NewsMakers
Slower clearance of coronavirus infection may explain why men fare worse than women
Why do men have trouble shaking off their infections? Seeking a molecular explanation, the researchers focused on how coronavirus infection occurs. To infect cells, coronaviruses must first latch onto well-known proteins, called ACE2 receptors, that sprout like tiny antennae from the surfaces of cells. Cell types expressing copious levels of ACE2 on their surfaces would theoretically be most susceptible to infection.
Researchers at Montefiore Health System and Albert Einstein College of Medicine may have solved a mystery surrounding the novel coronavirus pandemic: Why men infected by the virus generally show more severe symptoms and are more likely than women to die from COVID-19.
In collaboration with the Kasturba Hospital for Infectious Diseases in Mumbai, India, the scientists showed for the first time that men clear the virus from their bodies slower than women and found a possible explanation: a potential male-only “reservoir” for coronavirus.
Their study was uploaded to MedRxiv, a website created by Cold Spring Harbor Laboratory to make research quickly available to the scientific community before undergoing the usual peer review process. It has become widely used to share information quickly during the COVID-19 pandemic.
“COVID-19 studies worldwide have consistently shown a higher incidence and greater severity of the disease in men compared with women,” says Aditi Shastri, M.D., assistant professor of medicine at Einstein, a clinical oncologist at the Montefiore Einstein Center for Cancer Care, and lead author of the Montefiore-Einstein study. “Our collaborative study found that men have more difficulty clearing coronavirus following infection, which could explain their more serious problems with COVID-19 disease.”
The viral-clearance analysis involved 68 people (48 men and 20 women) with symptoms of COVID-19 who were examined at India’s Kasturba Hospital for Infectious Diseases, in Mumbai. After undergoing initial nasal swab tests indicating active infection, individuals were re-tested with serial swabs until the tests turned negative, indicating the time taken to clear the coronavirus. The women cleared the virus significantly earlier than men: a median of four days for women vs. six days for men.
Next, three Mumbai families were identified in which men and women had tested positive for coronavirus infection on swab testing. Again, the women in all three families cleared the coronavirus earlier than male members of the same family.
Why do men have trouble shaking off their infections? Seeking a molecular explanation, the researchers focused on how coronavirus infection occurs. To infect cells, coronaviruses must first latch onto well-known proteins, called ACE2 receptors, that sprout like tiny antennae from the surfaces of cells. Cell types expressing copious levels of ACE2 on their surfaces would theoretically be most susceptible to infection.
The researchers consulted three independent databases with information on ACE2 expression in different tissues. They saw that the testes, along with the lungs and kidneys, were among the areas of the body with the highest ACE2 expression. By contrast, ACE2 could not be detected in tissue of the ovaries, the female equivalent of the testes.
Dr. Shastri stresses that the novel coronavirus’ ability to infect and multiply in testicular tissue needs to be confirmed, but says it wouldn’t surprise her. A recent study from China compared the levels and ratios of sex hormones in male COVID-19 patients vs. healthy men of the same age. The results indicated that the COVID-19 patients had experienced impaired testicular function—evidence that the testes may be significantly affected when men develop COVID-19. Such a COVID-19 complication could have important medical and public health implications, she notes, and deserves to be investigated by clinical trials.
The study’s Montefiore-Einstein senior authors are Amit Verma, M.B.B.S., professor of medicine and of developmental & molecular biology at Einstein and director of hematologic malignancies at Montefiore; and Ulrich Steidl, M.D., Ph.D., professor of cell biology and of medicine and the Diane and Arthur B. Belfer Faculty Scholar in Cancer Research at Einstein, and associate chair for translational research in oncology at Montefiore.
The study’s other senior author is Jayanthi Shastri, M.D., a microbiologist and infectious disease specialist. As director of Kasturba Hospital’s molecular diagnostic laboratory, Dr. Jayanthi Shastri led Mumbai’s effort to serially monitor and analyze coronavirus infection in individuals and their family members.
NewsMakers
Scheduling dental care during prenatal visits boosts oral health care during pregnancy
Scheduling a dental appointment during prenatal clinic visits—a simple, no-cost task that doesn’t require extra staff—increases the likelihood that patients later see a dentist during pregnancy.
Prenatal visits might include bloodwork, discussions of due dates and vitamins, and ultrasounds. What if these visits could also improve oral health care among pregnant patients?
New research shows that scheduling a dental appointment during prenatal clinic visits—a simple, no-cost task that doesn’t require extra staff—increases the likelihood that patients later see a dentist during pregnancy.
The study, published in the American Journal of Public Health, demonstrates the benefit of coordination among health providers and integrating oral health into prenatal care, especially for vulnerable patient populations.
Historically, dentists avoided treating women during pregnancy unless it was an emergency, or only provided care during the second trimester. This guidance changed once studies showed that routine and emergency dental care is safe during pregnancy—and current obstetric and dental guidelines stress that dental care can and should be provided during this critical period.
Moreover, pregnancy increases the risk of some oral health conditions, including gum inflammation and sometimes tooth decay, making routine dental care even more important during pregnancy. Some oral health issues may affect the fetus or even be transmissible to the child after birth.
Marginalized groups, including low-income individuals and those insured by Medicaid, are known to have higher rates of dental disease. Yet women enrolled in Medicaid are far less likely to see a dentist for a cleaning during pregnancy compared to women with private insurance.
“Many of those vulnerable to oral disease enter pregnancy with dental disease, and this may worsen during pregnancy,” said study author Stefanie Russell, associate professor at Rutgers School of Dental Medicine and an adjunct associate professor at NYU College of Dentistry, who led this research while at NYU.
One way to try and increase dental care among pregnant women is to reach them where they already are: their prenatal appointments. To bridge this gap, researchers and clinicians at NYU College of Dentistry teamed up with neighboring NYC Health + Hospitals/Bellevue, the oldest public hospital in the US, to create the New York University/Bellevue Prenatal Oral Health Program.
During weekly sessions at Bellevue’s prenatal clinic, pregnant patients receive a standardized screening to assess their oral health. Those with dental needs are referred to NYU College of Dentistry for follow-up care, educated about the importance and safety of dental care during pregnancy, and informed that Medicaid covers dental care in New York.
From 2018 to 2020, 420 prenatal patients with Medicaid coverage were referred to NYU Dentistry for follow-up dental care; the majority were Hispanic, and roughly half spoke Spanish as their first language. Referrals for dental care took two forms: immediately scheduled dental appointments made before the patient left the prenatal clinic or through a patient navigator. The patient navigator—a bilingual professional—educated patients regarding oral health, reminded patients of their upcoming dental appointments, and followed up after to identify any issues.
Nearly 44 percent of patients referred to NYU College of Dentistry followed through with a dental appointment. Both immediate appointment scheduling and the patient navigator increased the chances of a patient receiving dental care, but those who had appointments scheduled at their prenatal visit were 2.6 times more likely to see a dentist than those without appointments scheduled—even more likely than those who worked with the patient navigator.
“This suggests that immediately scheduled dental appointments can be an effective way to increase dental care utilization during pregnancy, without needing to hire extra staff,” said study author Shulamite Huang, assistant professor of epidemiology and health promotion at NYU College of Dentistry.
The authors conclude that integrating oral health screening in a prenatal clinic is feasible and increases engagement with dental care during pregnancy. They are continuing their research to measure whether this care improves oral health outcomes and to better understand how dental screening can be successfully integrated with prenatal care in other settings.
“A warm hand-off is key for addressing part of the barriers to dental care during pregnancy. Our team plans to further investigate and optimize interventions addressing both patient-, provider-, and healthcare system-level barriers to dental care during pregnancy,” said Huang.
Additional study authors include Richard Heyman and Mary Kang of NYU Dentistry; Belkys Saba, formerly of NYU Dentistry; Chloe Bird of the Tufts University School of Medicine; and Chengwu Yang of the Florida Atlantic University Schmidt College of Medicine.
NewsMakers
Why a UTI hurts — and why that might be a good thing
Australian researchers have discovered a previously overlooked group of bladder nerves that help detect urinary tract infections (UTIs) and trigger the body’s response to clear them, providing a potential new target for future bladder pain therapies.
Australian researchers have discovered a previously overlooked group of bladder nerves that help detect urinary tract infections (UTIs) and trigger the body’s response to clear them, providing a potential new target for future bladder pain therapies.
The study shows that bladder nerves located close to the lining of the bladder act as a frontline infection sensor, helping the body recognise UTIs and trigger responses that reduce the severity and spread of infection.
UTIs are among the most common bacterial infections worldwide, with more than 400 million cases reported every year. Nearly one in three women will experience UTIs before the age of 24, and many elderly people and those with bladder issues from spinal cord injuries can experience multiple UTIs in a single year.
Symptoms often include frequent urination, a sudden urge to urinate, pain during urination, and pelvic discomfort can be debilitating for some patients.
Flinders University’s Dr Luke Grundy says that while scientists have long understood how the bladder senses as it fills and triggers urination, the role of a specialised group of bladder nerves near the bladder lining has remained unclear.
“Most bladder nerves act like a fuel gauge, telling the brain when the bladder is filling up and needs emptying,” says Dr Grundy, Head of the NeuroUrology Research Group at Flinders University.
“The nerves we studied in this research are different. They sit close to the bladder lining and appear to act more like an early warning system, detecting infection and inflammation.
“They don’t just sense infection. They help coordinate the body’s response to it by triggering pain and urinary frequency, behaviours that appear to help clear bacteria from the bladder as part of the body’s defence system.”
Lead author and recently graduated PhD student Dr Cindy Tay says the discovery changes how these nerves are understood.
“These mucosal nerves have puzzled scientists for almost two decades because they stay quiet while the bladder fills and empties, which is the main job of the bladder,” says Dr Tay.
“What we’ve found is that they have a hidden job — acting as an early warning system that springs into action the moment infection takes hold.”
The research team developed a novel method to selectively study a specialised group of sensory nerves in the bladder lining of mice, revealing that while these nerves play little role in normal bladder function, they become highly responsive during a UTI and help detect and respond to infection.
“When the bladder is healthy, these nerves are relatively quiet, but during a urinary tract infection they become highly sensitive and respond to the presence of bacteria and inflammation,” says Dr Grundy.
“It may feel unpleasant, but urinating more frequently actually helps clear the infection by flushing out the harmful bacteria.”
The study also helps explain why people with conditions affecting nerve function may be more prone to recurrent or severe UTIs.
“If the nerves that detect infection aren’t working properly, the body may not respond as effectively,” says Dr Grundy.
Building on previous research, the new study reveals a deeper understanding of how UTIs affect bladder function and the nervous system, and could help develop new treatments that target these nerves to relieve UTI-related symptoms.
“Our findings provide new insight into how the bladder detects and responds to infection, helping explain the biological processes that drive the pain, urgency and discomfort commonly experienced during UTIs,” says Dr Grundy
Researchers say the next challenge is to develop therapies that ease the pain and urgency associated with UTIs while preserving the protective role these nerves play in fighting infection.
The paper, ‘Bladder mucosal afferents detect UTI and aid pathogen clearance,’ by Cindy Tay, Harman Sharma, Stewart Ramsay (University of Adelaide), Georgia Bourlotos, Sarah K Manning, Natalie E Stevens, Sophie J Miller, Geraint B Rogers, David J Lynn, Feargal J Ryan, Andrea M Harrington (University of Adelaide), Vladimir Zagorodnyuk, Steven L Taylor and Luke Grundy was published in Proceedings of the National Academy of Sciences (PNAS).
NewsMakers
Pregnancy complications can signal heart disease risk years before traditional screening, study finds
Some women, particularly younger women often considered low risk, may face a higher risk of heart disease earlier than previously recognized.
McGill University researchers have developed a new tool to identify heart disease risk in women earlier in life.
Findings from a study published in JACC: Advances highlight gaps in existing approaches.
“Heart disease is the leading cause of death in women, yet existing risk tools were developed in older populations and ignore factors unique to women,” said senior author Robert Platt, Professor in the Department of Epidemiology, Biostatistics, and Occupational Health and Director of the School of Population and Global Health.
While pregnancy complications are known to be linked to future heart risk, there has been no way to identify which younger women are most at risk, he added.
Detecting risk earlier
Using health data from more than 260,000 women in the UK aged 15 to 45 who had given birth, researchers developed and validated a prediction model to estimate future heart disease risk. Participants were followed for nearly four years after delivery.
The model identified several factors – not included in existing tools – that can help predict risk, including hypertensive disorders of pregnancy, gestational diabetes, preterm birth, PCOS, depression, thyroid disorders, oral contraceptive use and social deprivation.
The findings suggest some women, particularly younger women often considered low risk, may face a higher risk of heart disease earlier than previously recognized.
“Millions of women who give birth each year are never considered candidates for cardiovascular risk assessment simply because of their age,” said co-author Kristian Filion, Professor in the Departments of Medicine and of Epidemiology, Biostatistics, and Occupational Health.
If integrated into routine postpartum care, this tool could enable earlier monitoring, lifestyle counselling or referral to a specialist, potentially helping prevent a heart attack or stroke later in life, he added.
The next step is to validate the model in Canada and the United States. In the longer term, the goal is to integrate a practical calculator into electronic health records so higher-risk patients can be identified earlier.
About the study
“Development and Validation of a Prediction Model for Cardiovascular Risk in Reproductive-Aged Women” by Sonia Grandi, Kristian Filion, Jennifer Hutcheon, Graeme Smith, and Robert Platt was published in JACC: Advances. The study was supported by the Canadian Institutes of Health Research.
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