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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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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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Gene therapy has potential to cure thalassemia patients from blood disorder

Thalassemia is a blood disorder that affects the body’s ability to produce red blood cells, and hemoglobin, the protein that carries oxygen in red blood cells. Even with blood transfusion and appropriate iron chelation therapy; patients can develop iron overload, with potential to damage the liver, heart, and endocrine system.

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Gene therapy could pave the way for patients with the inherited blood disorder thalassemia to stop or significantly reduce blood transfusions and transform their daily lives, says an expert at a top American hospital, Cleveland Clinic.

Dr. Rabi Hanna, a pediatric hematologist-oncologist, said: “Thalassemia is a disease that can be cured, with gene therapy as a novel step that uses the patients’ own hematopoietic stem cells to produce healthier red blood cells and fix their blood disorder. Thalassemia patients who have received gene therapy have either eliminated or significantly reduced the amount of blood transfusions needed to manage their condition. With gene therapy, we can remove the challenges that thalassemia patients face to give them the courage to pursue their goals and dreams, whether in education, careers, or families.”

Thalassemia is a blood disorder that affects the body’s ability to produce red blood cells, and hemoglobin, the protein that carries oxygen in red blood cells. Even with blood transfusion and appropriate iron chelation therapy; patients can develop iron overload, with potential to damage the liver, heart, and endocrine system.

There are two type of thalassemia, alpha and beta, depending on the defects that can occur in the protein chains that make up hemoglobin. Patients with alpha thalassemia tend to be silent carriers without symptoms, while patients with beta thalassemia major will have major symptoms early after birth and require frequent red blood transfusions. Moderate and severe thalassemia cases are usually diagnosed with early childhood blood tests. Married couples can also have genetic tests that can predict the risk of thalassemia and related blood disorders.

Worldwide, there are 270 million carriers with abnormal hemoglobin and thalassemia, with 300,000-400,000 babies born with serious hemoglobin disorders annually, according to the US National Institute of Health. It is estimated that 90 percent of those births are in low- or middle-income countries, especially in the Middle East, South and Southeast Asia, the Mediterranean, Africa, and the South Pacific. Recognizing this, International Thalassemia Day’s theme for 2021 is “Addressing Health Inequalities Across the Global Thalassemia Community.”

In contrast to time-consuming, life-long blood transfusions, gene therapy could be a one-time therapy and provide a potential cure. Despite that, the allogeneic bone marrow transplant is currently the only available option with the potential to correct the genetic deficiency in Transfusion-dependent Thalassemia (TDT), but it has possible complications such as graft failure, graft-versus-host disease (GvHD), and opportunistic infections, particularly in patients who undergo non-sibling matched allogeneic HSCT. Gene therapy, in contrast, uses the patient’s own cells and eliminates the risk of GVHD.

The challenge in Dr. Hann’s opinion is how we can make this therapy available worldwide, especially in developing countries, where most of the patients are, globally.

The European Medicines Agency has given conditional marketing authorization to one form of genetically modified products for beta-thalassemia. In the United States, there are currently clinical trials for gene therapy, and this therapy is under review by Food and Drug Administration – which experts hope could lead to authorization later in 2021.

In recent phase 1-2 studies of gene therapy for 22 patients, all of them had reduced or eliminated the need for long-term red blood cell transfusions. Of the 13 alpha-thalassemia patients, 12 stopped receiving red blood cell transfusions. For the nine beta-thalassemia patients, three stopped red blood cell transfusions, and the remaining six patients saw their median annualized transfusion volume decrease by 73 percent.

“While gene therapy is a promising cure for transfusion-dependent thalassemia, many patients do not know the whole process – including chemotherapy to get rid of the old bone marrow and create space for the new modified stem cells. This will currently require admission to hospital for four to 6 weeks until new the stem cells are working and able to produce white blood cells, platelets and healthier red blood cells,” added Dr. Hanna. “We are hopeful that in the future we can target the bone marrow more selectively using reduced intensity chemotherapy or other medication to avoid the acute and long-term toxicity associated with high doses of chemotherapy.”

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Asthma both under-diagnosed and misdiagnosed

Proper medical diagnosis of asthma could mean that about one-third of people assumed to suffer from the disease could be weaned off long-term medications, impacting millions of people worldwide, says an expert at a top American hospital, Cleveland Clinic.

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Proper medical diagnosis of asthma could mean that about one-third of people assumed to suffer from the disease could be weaned off long-term medications, impacting millions of people worldwide, says an expert at a top American hospital, Cleveland Clinic.

Dr. Joe Zein, who specializes in pulmonary medicine at Cleveland Clinic, said: “Asthma impacts millions of people, and proper diagnoses and treatment are vital to treat asthma early before any damage occurs to the airway. Studies show that one-third of patients thought to have asthma are misdiagnosed by doctors, and 15% of asthma patients taking medication long term do not have an objective diagnosis. Proper diagnosis can ensure that patients receive the right treatment, reduce triggers, and lead healthier lives.”

A study in the Journal of American Medicine (JAMA) found that 33% of randomly tested asthma patients could be safely weaned off their medications, and did not need long-term inhaled steroids.

Asthma is one of the world’s major chronic diseases, impacting more than 339 million people globally, and the most common, non-communicable disease among children, according to the World Health Organization. At the same time, studies have found that asthma is under-diagnosed and under-treated.

Commenting on World Asthma Day 2021’s theme of “Uncovering Asthma Misconceptions,” Dr. Zein emphasized that while some people assume otherwise, asthma tests are often quick and easy. Common diagnostic methods include a spirometry test that measures the airflow through the lungs, and a methacholine challenge test that evaluates how reactive lungs are to changes in the environment. Healthcare practitioners may also request chest x-rays, and blood, skin, or allergy tests.

Asthma patients can suffer from chest tightness, pain, or pressure; coughing; and shortness of breath or wheezing. An asthma attack restricts airflow due to tightened and inflamed airways, and mucus clogs.

Treatment can include anti-inflammatory medicines that make it easier for air to enter and exit the lungs, bronchodilators that relax the airway muscles, or biologic therapies that target specific molecules.

Asthma, which has both genetic and environmental causes, has a wide range of triggers – especially in people’s own homes and neighborhoods. The most common asthma triggers are dust mites, pet dander, pollen and ragweed, pests such as cockroaches and mice, and mold. Tobacco smoke from the patient themselves or from secondhand smoke, air pollution, and exercise can also all trigger asthma attacks.

“People with asthma may not want to get rid of their pets, especially cats or dogs,” added Dr. Zein. “If asthma patients have to keep their pets in the house, they should keep pets outside of the bedroom, and replace any thick carpets with tile or hardwood to reduce pet dander. Asthma patients should also wash their bedding with hot water, vacuum often to remove dust, and put in de-humidifiers in any damp areas of the house.”

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Does listening to calming music at bedtime actually help you sleep?

Listening to calming music at bedtime improved sleep quality in older adults, and calming music was much better at improving sleep quality than rhythmic music.

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A new study published in the Journal of the American Geriatrics Society has found that listening to music can help older adults sleep better.

Researchers from the National Cheng Kung University Hospital in Taiwan combined the results of past studies to understand the effect that listening to music can have on the quality of older adults’ sleep. Their work suggests that:

  • Older adults (ages 60 and up) living at home sleep better when they listen to music for 30 minutes to one hour at bedtime.
  • Calm music improves older adults’ sleep quality better than rhythmic music does.
  • Older adults should listen to music for more than four weeks to see the most benefit from listening to music.

Why Older Adults Have Trouble Getting a Good Night’s Sleep

As we age, our sleep cycles change and make a good night’s sleep harder to achieve. What does it really mean to get a good night’s sleep? If you wake up rested and ready to start your day, you probably slept deeply the night before. But if you’re tired during the day, need coffee to keep you going, or wake up several times during the night, you may not be getting the deep sleep you need. According to the National Institute on Aging, older adults need seven to nine hours of sleep each night.

But studies have shown that 40 to 70 percent of older adults have sleep problems and over 40 percent have insomnia, meaning they wake up often during the night or too early in the morning. Sleep problems can make you feel irritable and depressed, can cause memory problems, and can even lead to falls or accidents.

How the Researchers Studied the Effect of Music on Older Adults’ Quality of Sleep

For their study, the researchers searched for past studies that tested the effect of listening to music on older adults with sleep problems who live at home. They looked at five studies with 288 participants. Half of these people listened to music; the other half got the usual or no treatment for their sleep problems. People who were treated with music listened to either calming or rhythmic music for 30 minutes to one hour, over a period ranging from two days to three months. (Calming music has slow tempo of 60 to 80 beats per minute and a smooth melody, while rhythmic music is faster and louder.) All participants answered questions about how well they thought they were sleeping. Each participant ended up with a score between 0 and 21 for the quality of their sleep.

The researchers looked at the difference in average scores for:

  • people who listened to music compared to people who did not listen to music;
  • people who listened to calm music compared to people who listened to rhythmic music;
  • and people who listened to music for less than four weeks compared to people who listened to music for more than four weeks.

What the Researchers Learned

Listening to calming music at bedtime improved sleep quality in older adults, and calming music was much better at improving sleep quality than rhythmic music. The researchers said that calming music may improve sleep by slowing your heart rate and breathing, and lowering your blood pressure. This, in turn helps lower your levels of stress and anxiety.

Researchers also learned that listening to music for longer than four weeks is better at improving sleep quality than listening to music for a shorter length of time.

What this Study Means for You

If you’re having trouble sleeping, listening to music can be a safe, effective, and easy way to help you fall and stay asleep. It may also reduce your need for medication to help you sleep.

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