Viral Myocarditis

In a potentially game-changing development, scientists have revealed a new understanding of sometimes fatal viral infections that affect the heart. Traditionally, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body's immune response to a viral infection. However, a new study sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in. In a potentially game-changing development, scientists with the Fralin Biomedical Research Institute at VTC have revealed a new understanding of sometimes fatal viral infections that affect the heart. Traditionally, the focus has been on heart inflammation known as myocarditis, which is often triggered by the body's immune response to a viral infection. However, a new study led by James Smyth, associate professor at the Fralin Biomedical Research Institute, sheds new light on this notion, revealing that the virus itself creates potentially dangerous conditions in the heart before inflammation sets in. The discovery, now online and set to appear in the March 29 issue of Circulation Research, suggests completely new directions to diagnose and treat viral infections affecting the heart. Given the high incidence of viral-related myocarditis leading to sudden cardiac death, the insight is crucial. Up to 42 percent of sudden cardiac deaths in young adults are attributed to myocarditis, and of these cases viral infection is the leading cause. "From a clinical perspective, our understanding of viral infection of the heart has focused on inflammation, causing problems with the rate or rhythm of the heartbeat," Smyth said. "But we have found an acute stage when the virus first infects the heart and before the body's immune response causes inflammation. So even before the tissue is inflamed, the heart is being set up for arrhythmia." To make this discovery, researchers focused on adenovirus, a common culprit in cardiac infection and myocarditis, using Mouse Adenovirus Type-3 to replicate the human infection process. They found that early in the infection, the virus disrupts critical components of the heart's communication and electrical systems. As a result, even before symptoms appear, the adenoviral infection creates conditions that disrupt the heart's gap junctions and ion channels, according to virologist Rachel Padget, the study's first author who worked in the Smyth lab while completing a doctoral degree from the Virginia Tech Translational Biology, Medicine, and Health graduate program. Gap junctions are like tiny tunnels between heart cells that allow them to communicate, and ion channels are like gates in the cell membranes that help maintain the right balance of ions needed for the heart to generate normal patterns of electrical activity that allow it to beat properly. When adenoviral infection disturbs these communication bridges and gatekeepers, it creates a situation where the heart might develop irregular patterns of electrical activity called arrhythmias affecting its mechanical beating and blood pumping capacity, and that can lead to sudden cardiac problems, especially in people with active infections. Now, by targeting specific heart changes induced by viral infections at the molecular level, researchers aim to reduce the risk of cardiac issues in people grappling with viral illnesses. "Individuals who have acute infections can look normal by MRI and echocardiography, but when we delved into the molecular level, we saw that something very dangerous could occur," Smyth said. "In terms of diagnostics, we can now work with our colleagues here to start looking ways to analyze blood for a biomarker of the more serious problem. People get cardiac infections all the time and they recover. But can we identify what's different about individuals that are at a higher risk to have the arrhythmia, possibly through a simple blood test in the doctor's office." The work was supported in part by grants from the National Institutes of Health, American Heart Association, Fralin Biomedical Research Institute Seale Innovation Fund and Lyerly Postdoctoral Excellence Award.

New high-resolution, whole transcriptome spatial mapping kit facilitates a more complete, unbiased view of larger tissue sections PALO ALTO, Calif.--(BUSINESS WIRE)-- Curio Bioscience today announced an expansion of its Curio Seeker product line with a larger format to deliver a more complete view of large biological structures, including human tissue samples, providing one hundred times more data compared to other whole transcriptome spatial analysis solutions. “The new Curio Seeker 10x10 spatial mapping kit enables spatial transcriptomic analysis of tissue up to one square centimeter. This larger format will facilitate studies with human tissue samples and whole-organ samples from model organisms, all in an easy-to-use workflow and industry-leading spatial resolution,” said Christina Fan, PhD, Co-founder and CTO of Curio Bioscience. “Together with the 3x3 spatial mapping kit launched earlier this year, the expanded Curio Seeker product line will help accelerate scientific discovery and advance basic research by lowering the barrier of entry to complex spatial analyses while providing high quality data.” Curio Seeker is a whole transcriptome analysis reagent kit solution that provides the ability to generate molecular images of tissue sections by capturing and mapping the spatial location of RNA molecules using next-generation sequencers. The spatial transcriptomic data generated by Curio Seeker enable researchers to better understand cellular functions in the context of their native environment, providing additional biological insight that are not available from single-cell RNA sequencing approaches. Among the company’s rapidly growing list of early adopters is Cornell University where researchers are using the Curio Seeker 10x10 kit to access high-resolution transcriptomics information in their organisms of interest. Professor Iwijn De Vlaminck’s lab has applied spatially resolved transcriptomics with the Curio Seeker kit to study the pathogenesis of viral myocarditis and viral encephalitis, the development of the chicken heart, and the cellular and molecular processes associated with ovulation. “High-resolution, spatially resolved RNA sequencing is a new and powerful approach to map and study biology. A highly useful tool to unlock the real potential of this new approach is the new Curio Seeker 10x10 kit, which allows us to use our existing sequencer to generate more unbiased, high-resolution spatial transcriptomics data across larger tissue sections than we could have achieved any other way,” said Iwijn De Vlaminck, associate professor of biomedical engineering at Cornell University. “We are extremely excited about the data being generated from the Curio Seeker kit, and we are already gaining compelling new insights into the spatial relationships between cells and cell neighborhoods in our model system.” The Curio Seeker kit provides a reliable baseline for understanding developmental biology, assessing the immunological response to cancer, and discovering molecular signatures that predict disease progression or treatment response among other studies. The new 10x10 kit joins the Curio Seeker 3x3 kit, which was the first in a suite of products designed to accelerate high-resolution spatial discovery using existing sequencing instrumentation. With industry-leading cellular scale resolution, the new kit enables scientists to get the most transcriptomic data from their samples. It is compatible with all Illumina sequencers, allowing for plug-and-play use of the kit in existing sequencing workflows without requiring any additional equipment. Curio Bioscience leveraged the Slide-seq technique that its academic co-founders developed at the Broad Institute of MIT and Harvard. The academic co-founders are Evan Macosko, MD, PhD, associate professor of psychiatry at Massachusetts General Hospital; Fei Chen, PhD, assistant professor at Harvard University’s Department of Stem Cell and Regenerative Biology; and Samuel Rodriques, PhD, group leader at the Francis Crick Institute. “The number of data points that Curio Seeker 10x10 kit delivers is significantly greater than what was generated with the original Slide-seq technique. It brings high resolution, whole transcriptome, spatial biology further into the scale of human biology, expanding a researcher’s ability to see larger regions of interest in a tissue sample,” said Fei Chen. “Curio Bioscience has taken an innovation and successfully scaled it with a commercial-grade solution that is simple to use and offers significantly better sensitivity. This evolution of our foundational technology will certainly help accelerate the impact of spatial transcriptomics in the scientific community.” For more information about the Curio Seeker family of kits, click here. About Curio Bioscience Curio Bioscience is advancing a new generation of high-precision tools for the life sciences industry. The company has developed innovative spatial biology capabilities to map the whole transcriptome at high resolution using existing sequencing workflows and instrumentation. The founding team has a strong track record of bringing genomic solutions to market. Based in Palo Alto, California, Curio Bioscience is a privately held company. For more information, visit .

MONDAY, July 10, 2023 (American Heart Association News) -- Last December, during the week before winter break, Abbie Hauler caught the flu. She had a deep cough and began complaining of chest pain. Her mother, Angie Hauler, told her to stay home and rest. But the eighth grader had tests to take before vacation started. And she didn't want to miss a weekend trip to celebrate the holidays with her father's family. "Teens can be stubborn," Angie said. "But on the way home that night, she called me and said, 'Mom, I really don't feel good.'" The next morning, Abbie complained that it hurt to breathe. Her mother took her to an urgent care clinic in suburban Columbus, Ohio, where she tested negative for COVID-19, but positive for influenza A. The doctor said her heart and lungs sounded fine and told her to rest and drink lots of fluids. The pain in her chest, he said, was from coughing. Abbie didn't sleep all night. She felt hot, then cold. She complained repeatedly that her chest hurt. Abbie slept that night in bed with Angie, allowing Angie to better keep an eye on her. The next morning, Angie got up to take a shower. When she came back to the room to get dressed, Abbie was lying quietly on her side. Her mother called her name but got no response. "I rolled her over, and her eyes were half open," Angie said. Abbie wasn't breathing. Her mother called 911. An operator told her to put Abbie on the floor and begin chest compressions. At the hospital, doctors said Abbie had a blood clot in her heart. The medical team worked on her for 90 minutes but couldn't revive her. Later, the medical examiner told the family she died from viral myocarditis, an inflammation of the heart muscle, brought on by the flu. Influenza myocarditis is rare and difficult to diagnose. It weakens the heart, preventing the body from getting enough blood. It also can cause blood clots to form in the heart, triggering a heart attack. Heart complications are the second most common cause of deaths related to the flu, which is estimated to kill tens of thousands of people in the U.S. each year. Viruses are the most common cause of myocarditis, accounting for up to 70% of all cases. Angie knew none of this when Abbie was ill. She certainly never thought the flu could be fatal to a 14-year-old. "People get the flu all the time," she said. "It's mind-boggling. If I had known, I would have rushed her to the hospital." Losing her child this way "has changed me as a person," Angie said, "and I don't want anybody else to have to go through this." Angie and her mother, Cathi Bell, want others to know about viral myocarditis so they can spot the symptoms and ask their health care professionals to test for it if a child complains of chest pain. Myocarditis in young people also has been associated with COVID-19 and some COVID-19 vaccinations, though studies have found cases are rare and tend to be mild. The symptoms of myocarditis include fatigue, shortness of breath, fever, chest pain, an irregular heartbeat, lightheadedness, and flu-like symptoms such as headaches, body aches, joint pain or sore throat. It can be diagnosed using blood tests, MRIs, chest X-rays and heart tests such as echocardiograms. Bell said since Abbie has died, she has spoken with others who lost young people to viral myocarditis. She doesn't understand how a child can be so healthy one day and gone the next. She misses frequent visits from her granddaughter. Abbie would sit on the floor playing Uno with her older sister, Sarah, and her grandfather. She'd sometimes stay for dinner and spend the night, often teasing her grandfather about his lack of tech-savvy skills. She'd laugh and try to teach him to use social media. "God, she loved to laugh," Bell said. Abbie was the kind of teenager who cracked jokes with her classmates and loved to pull pranks. She was also kind. She befriended new students and stood up to bullies at school. She was fiercely protective of her three younger siblings, especially her sister, Charli, who has autism. Now it's Abbie's friends and family who are protective of her. As a way of keeping her present for the milestones she would miss, Angie had Abbie cremated and put some of the ashes into a teddy bear. She dressed the bear like Abbie, putting her earrings into its ears and piercing its nose with her nose ring. At major class events, like a school award ceremony, a friend's baptism, softball games and the end-of-year clap-out for graduating students, Abbie's best friend, Baleigh, made sure to bring "Abbie Bear." "This way she could still be a part of those experiences," Angie said. "It's a way of keeping her with us." American Heart Association News covers heart and brain health. Not all views expressed in this story reflect the official position of the American Heart Association. Copyright is owned or held by the American Heart Association, Inc., and all rights are reserved. By Laura Williamson, American Heart Association News Posted July 2023