RESEARCH EXPLORES HOW IMMUNE SYSTEM GETS ALTERED BY COVID-19 - The Daily Guardian
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RESEARCH EXPLORES HOW IMMUNE SYSTEM GETS ALTERED BY COVID-19

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Ludwig Maximilian University of Munich researchers say that COVID-19 reduces the numbers and functional competence of certain types of immune cells in the blood.

This could affect responses to secondary infections. The findings were published in the journal PLOS Pathogens. The SARS-CoV-2 coronavirus causes moderate to severe disease in 3-10 per cent of those infected. In such cases, the immune system overreacts to the virus, triggering an aberrant innate immune response that is characterized by systemic inflammation, intravascular blood clotting and damage to the cardiovascular system.

A team led by immunology professor Anne Krug at LMU’s Biomedical Center (BMC), which included many researchers based at the BMC and the LMU Medical Center, has carried out a comprehensive study of this phenomenon and uncovered hitherto unknown effects of the virus on the immune system.

In the journal PLOS Pathogens, they report that, following infection with SARS-CoV-2, the numbers of immune cells called dendritic cells in the circulation decline, while the functionality of the remaining fraction is impaired.

The authors believe that this could make patients more susceptible to secondary infections during, and immediately after recovery from a bout of COVID-19.

Dendritic cells (DCs) are responsible for initiating immune responses against invasive pathogens. They do so by activating helper T cells, which in turn stimulate B cells to secrete antibodies directed against the invader. Krug and her colleagues set out to determine the effects of moderate to severe coronavirus infection on this process. They analyzed blood samples obtained from 65 COVID-19 patients who had been treated at the LMU Medical Center.

They found that there were fewer DCs in these samples than in the blood of healthy controls. Furthermore, DCs isolated from the blood of patients showed a reduced ability to activate T cells.

“We had actually expected that DCs isolated from patients infected with SARS-CoV-2 would activate T cells more potently than DCs obtained from healthy donors,” says Krug.

“However, we discovered that, in the course of the disease, the proteins present on the surface of the DCs in patients’ blood were altered in a way that made them more likely to inhibit T cell responses.” In spite of this, by 15 days after diagnosis 90 per cent of these patients had generated antibodies directed against the SARS-CoV-2 spike protein, and many of them had also activated a T cell response. – these responses are the hallmarks of a robust immune reaction against the virus. “So, the drop in the numbers and reduced functionality of DCs does not seem to have a negative impact on the immune response to the coronavirus itself,” Krug says.

However, she is convinced that the reduced number and altered function of DCs is significant. It is conceivable that this might cause the immune system to react less strongly than expected to bacterial or other viral infections following recovery from COVID-19, but this possibility will require further clinical investigation.

What might account for the depletion of DCs in the blood and the decrease in their capacity to stimulate T cells? – Krug has several hypotheses to offer. It could in fact represent an appropriate regulatory process, she suggests. COVID-19 is often associated with vigorous inflammation reactions – so the phenomenon might be part of an attempt to downregulate inflammatory processes.

Dendritic cells might migrate from the blood into inflamed tissues, such as the lung, which could explain the fall in the numbers of DCs in the circulation. “However, we also found that the regeneration of dendritic cells is delayed,” Krug points out.

The authors of the study believe that this phenomenon could weaken the ability of patients to mount effective immune responses to other pathogens during, and in the immediate aftermath of asymptomatic COVID-19 infection. The team will now explore this issue further in an effort to determine whether the effects of SARS-CoV-2 on DCs play a role in long-term COVID.

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Bowel cancer patients at higher risk of clinical depression

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According to a new study, the prevalence of depression in bowel cancer patients is up to five years after surgery to treat their cancer.

The findings have been published in the ‘Colorectal Disease Journal’. A research team, led by the University of Southampton and funded by Macmillan Cancer Support, surveyed 872 adult patients with non-metastatic colorectal cancer before surgery and conducted follow-up surveys at regular intervals until 60 months post-surgery.

Lead author Dr Lynn Calman, Associate Professor in Nursing at the University of Southampton, said, “Depression in people living with colorectal cancer is an important clinical problem. Our study shows that the level of depression exceeds that of the general population over time. The research has also helped us to identify important time points where certain patients are at a high risk of depression which can inform strategies for recognition and referral for appropriate support.”

The results of the survey showed that before surgery over a fifth of participants (21 percent) reported clinically significant levels of depression, which reduced to 14 percent at 5 years. Risk factors identified before surgery that predicted subsequent depression were pre-existing clinically significant depression and anxiety, previous mental health service use, low confidence to manage illness-related problems, poor health, and low social support.

Further analysis of the findings suggested that people with bowel cancer who had reduced levels of social support are nearly 2.5 times more likely to also have depression. Among participants with the highest levels of social support at diagnosis, 16 percent developed clinical levels of depression within five years of their cancer treatment, compared with 37 percent of those with lower levels of social support.

While the above results are based on people’s experiences pre-Covid, evidence suggested the social isolation linked to the pandemic could be further worsening the mental health of people with cancer. The research team are currently carrying out another study into the impact of Covid-19, also funded by Macmillan Cancer Support; interim results from this have found that four in five (81 percent) cancer patients surveyed remained at home at all times in the pandemic, and nearly half (45 percent) of these have experienced at least two serious psychological impacts from the pandemic, such as feeling afraid, depressed or helpless.

Dany Bell, Strategic Advisor for Treatment, Medicines and Genomics at Macmillan Cancer Support said, “We know that for many people, being diagnosed with cancer and going through treatment is one of the scariest things they have ever faced, and this can often have a serious impact on people’s mental health.”

“Cancer affects people differently and at Macmillan, we’re here to ensure everyone living with cancer gets the support that’s right for them. We’re urging anyone in need of help – or simply someone to talk to – to get in touch with the trained nurses and advisors on our Support Line who are available at the end of the phone, seven days a week,” Bell added.

The new findings also showed that people with bowel cancer who had undergone neoadjuvant chemotherapy were also more likely to experience depression, perhaps explained by the fact these patients usually face more complex treatment, side effects and increased treatment time.

Dr Calman continued, “in this study, we investigated risk factors of depression at two key time points: close to diagnosis before surgery and two years after surgery, when routine oncological check-ups end.”

“Depression in people living with cancer can lead to poor health and wellbeing and this has an impact on long-term outcomes. Recognising those colorectal cancer patients who are at a higher risk and referring them to the right support services could therefore lead to overall improved outcomes for patients,” Calman concluded.

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THE SIGNIFICANCE OF MAINTAINING DENTAL HEALTH DURING DIABETES

Dr Gunita Singh

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Diabetes is the most common lifestyle disease in today’s world both in India and abroad in children and adults in men and women.

Diabetes is a disease that occurs when your blood glucose, also called blood sugar, is too high. Blood glucose is your main source of energy and comes from the food you eat. Insulin, a hormone made by the pancreas, helps glucose from food get into your cells to be used for energy. Sometimes your body doesn’t make enough—or any—insulin or doesn’t use insulin well. Glucose then stays in your blood and doesn’t reach your cells.

Over time, having too much glucose in your blood can cause health problems. Although diabetes has no cure, you can take steps to manage your diabetes and stay healthy. The most common types of diabetes are type 1, type 2, and gestational diabetes.

Too much glucose, also called sugar, in your blood from diabetes can cause pain, infection, and other problems in your mouth. Glucose is present in your saliva—the fluid in your mouth that makes it wet. When diabetes is not controlled, high glucose levels in your saliva help harmful bacteria grow.

These bacteria combine with food to form a soft, sticky film called plaque. Plaque also comes from eating foods that contain sugars or starches. Some types of plaque cause tooth decay or cavities. Other types of plaque cause gum disease and bad breath.

Gum disease can be more severe and take longer to heal if you have diabetes. In turn, having gum disease can make your blood glucose hard to control.

SOME COMMON PROBLEMS IN DIABETES

Tooth decay (cavities): Your mouth naturally contains many types of bacteria. When starches and sugars in foods and beverages interact with these bacteria, a sticky film known as plaque forms on your teeth. The acids in plaque attack the surfaces of your teeth (enamel and dentin). This can lead to cavities and gum disease. The higher your blood sugar level, the greater the supply of sugars and starches — and the more acid wears away at your teeth.

Early gum disease (gingivitis): Diabetes reduces your ability to fight bacteria. If you don’t remove plaque with regular brushing and flossing, it’ll harden under your gum line into a substance called tartar (dental calculus). The longer plaque and tartar remain on your teeth, the more they irritate the part of your gums around the base of your teeth, called the gingiva. In time, your gums become swollen and bleed easily. This is known as gingivitis.

Advanced gum disease (periodontitis): Left untreated, gingivitis can lead to a more serious infection called periodontitis, which destroys the soft tissue and bone that support your teeth. Eventually, periodontitis causes your gums and jawbone to pull away from your teeth, which in turn causes your teeth to loosen and possibly fall out. Periodontitis tends to be more severe among people who have diabetes because diabetes lowers the ability to resist infection and slows healing.

Thrush: People with diabetes may be more likely to develop thrush, which is a fungal infection caused by the yeast Candida albicans. Signs of thrush include painful white or red patches inside your mouth. Practicing good oral hygiene can help you avoid thrush.

Dry mouth (xerostomia): Some people with diabetes also experience a lack of saliva, a condition known as dry mouth. Without saliva to keep your mouth moist and bathe your teeth, you could be at risk of tooth decay, gum disease, and thrush.

It is important to take proper dental care to help prevent damage to your teeth and gums, and its very important to take diabetes and dental care seriously and there are some ways by following which you can take care of yourselves.

Make a commitment to manage your diabetes. Monitor your blood sugar level, and follow your doctor’s instructions for keeping your blood sugar level within your target range. The better you control your blood sugars, the less likely you are to develop gingivitis and other dental problems.

Brush your teeth at least twice a day. Brush in the morning, at night, and, ideally, after meals and snacks. Use a soft-bristled toothbrush and toothpaste that contains fluoride. Avoid vigorous or harsh scrubbing, which can irritate your gums.

Schedule regular dental visits. Visit your dentist at least twice a year for professional cleanings, X-rays, and checkups. Look for early signs of gum disease. Report any signs of gum disease — including redness, swelling, and bleeding gums — to your dentist. Also mention any other signs and symptoms, such as dry mouth, loose teeth, or mouth pain.

Smoking increases the risk of serious diabetes complications, including gum disease and ultimately, loss of your teeth. If you smoke, ask your doctor about options to help you quit.

The author is practising Cosmetic and Laser dental surgeon for 20 years. BDS MD Dental Lasers, Director Dentem & Associate Consultant Sir Ganga Ram Hospital.

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VIRAL EVOLUTION AMONG ANIMALS MIGHT REVEAL COVID-19’S FUTURE

The global reach and spillover of the virus has given researchers a unique opportunity to investigate the viral evolution of SARS-CoV-2.

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The findings of a new study suggest that when animals catch Covid-19 from humans, new SARS-CoV-2 variants can arise.

To evaluate this phenomenon, an interdisciplinary team at the College of Veterinary Medicine and Biomedical Sciences systematically analysed mutation types occurring in the virus after infection of cats, dogs, ferrets, and hamsters. The study was recently published in ‘PNAS’, the official journal of the National Academy of Sciences. Confirmed Covid-19 cases in a variety of wild, zoo, and household animals demonstrate cross-species transmission, which is a rare occurrence for most viruses.

“SARS-CoV-2, in the realm of coronaviruses, has a very broad species range,” said Laura Bashor, one of the first authors and a doctoral student in the Department of Microbiology, Immunology and Pathology. “Generally speaking, many types of viruses can’t infect other species of animals, they evolved to be very specific.”

“Humans have so much exposure to many different animals which permitted this virus to have the opportunity to expose a variety of different species,” said Erick Gagne, a first author and now an assistant professor of wildlife disease ecology at the University of Pennsylvania.

The global reach and spillover of the virus have given researchers a unique opportunity to investigate the viral evolution of SARS-CoV-2, including in University Distinguished Professor Sue VandeWoude’s laboratory at Colorado State University.

These specialists in disease transmission in wild and domestic cats applied their experience in sequence analysis and studying a collection of genomes to SARS-CoV-2. Researchers in the VandeWoude lab worked with Assistant Professor Angela Bosco-Lauth and Professor Dick Bowen in the Department of Biomedical Sciences, who used their animal modelling expertise to develop a test for SARS-CoV-2 susceptibility of animal species.

Also, the key to the findings was a newer sequencing technique of the virus at different stages of the study, now common to detect variants in the human population. Mark Stenglein, associate professor in the Department of Microbiology, Immunology, and Pathology, provided computational skills in analysing biological molecule sequences, known as bioinformatics, to the study.

“We found there was evolution, we saw the selection on the virus, and we saw a lot of variants emerge in the genome sequence of the virus,” said Bashor.

To provide ample viral material for the study, Bosco-Lauth and Bowen cultivated a SARS-CoV-2 human sample in cells grown in the lab. Bashor and Gagne determined that multiple mutations developed, and became a greater percentage of the genetic population, at each step of this process.

Then the virus was introduced to the four household species, and samples of the virus were collected from their nasal passages after infection. “In the animals, the cell culture variants reverted back to the initial human type, which indicates that likely there is adaption occurring in that cell culture and environment that was selected for those variants,” said Gagne.

Not all these mutations within the cell culture SARS-CoV-2 variant transferred in the new hosts. Instead, different mutations emerged within the virus shed by the live animals. The initial viral sample in the study was isolated in early 2020. The team observed mutations that have since formed widespread SARS-CoV-2 strains in the human population at an accelerated rate throughout the study.

“Among those were a number that we’ve since seen in humans in the alpha, beta, delta variants,” said Dr Sue VandeWoude, senior author. “There were specific genetic code changes that mimicked what other scientists have reported in people.”

Contact exposure between two cats demonstrated the SARS-CoV-2 variant can be transmitted with the possibility of producing a new strain within the species. “That’s what we’re seeing in people too,” said Bosco-Lauth. “Hosts that are really well adapted to support SARS-CoV-2 infection are also very good at allowing these mutations to stick and to be passed on.”

Bashor did not anticipate studying SARS-CoV-2 when she came to CSU to begin her doctoral studies during the pandemic. However, it provided a unique opportunity to hit the ground running as a graduate student on a “really cool and viable project” in disease ecology and evolution.

Gagne was completing his postdoctoral research on the cross-species transmission of feline retroviruses in the VandeWoude lab when the team launched the SARS-CoV-2 study. Now an assistant professor, he has continued to investigate SARS-CoV-2 spillover with the Wildlife Futures Program at the University of Pennsylvania.

Graduate students and early-career scientists like Bashor and Gagne, have made meaningful contributions to SARS-CoV-2 research, said Vande Woude. The team has continued their investigations to focus on cats, as they have shown higher susceptibility for Covid-19 spillover from humans and can produce variants of the virus and spread to other cats.

Bashor began analysing SARS-CoV-2 genome sequences from a large pool of cat species all over the world, including tigers, lions and snow leopards. The publicly available data of infected cats could provide additional insights on the adaptability and mutability of Covid-19 within and among cat species. There is no evidence of transmission from cats to humans. But cats continue to be susceptible to all variants of Covid-19 in the human population. By understanding viral evolution within cats, the research team may find answers to the question: what is the future of SARS-CoV-2 for humans and animals.

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Study finds cardiovascular disease, high cholesterol linked to plastics

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A new study has found that phthalate—a chemical used to make plastics more durable—has led to increased plasma cholesterol levels.

The findings of the study were published in the journal ‘Environmental Health Perspectives’. “We found dicyclohexyl phthalate, or DCHP, strongly binds to a receptor called pregnane X receptor, or PXR,” said Changcheng Zhou, who is a professor in the UCR School of Medicine.

“DCHP ‘turns on’ PXR in the gut, inducing the expression of key proteins required for cholesterol absorption and transport. Our experiments show that DCHP elicits high cholesterol by targeting intestinal PXR signalling,” added Zhou.

DCHP, a widely used phthalate plasticiser, has recently been proposed by the Environmental Protection Agency as a high-priority substance for risk evaluation. Not much is known yet about DCHP’s adverse effects on humans.

“To our knowledge, our study is the first to show the effects of DCHP exposure on high cholesterol and cardiovascular disease risk in mouse models. Our results provide insights and new understandings of the impact of plastic-associated chemicals on high cholesterol—or dyslipidemia—and cardiovascular disease risk,” Zhou said.

Zhou’s team also found that mice exposed to DCHP had in their intestines higher circulating “ceramides”—a class of waxy lipid molecules associated with increased cardiovascular disease risk in humans—in a way that was PXR-dependent.

“This, too, points to the potentially important role of PXR in contributing to the harmful effects of plastic-associated chemicals on cardiovascular health in humans,” Zhou said.

Zhou was joined in the research by Zhaojie Meng, Jinwei Liu, Rebecca Hernandez, and Miko Gonzales of UCR; and Yipeng Sui, Taesik Gwag, and Andrew J. Morris of the University of Kentucky.

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DEMENTIA CREATES LISTENING ISSUES IN QUIET, NOISY ENVIRONMENTS

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Listening to the spoken word in noisy environments is challenging for everyone. Acoustic studies show people with mild dementia struggle to understand speech in both noisy and quiet environments, highlighting the need for everyone to communicate clearly.

During the 181st Meeting of the Acoustical Society of America, Kate McClannahan, from Washington University School of Medicine, discussed how background noise impacts have spoken word recognition in people with mild dementia. The talk, “The effect of mild dementia on speech perception in quiet and noise,” took place on Wednesday, December 1, at the Hyatt Regency Seattle.

Difficulty in understanding speech, especially in background noise, is a common concern for older adults. Using a word identification task in quiet and noisy conditions, researchers examined the impact of mild dementia on speech perception. They tested individuals with and without mild dementia.

The scientists found word identification scores of those without dementia were significantly better in all conditions, meaning people with mild dementia symptoms recalled fewer words in both quiet and noisy situations.

In the quiet condition, the group with mild dementia missed around 20 per cent of the words, while the control group missed approximately 5 per cent. The findings indicate individuals with mild dementia struggle with understanding speech, even without background noise.

“What is important to take away from this study is that people who are experiencing mild dementia symptoms may have difficulty understanding speech in both quiet and acoustically challenging situations,” said McClannahan.

McClannahan added, “Therefore, when conversing with someone who may be experiencing cognitive difficulties, considerations such as speaking more clearly and slowly, reducing background noise and distractions, making sure the listener can see the speaker’s face and providing ample contextual information, may help to improve the listener’s speech understanding.”

“If you or a loved one notice difficulty with your communication, seeking the advice and care of an audiologist is a great place to start!” McClannahan said taking these measures will aid effective communication for all listeners.

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Study provides model for treating HIV/AIDS, depression

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For people with HIV who are also struggling with depression, remaining healthy is often an insurmountable challenge, especially in South Africa, home to the highest number of cases in the world and a significant shortage of mental health professionals.

However, a new study has provided local and global implications for successfully treating both mental health and HIV/AIDS in settings like South Africa—or even Miami, the epicentre of new cases in the United States. The findings of the study were published in the ‘Journal of the International AIDS Society’.

In the study, an international team of researchers—led by the University of Miami’s Steven Safren and two colleagues—demonstrated the effectiveness of training nurses in public HIV clinics to deliver a specially adapted cognitive behaviour therapy (CBT) to help people with depression and uncontrolled HIV adhere to their prescribed medication regiment. CBT is a proven approach for changing faulty or unhelpful thinking or behavioural patterns.

“We know that treating HIV-positive people who are clinically depressed with antidepressants alone does not affect their viral loads. Their depression may improve, but their adherence does not,” said Safren, professor of psychology and director of the University’s Center for HIV/AIDS Research and Mental Health.

“So, given the global shortage of mental health professionals, we showed it is possible to train nurses to deliver cognitive-behavioural therapy for adherence and depression (CBT-AD), an intervention that successfully addresses both clinical depression and uncontrolled HIV,” added Safren.

Safren, who joined the University in 2015 from Harvard Medical School, conducted the study in a poor township just outside of Cape Town, South Africa, with fellow researchers John A Joska, director of the HIV Mental Health Research Unit and professor of psychiatry at the University of Cape Town, and Conall O’Cleirigh, associate professor of psychology at Harvard and director of Behavioral Medicine at Massachusetts General Hospital.

For their study, the researchers recruited 161 patients with uncontrolled HIV/AIDS and clinical depression from four public health clinics in the township of Khayelitsha. Although a medical officer could prescribe antidepressants to the patients, the clinics have limited psychological services—as does the country in general. According to the study, South Africa only has 0.28 psychiatrists and 0.32 psychologists per 100,000 people.

At the onset of the study, all participants received the usual enhanced care for clinically depressed HIV-AIDS patients who did not achieve viral suppression after receiving the first month of their antiretroviral medication. That customary treatment included another prescription and follow-up meetings with an adherence counsellor.

But half the patients were also randomly assigned to attend eight CBT-AD sessions, where specially trained nurses integrated strategies for treating depression with adherence counselling that included modules on life skills, depression, relaxation, mood monitoring, and problem-solving.

The idea, Safren said, was to help patients “turn down the volume” of their mental health symptoms, so they would be more open to counselling on the benefit of taking their medication. To track their adherence, the patients also received an electronic pillbox that, every time it was opened, transmitted a real-time signal to a web server.

And, researchers found, the task-shared approach delivered by nurses proved effective. Patients who completed the CBT-AD sessions were more than 2.5 times more likely to achieve undetectable viral loads than those who underwent the usual care.

Now, Safren noted, the next step will be for the research team to evaluate how to sustainably implement the CBT-AD approach in South Africa or even South Florida. He said the task-shared approach could be viable in Miami, where there are fewer services to help people achieve viral suppression than in other US cities with large populations of people living with the virus.

“South Africa has the most cases of HIV/AIDS in the world and Miami is the city with the highest incidence of new cases in the US—so there is a parallel,” Safren pointed out.

“And unlike places like New York or Massachusetts, where people are more likely to be virally suppressed, Florida doesn’t have the same public health resources. If, for example, you’re an HIV patient at Massachusetts General or Fenway Health, where I used to work, and you miss your visit, or your viral load becomes uncontrolled, social workers will swoop in and provide assistance. That doesn’t happen as often in Florida and other places in the US with less public health HIV/AIDS funding,” Safren added.

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