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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.”
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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Common drug class may increase risk of heart disease
The risk of cardiovascular disease increased in line with how much anticholinergic medication the participants used each year. Those with the highest exposure had a 71 per cent higher risk of a cardiovascular event than people who did not use anticholinergic medication at all.
People who use drugs with anticholinergic effects, including certain antidepressants, drugs for urinary incontinence and common antihistamines, are at higher risk of developing cardiovascular disease.
This is shown in a study from Karolinska Institutet published in BMC Medicine.
Anticholinergic drugs reduce the effect of the neurotransmitter acetylcholine and are commonly prescribed to middle-aged and older people. This large group of drugs includes antihistamines used for allergic conditions, anxiety or insomnia, drugs for urinary incontinence, and certain antidepressants, where tricyclic antidepressants have a strong anticholinergic effect, whereas SSRIs have a weaker effect. A high cumulative use of these drugs, referred to as anticholinergic burden (see fact box), has previously been linked to impaired cognitive ability.
May affect heart regulation
The new study suggests that the drugs may also affect the parasympathetic nervous system and thereby the regulation of the cardiovascular system. The results show that it may be important to monitor the total drug burden in everyday clinical practice.
The study included more than 500,000 people in Stockholm, Sweden, who were 45 years of age or older and had no prior cardiovascular disease, except for hypertension, at the start of the study. The researchers followed the participants for up to 14 years and analysed how the use of anticholinergic drugs was associated with the development of cardiovascular disease.
“Many of these drugs are used by older people and by people with multiple medical conditions. We wanted to investigate whether the total exposure had any significance for the risk of developing cardiovascular disease over time,” says Nanbo Zhu, postdoctoral researcher at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet.
71 per cent higher cardiac risk
The study showed that the risk of cardiovascular disease increased in line with how much anticholinergic medication the participants used each year. Those with the highest exposure had a 71 per cent higher risk of a cardiovascular event than people who did not use anticholinergic medication at all. The association was seen for all types of cardiovascular disease but was particularly clear for heart failure and various forms of arrhythmia.
“Our results indicate that the cumulative drug burden can affect heart regulation, not only in the short term but also over the long term. This does not mean that the drugs should always be avoided, but that exposure should be monitored carefully,” says Hong Xu, assistant professor at the Department of Neurobiology, Care Sciences and Society.
The researchers point out that the study is observational, meaning it cannot establish a causal relationship. Other factors, such as underlying diseases, may also influence the associations.
The work was carried out within the Stockholm CREAtinine Measurements project in collaboration between several research groups at Karolinska Institutet and Region Stockholm. The study was funded by the Swedish Research Council, the Center for Innovative Medicine Foundation, and other foundations. Some researchers report assignments for the pharmaceutical industry, which are disclosed in the scientific publication.
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Mindfulness practices found to significantly reduce depression symptoms, especially for those with early-life adversity
Mindfulness interventions help by regulating our emotions better when different challenges come up. For someone who has experienced childhood neglect or abuse, mindfulness training can help us make sense of that and respond skillfully to this moment in time.
A new study reveals that mindfulness practices may significantly reduce depression symptoms, particularly in people who have experienced early-life adversity, such as childhood abuse and neglect.
Led by Eric Loucks, professor of medicine, epidemiology, and of behavioral and social sciences and director of the Mindfulness Center at Brown, the study enrolled 201 participants, 101 of whom were randomized into the Mindfulness-Based Blood Pressure Reduction Program, while 100 were randomized into an enhanced usual care control, which included home blood-pressure monitors, physician access and health-education materials. Researchers also had a measure of participants’ early-life adversity, particularly their exposure to abuse or neglect.
Loucks and his team followed participants for six months to assess changes in blood pressure, health behaviors and mental health, finding that those in the mindfulness program showed significant improvements in their depression symptoms. Additionally, participants who experienced childhood neglect showed greater improvements in depression symptoms than those who had not. A similar, though less pronounced, trend was observed among people with a history of childhood abuse.
“In this program, that was primarily designed to lower blood pressure while addressing whole-person health, we also saw that mental well-being, particularly around depression symptoms, improved in participants that went through the program,” Loucks said. “The findings suggest that cultivating mindful self-regulation skills–such such as self-awareness, attention control and emotion regulation–may help interrupt maladaptive patterns shaped by past experiences.”
Over the last 15 years, Loucks has been studying social determinants of health such as early-life adversity and its impacts on cardiovascular health, body mass index and blood pressure. “I came to a point where I wanted to not just document it, but do something about it, and I wondered if mindfulness training might help,” he said. “I’d gone through a lot of mindfulness training myself outside of work and started to get trained up in mindfulness programs that are specific to health contexts.”
Loucks began to study the Mindfulness-Based Stress Reduction program, running it through two clinical trials that were funded by the NIH and finding that it reduced blood pressure in both trials. He also wanted to look at the intervention from a whole-person perspective.
“If we look at everyday folks out in the world, those that had exposure to early life adversity, like abuse and neglect, tend to have worse mental health and also worse cardiovascular health,” Loucks said. “Mindfulness interventions help by regulating our emotions better when different challenges come up. For someone who has experienced childhood neglect or abuse, mindfulness training can help us make sense of that and respond skillfully to this moment in time.”
Loucks discussed this work during a keynote address at the U.S. DOHaD Society this year. “It felt like a coming-home moment to see that this intervention, originally developed to address psychosocial factors that influence health, had even stronger effects among people with early-life adversity, particularly on depression,” he said. “It’s been about a 15-year arc of research that culminated in these findings.”
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High-fiber diet linked to reduced risk of heart disease in night shift workers
A moderate intake of about 19 grams of fibre per day was linked to a lower risk for those who worked night shifts regularly. For those who worked night shifts sporadically, about 15 grams was enough. The current recommendation for adults is about 25 grams of dietary fibre per day.
People who work at night have a higher risk of coronary artery disease, a type of heart disease. A new study suggests that a higher fibre intake in the diet may help reduce this risk. The study included over 220,000 adults in the UK and is published in the European Journal of Epidemiology.
The human body is built to sleep at night. This means that working during the night goes against this natural pattern, and can place additional strain on the body, including the heart. Previous research has linked night work to an increased risk of coronary artery disease. Since night work is often unavoidable, the researchers wanted to investigate whether certain dietary habits might have a protective effect.
More fibre associated with lower risk
The researchers used data from 220,000 adults in the UK Biobank (2006–2010) and divided the participants into three groups:
- Day workers
- Shift workers who worked night shifts sporadically
- Regular night shift workers
The participants had completed a detailed questionnaire about their dietary habits. During a follow-up after about 12 years, it was found that night shift workers who consumed little fibre in their diet had a higher risk of coronary artery disease than those who consumed more fibre.
“A moderate intake of about 19 grams of fibre per day was linked to a lower risk for those who worked night shifts regularly. For those who worked night shifts sporadically, about 15 grams was enough. The current recommendation for adults is about 25 grams of dietary fibre per day,” says Diana Nôga, lead author and researcher at Uppsala University.
The researchers stress that the figures from the study are not official dietary recommendations. But they do show a pattern in this UK study: a higher dietary fibre intake was linked to a lower risk of heart disease among night shift workers.
“The link between fibre and a lower risk of heart disease is not just because those who eat more fibre generally have a healthier lifestyle. We know this because we adjusted for various lifestyle factors in the analysis. One possible explanation, supported by previous research, is that fibre in the diet can improve intestinal flora and also reduce lipids, which can be particularly good for the heart in people who work at night,” says Christian Benedict, senior author of the study and Professor of Pharmacology at Uppsala University.
Dietary fibre can support heart health
According to the researchers, an increased intake of fibre-rich foods such as whole grains, vegetables, fruit, legumes and lentils may be a simple way to improve heart health for night shift workers. However, this requires that you do not have any medical obstacles to doing this, such as chronic gastrointestinal diseases.
“Dietary changes should be seen as a complement to, not a substitute for, other heart health-promoting habits such as not smoking, remaining physically active, and getting enough sleep,” says Diana Nôga.
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