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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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Pru Life UK agents, customers, executives celebrate Year of the Wood Dragon

The insurer maintains its top position in New Business Annual Premium Equivalent & total Premium Income from Variable Life Insurance products according to the Insurance Commission’s Life Insurance Sector Quarterly Statistics for Q3 2023.

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With a strengthened commitment to providing better financial protection for every Filipino, Pru Life UK celebrates the start of the Year of the Wood Dragon. Over 200 Pru Life UK leaders, agents, clients, and employees joined and wished everyone PRU Love during the festivities held at the heart of its Escolta branch in Binondo Manila.

The insurer maintains its top position in New Business Annual Premium Equivalent & total Premium Income from Variable Life Insurance products according to the Insurance Commission’s Life Insurance Sector Quarterly Statistics for Q3 2023.

Pru Life UK’s products are made accessible through its over 42,000 digitally-empowered agency workforce and like-minded partners.

The Company recently launched PRULove for Life – an affordable, limited-pay, whole-life participating plan for as low as Php 87 per day* with lifetime coverage up to age 100 and flexible payment terms of 5, 10, 15, or 20 years to pay. To know more about PRULove for Life, talk to your Pru Life UK agent today or visit Pru Life UK’s website.

Pru Life UK is also committed to driving up financial awareness, literacy, and inclusion in the country by leading industry discussions and programs for the community. Its PRUBabies campaign seeks to protect 175,000 newborns with free insurance coverage against select infectious diseases such as Dengue, Typhoid, Measles, and Malaria.

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Eating too much protein is bad for your arteries, and this amino acid is to blame

Consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk.

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University of Pittsburgh School of Medicine researchers discovered a molecular mechanism by which excessive dietary protein could increase atherosclerosis risk. The findings were published in Nature Metabolism.

The study, which combined small human trials with experiments in mice and cells in a Petri dish, showed that consuming over 22% of dietary calories from protein can lead to increased activation of immune cells that play a role in atherosclerotic plaque formation, driving the disease risk. Furthermore, the scientists showed that one amino acid – leucine – seems to have a disproportionate role in driving the pathological pathways linked to atherosclerosis, or stiff, hardened arteries.

“Our study shows that dialing up your protein intake in pursuit of better metabolic health is not a panacea. You could be doing real damage to your arteries,” said senior and co-corresponding author Babak Razani, M.D., Ph.D., professor of cardiology at Pitt. “Our hope is that this research starts a conversation about ways of modifying diets in a precise manner that can influence body function at a molecular level and dampen disease risks.”

According to a survey of an average American diet over the last decade, Americans generally consume a lot of protein, mostly from animal sources. Further, nearly a quarter of the population receives over 22% of all daily calories from protein alone.

That trend is likely driven by the popular idea that dietary protein is essential to healthy living, says Razani. But his and other groups have shown that overreliance on protein may not be such a good thing for long-term health.

Following their 2020 research, in which Razani’s laboratory first showed that excess dietary protein increases atherosclerosis risk in mice, his next study in collaboration with Bettina Mittendorfer, Ph.D., a metabolism expert at the University of Missouri, Columbia, delved deeper into the potential mechanism and its relevance to the human body.

To arrive at the answer, Razani’s laboratory, led by first-authors Xiangyu Zhang, Ph.D., and Divya Kapoor, M.D., teamed up with Mittendorfer’s group to combine their expertise in cellular biology and metabolism and perform a series of experiments across various models – from cells to mice to humans.

“We have shown in our mechanistic studies that amino acids, which are really the building blocks of the protein, can trigger disease through specific signaling mechanisms and then also alter the metabolism of these cells,” Mittendorfer said. “For instance, small immune cells in the vasculature called macrophages can trigger the development of atherosclerosis.”

Based on initial experiments in healthy human subjects to determine the timeline of immune cell activation following ingestion of protein-enriched meals, the researchers simulated similar conditions in mice and in human macrophages, immune cells that are shown to be particularly sensitive to amino acids derived from protein.

Their work showed that consuming more than 22% of daily dietary calories through protein can negatively affect macrophages that are responsible for clearing out cellular debris, leading to the accumulation of a “graveyard” of those cells inside the vessel walls and worsening of atherosclerotic plaques overtime. Interestingly, the analysis of circulating amino acids showed that leucine – an amino acid enriched in animal-derived foods like beef, eggs and milk – is primarily responsible for abnormal macrophage activation and atherosclerosis risk, suggesting a potential avenue for further research on personalized diet modification, or “precision nutrition.”

Razani is careful to note that many questions remain to be answered, mainly: What happens when a person consumes between 15% of daily calories from protein as recommended by the USDA and 22% of daily calories from protein, and if there is a ‘sweet spot’ for maximizing the benefits of protein – such as muscle gain – while avoiding kick-starting a molecular cascade of damaging events leading to cardiovascular disease.

The findings are particularly relevant in hospital settings, where nutritionists often recommend protein-rich foods for the sickest patients to preserve muscle mass and strength.

“Perhaps blindly increasing protein load is wrong,” Razani said. “Instead, it’s important to look at the diet as a whole and suggest balanced meals that won’t inadvertently exacerbate cardiovascular conditions, especially in people at risk of heart disease and vessel disorders.”

Razani also notes that these findings suggest differences in leucine levels between diets enriched in plant and animal protein might explain the differences in their effect on cardiovascular and metabolic health. “The potential for this type of mechanistic research to inform future dietary guidelines is quite exciting,” he said.

Additional authors of the study are Yu-Sheng Yeh, Ph.D., also from Pitt; Alan Fappi, Ph.D. and Vasavi Shabrish, Ph.D., both of the University of Missouri, Columbia; Se-Jin Jeong, Ph.D., Jeremiah Stitham, M.D., Ph.D., Ismail Sergin, Ph.D., Eman Yousif, M.D., Astrid Rodriguez-Velez, Ph.D., Arick Park, M.D., Ph.D., Joel Schilling, M.D., Ph.D., Marco Sardiello, Ph.D., Abhinav Diwan, M.D., Nathan Stitziel, M.D., Ph.D., Ali Javaheri, M.D., Ph.D., Irfan Lodhi, Ph.D., and Jaehyung Cho, Ph.D., all of Washington University School of Medicine, St. Louis; Arif Yurdagul Jr, Ph.D., and Oren Rom, Ph.D., both of the Louisiana State University Health Sciences Center; and Slava Epelman, M.D., Ph.D., of the University of Toronto.

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IRONKIDS Cebu in Lapu-Lapu partners with RLC Residences

This April will be the first event of the partnership as the brand extends their support for the budding young athletes. The aquathlon will see participants from ages 6 to 15 years old complete the race happening at The Reef Island Resort in Mactan.

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The IRONMAN Group Philippines and RLC Residences have announced in 2023 a new partnership—as the residential brand of Robinsons Land Corporation, RLC Residences becomes the title sponsor for IRONKIDS Lapu-Lapu and IRONKIDS Davao for 2024.

This April will be the first event of the partnership as the brand extends their support for the budding young athletes.  The aquathlon will see participants from ages 6 to 15 years old complete the race happening at The Reef Island Resort in Mactan.

RLC Residences Head of Brand Management Mr. Dan Carlo Torres shares his enthusiasm towards the event. “We are very excited to see this partnership unfold. We’ve been very supportive of IRONMAN, especially IRONKIDS because we also believe in the importance of promoting an active and purposeful lifestyle at such a young age and we hope to continuously be part of IRONMAN as we create more vibrant opportunities for our future triathletes,” he added.

“As we aspire to live our best lives, we work to inspire the wider community,” said Ms Princess Galura, Regional Director of the IRONMAN Group Philippines.  “For 10 years, the IRONKIDS has been a part of the Cebuano youth’s stepping stone to either a future in sports, representing the Philippines in international events, as well as planting the seeds of a healthy, sporty lifestyle.  Our partnership with RLC Residences allows us to do so and we are excited to hold the festivities for our youth once again in Lapu-Lapu this April,” she added.

The IRONKIDS event in Lapu-Lapu will feature age group categories for the 6 to 8 years old, 9 to 10 years old, 11 to 12 years old and 13 to 15 years old.  Relay categories are also available for mixed team relay for 6-10 year-olds and 11-15 year-olds. 

Swim and run courses, the transition area and finish line will be at The Reef Island Resort, which is conveniently located in a gated community.  Families who are checked in during race weekend can enjoy amenities of the resort –  including the beach, lap pool and game room.  The resort’s restaurant is operated by Cebu-based top tier chain, Abaca.

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