Publisher Health

The emergence of new SARS-CoV-2 variants that can spread rapidly and undermine vaccine-induced immunity threatens the end of the COVID-19 pandemic. The delta variant (B.1.617.2) emerged in India and subsequently spread globally within a short time period. Also in Germany, almost all recent infections are due to this variant. In addition to Delta, so-called Delta Plus sub-variants have been observed, which carry additional mutations that may make them more dangerous.
A research team led by Stefan Pöhlmann and Markus Hoffmann from the German Primate Center — Leibniz Institute for Primate Research in Göttingen and colleagues from the Hannover Medical School, the University of Göttingen Medical Center and the Friedrich-Alexander University of Erlangen-Nürnberg have investigated why the Delta variant spreads so efficiently and whether Delta Plus viruses are more dangerous. They were able to show that Delta and Delta Plus infect lung cells with higher efficiency than the original virus.
In addition, one of four antibodies used to treat COVID-19 was not effective against Delta, and Delta Plus was even resistant against two therapeutic antibodies. Similarly, antibodies generated upon vaccination with the BioNTech-Pfizer and Oxford-AstraZeneca vaccines were also less effective against Delta and Delta Plus compared to the original virus. Delta and Delta Plus, on the other hand, were comparably inhibited, suggesting that Delta Plus may not pose a greater risk to vaccinated persons than Delta. Finally, it was found that individuals vaccinated first with Oxford-AstraZeneca and then with BioNTech-Pfizer had significantly more antibodies that inhibited Delta than individuals vaccinated twice with Oxford-AstraZeneca. The combination of two vaccines may thus induce a particularly strong immune protection against SARS-CoV-2 variants (The Lancet, Cell Reports, Cell Mol Immunol).
At present, more than 99 percent of SARS coronavirus 2 infections caused in Germany are due to the Delta variant, according to the Robert Koch Institute. Using cell culture experiments, a team of researchers led by Stefan Pöhlmann and Markus Hoffmann was able to show that Delta is better at entering lung cells compared to the original virus (the virus that circulated during the early phase of the pandemic). In addition, Delta is better at fusing infected lung cells with uninfected cells. “It is conceivable that by fusing cells in the respiratory tract, the Delta variant may spread more efficiently and induce more damage. This could contribute to a more severe course of COVID-19,” assumes Arora Prerna, scientist at the German Primate Center and first author of two studies specifically focusing on the Delta and Delta Plus variants.
Monoclonal antibodies are used to treat COVID-19. These antibodies are proteins that are produced by genetic engineering. Unlike our immune system, which produces a large number of different antibodies against pathogens during infection, only individual antibodies or combinations of them are used for COVID-19 therapy. The team led by Stefan Pöhlmann and Markus Hoffmann studied four of these antibodies. They found that Delta is resistant against the antibody bamlanivimab, while Delta Plus is resistant against two antibodies, bamlanivimab and etesevimab, which are used in combination for treatment of COVID-19 patients.
Delta and Delta Plus were less well inhibited (neutralized) by antibodies from infected and vaccinated individuals as compared to the original virus and this likely contributed to the rapid spread of Delta. A direct comparison of Delta and Delta Plus showed that both viruses were comparably neutralized. “This means that vaccination likely confers comparable protection against Delta and Delta Plus, and that Delta Plus is not significantly more dangerous than Delta,” says Stefan Pöhlmann. BioNTech-Pfizer’s vaccine is the most widely used vaccine in Europe, followed by Oxford-AstraZeneca’s vaccine. Due to very rare side effects following vaccination with Oxford-AstraZeneca, it is recommended in Germany and other countries that BioNTech-Pfizer is used for the second vaccination shot in people who have already received a first shot with Oxford-AstraZeneca. This strategy is referred to as heterologous vaccination. “Our studies show that heterologous vaccination induces significantly more neutralizing antibodies to Delta than two vaccination shots with Oxford-AstraZeneca. Individuals who have received such a heterologous vaccination may have a very good immune protection against Delta and Delta Plus,” says Markus Hoffmann.
“Our results are consistent with the observation that vaccination efficiently protects against development of severe disease after infection with the Delta variant, but frequently fails to completely suppress infection. In light of the efficient protection against severe disease, the goal continues to be a high vaccination rate. This can prevent the health care system from being overwhelmed in case of increased spread of Delta and closely related viruses during the winter months,” says Stefan Pöhlmann.
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Materials provided by Deutsches Primatenzentrum (DPZ)/German Primate Center. Note: Content may be edited for style and length.

If you have heart disease or risk factors for heart disease, you already know about the increased risk of heart attack and stroke. But did you know that coming down with the flu can substantially increase the risk of a serious or even fatal cardiac event? Or that getting the influenza vaccine can substantially reduce that risk, even if you do wind up contracting the seasonal virus?
Probably not, if annual influenza vaccination rates are any indication, especially if you’re under the age of 65. According to a Houston Methodist review published in the Journal of the American Heart Association, Americans with heart disease continue to have low vaccination rates every year despite higher rates of death and complications from influenza.
The flu vaccination rate for American adults who are less than 65 years of age and have heart disease is less than 50%, compared to 80% in older adults with heart disease.
“It seems that younger Americans with high-risk conditions have not gotten the same memo that their older counterparts have received about the importance of getting the influenza vaccine,” says Dr. Priyanka Bhugra, internal medicine specialist at Houston Methodist and lead author of the JAHA article. “That’s dangerous, considering people with heart conditions are particularly vulnerable to influenza-related heart complications, whether they’ve reached retirement age or not.”
It’s well-known that the flu can lead to significant respiratory symptoms such as pneumonia, bronchitis and bacterial infection of the lungs. The virus’ effects on the heart have historically been harder to parse out, in part because many patients already have a known predisposition to cardiac events and in part because the cardiac event often occurs weeks after the onset of the flu.
But here’s what recent research has shown: Cardiovascular deaths and influenza epidemics spike around the same time. Patients are six times more likely to experience a heart attack the week after influenza infection than they are at any point during the year prior or the year after the infection. In one study looking at 336,000 hospital admissions for flu, 11.5% experienced a serious cardiac event. Another study looking at 90,000 lab-confirmed influenza infections showed a strikingly similar rate of 11.7% experiencing an acute cardiovascular event. One in eight patients, or 12.5%, admitted to the hospital with influenza experienced a cardiovascular event, with 31% of those requiring intensive care and 7% dying as a result of the event, another study found.The reason influenza stresses the heart and vascular system so much has to do with the body’s inflammatory response to the infection.

Whether it’s reporting on conflicts abroad and political divisions at home, or covering the latest style trends and scientific developments, Times Video journalists provide a revealing and unforgettable view of the world.Whether it’s reporting on conflicts abroad and political divisions at home, or covering the latest style trends and scientific developments, Times Video journalists provide a revealing and unforgettable view of the world.

Intravenous immune globulin (IVIG) — a common treatment for multisystem inflammatory syndrome in children (MIS-C) — likely works by depleting immune cells called neutrophils, according to a recent study funded by the National Institutes of Health (NIH). MIS-C is a rare condition that usually affects school-age children who initially had only mild COVID-19 symptoms or no symptoms at all. The researchers also found that IVIG works in a similar manner for treating Kawasaki disease, another rare inflammatory condition that affects children and shares symptoms with MIS-C. The findings are published in the Journal of Clinical Investigation.
MIS-C is marked by severe inflammation of two or more parts of the body, including the heart, lungs, kidneys, brain, skin, eyes and gastrointestinal organs. Its symptoms overlap with Kawasaki disease, and treatments for MIS-C are guided in part by what is known about treating Kawasaki disease. IVIG, which is made up of antibodies purified from blood products, is a common and effective treatment for heart complications caused by Kawasaki disease. For MIS-C patients, however, IVIG alone does not always resolve symptoms, and healthcare providers may need to prescribe additional anti-inflammatory drugs.
To better understand how IVIG works and to improve treatments for children with MIS-C, researchers led by Ben A. Croker, Ph.D., and Jane C. Burns, M.D., from the University of California San Diego School of Medicine, profiled immune cells from patients with MIS-C or Kawasaki disease. The team sampled cells before treatment began as well as 2 to 6 weeks after patients received IVIG. The researchers found that neutrophils from these patients were highly activated and a major source of interleukin 1 beta (IL-1?), which is one driver of inflammation in the body. After IVIG treatment, these activated neutrophils were significantly depleted in patients with MIS-C or Kawasaki disease.
According to the study authors, their findings are the first to explain why IVIG is effective for both conditions. However, more work is needed to understand how IVIG causes cell death in these activated neutrophils and why certain patients with MIS-C require additional anti-inflammatory treatments. Overall, the research will help healthcare providers as they determine the most effective methods to treat patients with MIS-C.
The study is funded by NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Heart, Lung, and Blood Institute (NHLBI), and the National Institute of General Medical Sciences (NIGMS). The work is supported by NIH’s CARING for Children with COVID, PreVAIL kIds and RADxSM-rad research programs.

Autoimmune diseases — i.e. diseases where our own immune system damages the body — are growing, but we know little about what triggers them.
Researchers are now a step closer to finding an explanation. With the help of a new technique, researchers from Aarhus University have succeeded in identifying the particles in the blood that determine the development of autoimmune diseases. They have discovered that patients with the autoimmune disease Systemic Lupus Erythematosus (also called SLE or Lupus), form a previously unknown type of protein particle in the blood and that this particle is so large it finds its way into the vascular wall where it causes damage. The disease is potentially life-threatening and can e.g. cause blood clots and inflammation of the joints and organs.
Particles measured in nanometres
“We can see that the patients have an elevated proportion of the large particles in the blood. Because of their size, these are distributed right at the edge of the blood vessel, where they can potentially end up in the vessel wall and create inflammation,” explains Postdoc Kristian Juul-Madsen from the Department of Biomedicine at Aarhus University.
He is the lead author of a recently published study which describes how the researchers were able to utilise a new technique enabling them to follow specific protein particles in the patient’s blood sample and measure their size in nanometres. By doing this, it becomes clear that the scope and structure of the particles are crucial for the development of the disease.
“We connect the protein particles with small metal particles, which fluoresce strongly when illuminated by a laser. We can follow the process on a screen and this has led us to discover that the Lupus patients have a much higher concentration of the very large particles,” explains Kristian Juul-Madsen.

Researchers from the Okinawa Institute of Science and Technology Graduate University (OIST) have identified a protein that plays a key role in how the brain regulates appetite and metabolism. Loss of the protein, XRN1, from the forebrain, resulted in obese mice with an insatiable appetite, according to a new study published in the journal, iScience.
Obesity is a growing public health concern, with over 650 million adults worldwide designated as obese. The condition has been linked to many disorders, including cardiovascular disease, type 2 diabetes and cancer.
“Fundamentally, obesity is caused by an imbalance between food intake and energy expenditure,” said Dr. Akiko Yanagiya, a researcher in the Cell Signal Unit at OIST, headed by Professor Tadashi Yamamoto. “But we still understand very little about how appetite or metabolism is regulated by communication between the brain and parts of the body, such as the pancreas, liver and adipose tissues.”
In the study, the scientists created mice that were unable to produce the protein, XRN1, in a subset of neurons in the forebrain. This brain region includes the hypothalamus, an almond-sized structure that releases hormones into the body, helping to regulate body temperature, sleep, thirst and hunger.
At 6-weeks-old, the scientists noticed that the mice without XRN1 in the brain rapidly began to gain weight and became obese by 12 weeks of age. Fat accumulated in the mice’s body, including within adipose tissue and the liver.
When they monitored feeding behavior, the team found that the mice without XRN1 ate almost twice as much each day as the control mice.

Diagnoses for the disorder have soared in the past decade, driven in part by a loophole in regulations. A new study shows the impact has been more severe for Black Americans.The share of American nursing home residents who are recorded as having schizophrenia has soared over the past decade. As The New York Times reported last month, the change is driven in part by a surge of questionable diagnoses.A 2012 government effort to reduce unnecessary antipsychotic drug use in nursing homes included an exemption for residents with schizophrenia. Since then, the diagnoses have grown by 70 percent. Experts say some facilities are using the schizophrenia loophole to continue sedating dementia patients instead of providing the more costly, staff-intensive care that regulators are trying to promote.The impact of this has been more severe on Black residents, a new study in the Journal of the American Geriatrics Society has found. Since the new rules went into place, Black Americans with dementia have been 1.7 times as likely as their white nursing home neighbors to be diagnosed with schizophrenia, said Shekinah A. Fashaw-Walters, a public health researcher at the University of Minnesota and the study’s lead author.Black nursing home residents are already more likely to live in facilities that rank lower in numerous quality measures, she said, and now face higher health risks of being misdiagnosed as schizophrenic to justify antipsychotic prescriptions. For residents with Alzheimer’s disease and other forms of dementia, antipsychotic drugs increase the risk of infections and falls, and double the risk of death, studies have shown.“I wanted to look at that increase in schizophrenia by race to see if this policy had a differential effect,” she said.The findings align with past research on schizophrenia diagnoses. Among all age groups, clinicians are already more likely to misdiagnose a patient as schizophrenic — and more likely to prescribe antipsychotics — if they are Black, said Stephen Strakowski, vice dean of research at the Dell Medical School at the University of Texas at Austin.“When clinicians talk to a Black or white patient who look otherwise similar symptom-wise, they overemphasize psychotic symptoms, delusions and hallucinations, relative to other symptoms in Black patients compared to how they do with white patients,” he said.“So it wouldn’t be a terrible surprise that if you now incentivize the diagnosis, the difference will be magnified.”Experts have long been concerned about nursing home drugging. The National Partnership to Improve Dementia Care began in 2012 after years of research showed that antipsychotic medications were widely used in nursing homes despite warnings from the Food and Drug Administration about the potential harms. The partnership includes federal and state agencies, nursing homes, advocacy groups and caregivers. It supports caring for dementia patients without drugs. This approach often requires substantial staffing and additional training, whereas antipsychotic medications can make it easier for nurses and aides to handle difficult-to-care-for residents and costs less.The partnership called on state inspectors to look more closely at prescribing practices and to issue citations for unnecessary drug use. The prescription rates are counted in official statistics that the government uses to help rate facilities, a five-star system that serves as a consumer guide for families choosing a nursing home.On the surface, the partnership has had a significant impact, boasting a hefty reduction in the share of residents being given antipsychotic medications. But The Times’s report found that more than half of the officially reported reduction in drug use was attributable to the increase in schizophrenia diagnoses from the loophole in the new rules.Responding to The Times’s reporting last month, Catherine Howden, a spokeswoman for the Centers for Medicare and Medicaid Services, said: “It is unacceptable for a facility to inappropriately classify a resident’s diagnosis to improve their performance measures. We will continue to identify facilities which do so and hold them accountable.”Nursing homes have increasingly become a provider of last resort for the nation’s most vulnerable citizens, and some of the increase in prevalence of schizophrenia diagnoses could be driven by the movement of schizophrenia patients into nursing homes from other institutions.But many experts say the schizophrenia exception is a major factor. The exemption was created because antipsychotic medications are still considered the best treatment for many people with the disorder. But schizophrenia is almost always diagnosed at a young age, and the increase among older residents since the rule went into effect is hard to otherwise explain. When government investigators looked at the medical claims history of nursing home residents with schizophrenia diagnoses in 2018, they found that one in three had no history of treatment for the disorder.It wouldn’t be the first time that incentives had unintended consequences for nursing home behavior. One reason the drug rate grew so much in the first place, other researchers have found, was in reaction to an earlier government crackdown on the use of physical restraints.Research has repeatedly shown that Black Americans tend to receive less care, and often worse care, than white Americans across a range of health problems. Professor Fashaw-Walters says more attention is needed on how this plays out for older African Americans and other people of color. Too often, she said, policies are thought of as “colorblind” when in fact they might contribute to inequities.“There is such an increased risk with antipsychotics for all sorts of adverse outcomes, whether it’s falls or death,” she said. “This national partnership could be implicated in some of these adverse outcomes. That’s the kind of scary part that I think about the most.”

Scientists have worked out how to best get DNA to communicate with membranes in our body, paving the way for the creation of ‘mini biological computers’ in droplets that have potential uses in biosensing and mRNA vaccines.
UNSW’s Dr Matthew Baker and the University of Sydney’s Dr Shelley Wickham co-led the study, published recently in Nucleic Acids Research.
It discovered the best way to design and build DNA ‘nanostructures’ to effectively manipulate synthetic liposomes — tiny bubbles which have traditionally been used to deliver drugs for cancer and other diseases.
But by modifying the shape, porosity and reactivity of liposomes, there are far greater applications, such as building small molecular systems that sense their environment and respond to a signal to release a cargo, such as a drug molecule when it nears its target.
Lead author Dr Matt Baker from UNSW’s School of Biotechnology and Biomolecular Sciences says the study discovered how to build “little blocks” out of DNA and worked out how best to label these blocks with cholesterol to get them to stick to lipids, the main constituents of plant and animal cells.
“One major application of our study is biosensing: you could stick some droplets in a person or patient, as it moves through the body it records local environment, processes this and delivers a result so you can ‘read out’, the local environment,” Dr Baker says.

Although sometimes hard to accept, with aging, many things in our bodies change. One of these is the ability of the skin to regenerate. Old skin is just not as good as young skin at healing wounds. However, the molecular and cellular mechanisms underlying this are largely unknown. Now, researchers from Japan have identified a mechanism to explain why this happens and potentially how it can be fixed.
In a study published this month in the Journal of Cell Biology, researchers from Tokyo Medical and Dental University (TMDU) have revealed that the ability of skin stem cells to repair skin after an injury may be linked with their ability to move towards the injury.
Skin stem cells, also called keratinocyte stem cells, are responsible for skin regeneration and wound closure through a process called re-epithelialization. “Live-imaging and computer simulation experiments showed that human skin stem cells motility is coupled with their proliferative and regenerative capacity and old stem skin cells have a significantly reduced motility,” explains Daisuke Nanba, lead author of the study.
To understand the mechanisms behind this reduced motility in old stem cells, the researchers compared the wound healing and proliferative ability of skin stem cells derived from young mice (12 weeks old) and aged mice (19-25 months old). The experiments showed that a specific molecule, called EGFR (Epidermal Growth Factor Receptor), drives skin stem cell motility and that EGFR signalling is reduced in old stem cells. EGFR acts by preventing the degradation of a specific type of collagen, COL17A1, which is necessary to hold the layers of the skin together.
Interestingly, COL17A1 coordinates the movement of skin stem cells towards the injury by regulating actin and keratin filament networks in the cells. The researchers found that with age, a decrease in EGFR signalling occurs, leading to lower levels of COL17A1 and skin stem cells with reduced mobility that are less able to re-epithelialize the skin.
With advanced age, a reduced skin wound healing ability is associated with the development of so-called chronic nonhealing disorders, such as diabetic ulcers and pressure sores. “Although further investigations are still required, stabilizing COL17A1 by regulating its proteolysis is a promising therapeutic approach for improving the decline in skin regeneration observed with age that often leads to serious issues such as ulcers,” says Emi Nishimura, senior author on the study. This research sheds further light on the mechanisms underlying wound healing and may lead to the development of new therapeutic treatments to improve skin regenerative capacity.
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Materials provided by Tokyo Medical and Dental University. Note: Content may be edited for style and length.

University of Virginia School of Medicine researchers have revealed a vital but previously unknown role for immune cells that protect the brain from disease and injury: The cells, known as microglia, also help regulate blood flow and maintain the brain’s critical blood vessels.
In addition to revealing a new aspect of human biology, the findings may prove important in cognitive decline, dementia and stroke, among other conditions linked to diseases of the brain’s small vessels, the researchers say.
“Precise blood vessel function is critical to accommodate the extreme energy demands of the brain for normal brain function,” said UVA’s Ukpong B. Eyo, PhD, of UVA’s Department of Neuroscience, the UVA Brain Institute and UVA’s Center for Brain Immunology and Glia (BIG). “These findings suggest previously unknown roles for these brain cells in the proper maintenance of blood delivery to the brain and provide novel opportunities to intervene in contexts where blood perfusion to the brain is impaired.”
The Role of Microglia
Scientists have known that microglia play many important roles in the brain. For example, the cells police the natural blood-brain barrier that protects the organ from harmful germs in the bloodstream. Microglia also facilitate the formation of the brain’s complex network of blood vessels during development. And they are known to be important in many diseases. In Alzheimer’s disease, for example, recent work suggests that the loss of the immune cells is thought to increase harmful plaque buildup in the brain.
Scientists have been unsure, however, what role microglia play in maintaining blood vessels in a normal, healthy brain. The new research from Eyo and his colleagues reveals that the cells are critical support staff, tending the vessels and even regulating blood flow.
The UVA researchers identified microglia associating with the brain’s capillaries, determined what the immune cells do there and revealed what controls those interactions. Among the cells’ important responsibilities is helping to regulate the diameter of the capillaries and possibly restricting or increasing blood flow as needed.
“Researchers have been studying these cells in the living brain for over two decades but this is the first time we are able to get an idea of these mechanisms of microglia-blood vessel interaction,” said Eyo, a top expert on microglia. “It’s an exciting time to be the first to make these findings here at UVA.”
The researchers believe their new findings could have significant implications for diseases that affect the small vessels of the brain. These conditions are thought to contribute to strokes, Alzheimer’s, loss of balance and mental decline, among other serious health problems.
“We are currently expanding this research into an Alzheimer’s disease context in rodents to investigate whether the novel phenomenon is altered in mouse models of the disease and determine whether we could target the mechanisms we uncovered to improve known deficits in blood flow in such a mouse model of Alzheimer’s,” Eyo said. “Our hope is that these findings in the lab could translate into new therapies in the clinic that would improve outcomes for patients.”
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Materials provided by University of Virginia Health System. Note: Content may be edited for style and length.