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
Heart disease risk may start in the womb, study finds
Young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.
A child’s future heart health may be partially shaped before they are born, reports a new Northwestern Medicine study that found pregnancy complications are linked to poorer cardiovascular health in offspring more than 20 years later.
The study found that young adults whose mothers had high blood pressure during pregnancy — either pregnancy-associated hypertension, pre-eclampsia or eclampsia — had more signs of early arterial injury, higher blood pressure, higher body mass index and higher blood sugar than peers.
The authors said the study adds to growing evidence that cardiovascular risk may be transmitted across generations through a combination of biological, environmental and behavioral factors.
“That means we must make sure people maintain good health from childhood into young adulthood, so that if or when someone becomes a parent, they pass on the best opportunity for good health to their children,” said study senior author Dr. Nilay Shah, assistant professor of medicine in the division of cardiology at Northwestern University Feinberg School of Medicine.
How the study was conducted
Shah and colleagues evaluated nearly 1,350 mother-child pairs from the Future of Families and Child Well-Being Study, which enrolled mothers and children at birth between 1998 and 2000 across 20 U.S. cities. The children were then followed into adulthood.
Using delivery hospitalization records, the Northwestern scientists first identified whether mothers experienced pregnancy complications, including high blood pressure during pregnancy, gestational diabetes (high blood sugar during pregnancy) or preterm birth (before 37 weeks of pregnancy).
The three pregnancy complications are on the rise, and affect almost one in four pregnancies in the U.S.
The research team then analyzed cardiovascular health of offspring at age 22, using blood pressure measurements, blood testing, body mass index assessments and carotid artery ultrasounds to look for signs of artery injury.
Finally, the scientists compared participants with and without exposure to each pregnancy complication and adjusted for factors like income, education, difference in birth weight and smoking during pregnancy.
Key findings
At around age 22, participants whose mothers had high blood pressure during pregnancy had:
- Higher body mass index (+2.8 BMI points)
- Higher diastolic blood pressure (+2.3 mm Hg)
- Higher blood sugar levels (+0.2% HbA1c)
- Thicker artery walls (~0.02 mm)
While the difference in artery wall thickness may seem small, the study authors said it corresponds to roughly three to five years of additional vascular aging. That means arteries looked older and less healthy than expected, which raises the risk of future heart disease.
Other pregnancy complications also showed some long-term effect:
- Exposure to gestational diabetes was linked to worse blood pressure and some evidence of artery thickening
- Being born preterm was associated with higher blood sugar levels
‘Most heart disease is preventable’
With pregnancy complications on the rise in the U.S., Shah said the study provides compelling evidence that improving health before and during pregnancy could help reduce heart disease risk in the next generation.
“There is evidence that both parents’ health at the time of conception and during pregnancy influences a child’s health,” he said. “So, promoting health from an early age, like exercising regularly, eating healthfully, never smoking and getting enough sleep, is not just meant for an individual, but doing so may help future generations be healthier, too.”
Shah also emphasizes that risk is not destiny.
“The good news is that most heart disease is preventable,” he said. “If you experienced high blood pressure or high blood sugar during pregnancy, or your child was born early, it does not absolutely mean that your child will have worse health as adults. But I would encourage you to pay attention now to your child’s health behaviors.
“What children learn in childhood sets the stage for their health across their lives. If you are wondering whether your children’s behaviors are healthy, or are considering making a change, please speak with your child’s pediatrician for advice and guidance.”
Other Northwestern co-authors include Emily Lam, Abigail Gauen, Dr. Sadiya Khan, Alexa Freedman and Norrina Allen.
NewsMakers
Viagra could hold key to halting Peyronie’s disease
Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease.
Combining two widely prescribed drug classes could provide the first effective treatment for early-stage Peyronie’s disease, according to a study published in The Journal of Sexual Medicine.
Peyronie’s disease (PD) is caused by the development of fibrotic scar tissue within the penis, leading to pain, curvature, sexual dysfunction and, in many cases, significant psychological distress. It affects an estimated 10 per cent of men during their lifetime, but despite its prevalence, treatment options are limited, particularly in the early phase of the condition.
The study, carried out by Anglia Ruskin University (ARU) and University College London Hospital (UCLH), found that combining phosphodiesterase type 5 (PDE5) inhibitors such as sildenafil (Viagra) and tadalafil (Cialis) with selective oestrogen receptor modulators (SERMs), including tamoxifen, may slow or even stop disease progression when given early.
The clinical study, carried out by Professor David Ralph of UCLH, evaluated outcomes in 133 men diagnosed with acute Peyronie’s disease who were treated with the drug combination for three months. Their results were compared with a smaller group of patients receiving standard care, which included giving vitamin E or no treatment at all. Standard care did not include surgery.
The study found 43 per cent of patients on the combination experienced an improvement in penile curvature, almost three times higher than in the standard‑care group (15 per cent).
At the start of treatment, 65 per cent of patients in the combination group reported pain during erections. After three months, that figure had fallen to just 1.5 per cent. By comparison, pain prevalence in the standard‑care group fell from 50 per cent to 27 per cent.
The clinical findings build on earlier laboratory work led by Professor Selim Cellek at ARU’s Fibrosis Research Group. Over the course of several years, Professor Cellek’s team screened 1,953 FDA‑approved drugs to identify compounds capable of blocking the transformation of fibroblasts into myofibroblasts, the key cells responsible for fibrosis. PDE5 inhibitors and SERMs emerged as particularly effective, and when used together demonstrated an effect greater than either drug alone.
Currently, there are no approved oral therapies proven to prevent early disease progression, forcing patients in the acute phase to wait until the condition stabilises before they can be offered treatments including injections or surgery.
Professor Cellek said: “Positive findings from this pilot clinical study validate our drug‑screening approach in the lab. It shows how repurposing well‑known medicines can accelerate progress in areas of unmet clinical need.
“Because both PDE5 inhibitors and SERMs are already widely used in clinical practice and have established safety profiles, the approach could be readily adoptable if confirmed in larger studies.
“These results suggest that early intervention targeting fibrosis could change how we treat Peyronie’s disease. Repurposing existing drugs may allow us to move from managing symptoms to modifying the disease itself.”
Professor David Ralph, Professor of Urology at UCLH, said: “This paper confirms the basic science research with regards to halting the progression of Peyronie’s disease. In previous papers we have noted that tamoxifen and PDE5 inhibitors inhibit the transformation of fibroblasts into myofibroblasts and therefore contraction of the plaque.
“This has now been put into clinical practice where this paper shows that when tamoxifen and a PDE5 inhibitor are combined, there is statistically less progression of the disease and improvement in curvature compared to the control arm. This is where from bench to clinical practice prevails and hopefully now a prospective clinical trial can be initiated.”
NewsMakers
Healthier brains may be more resilient to early Alzheimer’s disease
Maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function.
A healthy brain may help protect thinking and memory skills from the early effects of Alzheimer’s disease, a new study has found.
Dementia is currently the leading cause of death in Australia and Alzheimer’s disease is its most common form — accounting for more than 70% of cases.
Alzheimer’s is a progressive brain disease in which cognitive abilities gradually decline, leading to impaired memory and thinking skills.
However, some people maintain high levels of cognitive function even though their brains show early signs of the disease. Specifically, some older adults have Alzheimer’s‑related brain pathology, but no noticeable cognitive problems.
The study, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was a collaboration between Murdoch University and AdventHealth, and investigated why some people remain cognitively healthy despite early Alzheimer’s‑related brain changes.
“Our study looked at why some brains were more resilient than others, and whether factors such as peoples’ education, socioeconomic status and health of their brain made a difference,” said lead author Dr Kelsey Sewell, from Murdoch University’s School of Allied Health.
“Understanding these protective factors could help us develop earlier and more targeted strategies to minimise the effects of the disease on memory and thinking skills,” she said.
The research team analysed data from more than 600 older adults in the United States aged 65 to 80, who were living independently and had no signs of dementia or memory impairment.
They used blood tests and MRI scans to assess early Alzheimer’s‑related changes and overall brain health, examined life and social factors such as years of education, income, savings and financial security, and conducted cognitive tests measuring memory, attention, processing speed, working memory and executive function.
“Our main finding was that maintaining good overall brain health may help reduce the impact of Alzheimer’s‑related changes on cognitive function,” Dr Sewell said.
“We also observed early evidence that people with a higher socioeconomic status may be less affected by Alzheimer’s-related changes when it comes to memory, although more research is needed to confirm this relationship.”
Dr Sewell said the main takeaway for the public was to do everything you can to maintain a healthy brain.
“Things like exercise, maintaining a healthy diet, sleeping well, and finding new cognitive challenges can help to maintain a healthy brain. It is never too late, or too early to start,” she said .
“These results underscore the need for coordinated action across research, policy, and industry to design environments that support healthier choices and promote brain health at a population level.”
The data collection for this study was led by researchers at AdventHealth in Orlando, Florida.
The paper, Cognitive and Brain Reserve as Modifiers of Early Alzheimer Disease–Related Cognitive Vulnerability, was published in the journal Neurology.
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