heart failure, atrial fibrillation, other arrhythmias and other cardiovascular conditions.
Caffeine and cardiovascular health: key things to know
- Based on the results of the latest research studies reviewed, consuming up to 400 mg of caffeine per day, or no more than 3 to 5, 8-ounce cups of regular black caffeinated coffee per day (without sugars, sweeteners, flavors or added fillers), is considered safe for most adults. A regular brewed, non-specialty, caffeinated coffee typically contains 9.4-20.6 mg of caffeine per fluid ounce.
- Consuming caffeinated coffee without added sugars, flavors or cream was linked to a lower risk of Type 2 diabetes, heart disease, stroke, heart failure and some irregular heart rhythms.
- Randomized trials, the most rigorous and reliable type of study design, have shown that caffeine consumption in coffee is associated with a lower risk of atrial fibrillation but also a higher risk of premature ventricular contractions.
- Adding sugar, flavored syrups, milk and/or cream to coffee likely reduces its potential health benefits, and more research is needed to understand the impact of these additives.
- Higher caffeine intake, such as levels found in energy drinks including energy shots, was associated with cardiovascular harm, such as increased risk of high blood pressure and irregular heart rhythm. Energy drink shots may contain 40-69 mg of caffeine per fluid ounce, 3-4 times more caffeine than regular caffeinated coffee.
How does caffeine affect the body?
Caffeine consumed in coffee is metabolized by the liver and generally reaches peak concentration for most people within an hour. However, how quickly individuals process caffeine depends on their genetics, metabolism, age and past caffeine use. When more caffeinated coffee is consumed regularly, some people may develop a tolerance to higher levels of caffeine.
Other people may feel stronger effects from the same amount of caffeine. Short-term effects of caffeine may include temporary increases in blood pressure, heart rate, blood sugar and alertness. Some people may experience heart palpitations and/or sleep disruption.
Specific health impacts of caffeine
- Effects on blood pressure: Studies have found that caffeinated coffee consumption may affect blood pressure differently depending on how much is consumed. In people with optimal blood pressure, drinking 1–3 cups a day was associated with an increased risk of developing high blood pressure, while drinking more than 3 cups per day was associated with a lower risk. High doses of caffeine (such as those from energy drinks or energy shots) can significantly increase blood pressure, especially in people who already have high blood pressure.
- Effects on Type 2 diabetes: Research suggests that caffeinated coffee may reduce insulin sensitivity in the short term. In addition, drinking black, caffeinated coffee (no additives, flavors or sweeteners) regularly was linked to a lower risk of developing Type 2 diabetes. However, this benefit may be due to compounds in coffee other than caffeine. More research is needed to clarify the impact on Type 2 diabetes of caffeinated coffee vs. various compounds in coffee.
- Effects on cholesterol: Data from randomized clinical trials indicate cafestol, a component in both caffeinated and decaffeinated coffee, was associated with higher levels of low-density lipoprotein (also known as “bad” cholesterol). Cafestol is present in unfiltered coffee (such as espresso, French press, Turkish coffee or boiled coffee) but not present in coffee brewed with paper filters or instant coffee. More research is needed to understand which products have higher levels of cafestol and their mechanisms.
- Effects on heart rhythm: The most recent analyses of health measures with self-reported information from participants have found that drinking 1-3 cups of caffeinated coffee per day was not associated with an increased risk of atrial fibrillation or abnormal heart rhythm. However, caffeinated coffee at that same level may be associated with more early beats from the lower chamber of the heart, called premature ventricular contractions (or PVCs). Very high doses of caffeine (such as those in caffeinated energy drinks or energy shots) have been linked to abnormal heart rhythm in people usually considered to have low cardiovascular disease risk, such as healthy adults younger than age 30.
- Effects on heart disease and stroke: Drinking 2-4 cups of caffeinated coffee per day was linked to a lower risk of heart disease, heart failure and stroke. However, drinking more than 4 cups of caffeinated coffee a day may increase the risk of heart failure.
Not all sources of caffeine are the same
More research is necessary to investigate the different health impacts of various types of caffeinated coffee and other products with caffeine, such as tea, soda, energy drinks and energy shots, and foods. There have been fewer studies focused on tea vs. coffee; however, tea has been associated with reduced risk of atrial fibrillation, heart failure and stroke, similar to caffeinated coffee. Energy drinks, bars, gels and caffeine-based supplements often contain other added ingredients that may increase the absorption of caffeine, may accelerate its effects on the body, may raise blood pressure and increase the risk of cardiovascular harm.
More randomized controlled trials investigating the effects of caffeine in coffee and other products that have caffeine on cardiovascular health are needed to better understand how caffeine affects different people and how different sources of caffeine impact heart health. The writing group emphasized that there is also a need for research focused on caffeinated energy drinks and other popular products containing caffeine. Due to the lack of sufficient, rigorous data to develop guidance on recommendations for caffeine intake, caffeine was not referenced in the Association’s 2026 Dietary Guidance to Improve Cardiovascular Health.
“Although research suggests that caffeine consumption may be associated with certain cardiovascular benefits for some people, it’s important to remember that there is no ‘one-size-fits-all’ strategy for safe caffeine consumption. People can respond very differently to caffeine based on various factors, such as age, medications, underlying health conditions, genetics and how quickly their bodies metabolize it. What may be a reasonable amount for one person could cause unwanted effects, such as heart palpitations, anxiety or sleep disruption, in another. That’s why it’s important to pay attention to how your body responds to caffeine and talk with your healthcare team about what is right for you,” Marcus said.
Co-authors are Vice Chair Frank B. Hu, M.D., M.P.H., Ph.D., FAHA; Rob M. van Dam, Ph.D.; Marilyn C. Cornelis, Ph.D.; Thomas A. Dewland, M.D.; JungHee Kang, Ph.D., M.P.H., R.N.; Susanna C. Larsson, Ph.D.; Robert L. Page II, Pharm.D., M.S.P.H., FAHA; and Niyati Parekh, Ph.D., FAHA. Authors’ disclosures are listed in the manuscript.
NewsMakers
Loneliness strongly linked to poorer mental health and wellbeing, study finds
Loneliness was found to be linked with worse general health, including experiencing multiple health conditions. Social isolation is associated with lower wellbeing, too.
People who feel lonely are much more likely to experience poorer mental health and lower wellbeing, a collaborative study led by the University of Bristol, Nesta and Amsterdam UMC has found. Loneliness was also found to be linked with worse general health, including experiencing multiple health conditions. Social isolation is associated with lower wellbeing, too.
Loneliness is increasingly recognised as a major public health issue, with growing evidence connecting it to poorer health. However, it is unclear whether loneliness itself contributes to poor health or whether these links are driven by other factors.
The study, in association with the universities of Oxford and Manchester, combined evidence from three different research methods, including observational analysis, sibling comparisons, and Mendelian randomisation, a genetics-based approach, to build a clearer understanding of these relationships.
Using data from the UK Biobank and large-scale genome-wide association studies, the researchers investigated how both loneliness – the quality of a person’s social relationships; and social isolation – the number of social connections, relate to health and wellbeing. The study is published in Nature Communications.
The research team found that loneliness and social isolation are linked to poorer mental health and reduced wellbeing, with loneliness also associated with worse general health. While the study found no clear evidence of effects on specific physical health conditions, these potential impacts cannot be ruled out.
The findings suggest that loneliness, and potentially social isolation, remain important public health issues, particularly because of their links with mental health, wellbeing and overall health.
As loneliness becomes an increasingly important public health challenge, tackling it could bring benefits for both individuals and society.
Dr Zoe Reed, Research Fellow in the School of Psychology and Neuroscience at the University of Bristol, and corresponding author, said: “Our findings suggest that loneliness, and possibly social isolation, are still important public health concerns, especially for mental health and general health. Supporting people who feel lonely or socially isolated could help improve mental health, wellbeing and overall health.”
Lauren Bowes Byatt, Director of Nesta’s healthy life mission, added: “This research underlines that loneliness is likely to have a detrimental impact on our mental health and wellbeing. While this link may seem obvious, the topic has long been understudied. Studies like this can help to bridge this research gap and by understanding how loneliness or social isolation may be contributing to ill-health, we can get closer to new and more effective solutions.”
The researchers suggest more research is needed to understand exactly how loneliness and social isolation affect health and to develop the most effective ways to reduce their impact.
As the study focused on middle-aged and older adults, future studies should explore whether these patterns are similar in younger people. It will also be important to investigate the effects of persistent or long-term loneliness, as the study measured loneliness at a single point in time.
The paper’s findings add to growing evidence that loneliness and social isolation are not just social issues, they are important public health concerns with wide-ranging implications for wellbeing and mental and physical health. The research reinforces the importance of addressing these issues as part of public health policy and practice.
NewsMakers
Weight loss drugs could help with binge eating disorder
Drugs commonly used for weight loss, known as GLP-1 receptor agonists, have been found to reduce the key symptoms of binge eating disorder
Drugs commonly used for weight loss, known as GLP-1 receptor agonists, have been found to reduce the key symptoms of binge eating disorder, in a new review of evidence led by University College London (UCL) researchers.
The systematic review and meta-analysis, published in eClinicalMedicine, found that weight loss drugs can reduce binge eating episodes, loss-of-control eating and emotional eating, and highlights its potential role to treat binge eating disorder as well as obesity.
Lead author Dr Ilaria Costantini (UCL Psychiatry) said: “Binge eating disorder, where people regularly eat an excessive amount of food while feeling they have lost control, is common and highly impairing, affecting over 17 million people worldwide.
“But treatment options are limited and there are currently no approved medications, so there remains a need for better ways to help people living with this condition. We found evidence that weight loss drugs may help to manage some key symptoms of binge eating disorder.”
In the largest study to date on the subject, the researchers pulled together evidence from 25 randomised controlled trials that took place in 12 countries on four continents, including data from 8,069 participants.
The studies were testing the effects of drugs targeting the appetite-regulating hormone GLP-1 such as semaglutide (often marketed under brand names Ozempic or Wegovy), tirzepatide (also known as Mounjaro) or liraglutide.
These drugs can suppress appetite by targeting the central nervous system and insulin secretion, and they can delay stomach emptying, while also potentially influencing brain processes of reward and impulse control.
The researchers found that the drugs yielded benefits beyond weight loss, including reducing binge eating, loss of control eating and emotional eating.
Participants also reported increased cognitive or dietary restraint (which relates to how much people intentionally limit their eating), but the researchers say more research is needed to understand this link.
The study’s first author, PhD candidate Izzy Emptage (UCL Psychiatry), said: “From the evidence available, we cannot say whether the increase in dietary restraint reflects a positive and helpful form of self-regulation or if it is a more dysfunctional pattern of eating. We hope that future research can clarify whether or not taking weight loss drugs might contribute to more pathological forms of eating restriction such as meal skipping.”
The researchers say their findings demonstrate that weight loss drugs could be an important part of treatment plans for people with binge eating disorder, alongside psychological therapies and social support.
Izzy Emptage added: “Many people with binge eating disorder cannot access weight loss drugs through their public healthcare providers, so many have to seek treatment privately at considerable personal cost.
“We hope that by highlighting the potential of weight loss drugs to help with binge eating symptoms, our findings will lead to further funding of larger high-quality studies in this area, to better understand how this medication could be used in practice and improve treatment options.”
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