Gamechanger: New way to improve outcomes in kids with eosinophilic esophagitis

A groundbreaking study from Ann & Robert H. Lurie Children’s Hospital of Chicago determined the threshold for a new measure of early scarring in the esophagus of children with eosinophilic esophagitis (EoE), which allows immediate intervention during endoscopy to halt further damage and prevent food from getting stuck in the esophagus (feeding tube) of kids with this condition. Findings were published in the journal Clinical Gastroenterology and Hepatology, and were supported by the Campaign Urging Research for Eosinophilic Diseases (CURED) Foundation.
EoE is a chronic immune-mediated disorder of the esophagus that affects adults and children with a prevalence of 0.5 to 1 per 1000. Left untreated, chronic inflammation promotes scarring of the esophagus, and the development of esophageal rings and stricture, which interferes with passage of solid food and can cause impaction (when food is stuck in the esophagus and cannot dislodge).
Endoscopic Functional Luminal Impedance Probe (EndoFLIP) was used in the study to measure the “distensibility index,” which is a functional measure of how much force is required to stretch open the esophagus. Previously, the extent of scar tissue in the esophagus could only be evaluated visually during endoscopy, making it challenging to detect the early changes and intervene before the damage becomes more extensive.
“This is a gamechanger in how we care for kids with EoE,” said senior author Joshua Wechsler, MD, MSCI, Medical Director of Eosinophilic Gastrointestinal Diseases Program at Lurie Children’s, CURED Research Scholar at Lurie Children’s, and Assistant Professor of Pediatrics at Northwestern University Feinberg School of Medicine. “Now, if distensibility is low, we can dilate the esophagus during the same procedure, and because we can pinpoint exactly where the scarring is, our intervention is more targeted and takes much less time. We are seeing improvements in symptoms, which is incredibly exciting.”
Research at Ann & Robert H. Lurie Children’s Hospital of Chicago is conducted through Stanley Manne Children’s Research Institute. The Manne Research Institute is focused on improving child health, transforming pediatric medicine and ensuring healthier futures through the relentless pursuit of knowledge. Lurie Children’s is ranked as one of the nation’s top children’s hospitals by U.S. News & World Report. It is the pediatric training ground for Northwestern University Feinberg School of Medicine.
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Study explores the use of telemedicine in child neurology in largest study to date

Researchers from the Epilepsy Neurogenetics Initiative (ENGIN) at Children’s Hospital of Philadelphia (CHOP) found that across nearly 50,000 visits, patients continued to use telemedicine effectively even with the reopening of outpatient clinics a year after the onset of the COVID-19 pandemic. However, prominent barriers for socially vulnerable families and racial and ethnic minorities persist, suggesting more work is required to reach a wider population with telemedicine.
The findings, which represent the largest study of telemedicine in child neurology to date, were published today by the journal Developmental Medicine & Child Neurology.
The COVID-19 pandemic prompted a rapid and unprecedented conversion of outpatient clinical care from in-person visits to remote telehealth visits. While telemedicine had been used to deliver care for specific adult patient populations prior to the pandemic, the effectiveness of telemedicine in child neurology as a novel method of care had not been systematically explored. In a prior study published by Neurology in 2020, CHOP researchers found that patients and clinicians had a high rate of satisfaction with telemedicine and many on both sides were interested in using telemedicine for future visits.
To that end, the study team wanted to determine the long-term impact of telemedicine on child neurology care during the COVID-19 pandemic, factoring in the reopening of outpatient clinics. The observational study was based on a cohort of 34,837 in-person visits and 14,820 telemedicine outpatient visits between October 2019 and April 2021 across a total of 26,399 child neurology patients.
“In 2020, the COVID-19 pandemic necessitated the use of telemedicine visits, but now that telemedicine visits have been established as part of the care we are able to deliver, we had the opportunity to compare them more thoroughly to in-person visits,” said the study’s first author Michael Kaufman, MS, a data scientist with ENGIN at CHOP. “With data on nearly 15,000 telemedicine visits, we were able to identify trends in how telemedicine was being used by individuals of different demographic backgrounds, neurological conditions and other variables.”
The researchers found that telemedicine was a viable option for many patients and was utilized more often than in-person visits for certain patients, such as those with epilepsy and attention-deficit hyperactivity disorder. Other patients, such as those with certain neuromuscular and movement disorders, younger patients, and those needing specific procedures were less likely to receive care by telemedicine.
Additionally, the researchers found that self-reported racial and ethnic minority populations in the study as well as those with the highest social vulnerability — a measure of community resilience to stressors on human health — were less likely to participate in telemedicine visits. Two novel metrics were developed to determine access to telemedicine and track delayed care, which revealed further disparities. Some of the most vulnerable individuals were less likely to activate their online patient portals and were more likely to receive delayed care, compared to less vulnerable individuals.
“Our group has studied telemedicine extensively, and our findings demonstrate how telemedicine has become a standard component of child neurology care for many patients,” said Ingo Helbig, MD, a pediatric neurologist at CHOP, director of the genomic and data science core of CHOP’s Epilepsy Neurogenetics Initiative (ENGIN) and senior author on this study. “Increased use of telemedicine was prompted by a public health emergency, and so we need to make sure, as these new tools for patient care remain prevalent, that we’re continuing to learn about and address disparities in care and optimize access for socially vulnerable families, so that they have the tools necessary should another similar public health crisis occur.”
This study was supported by The Hartwell Foundation through an Individual Biomedical Research Award; the National Institute for Neurological Disorders and Stroke grants K02 NS112600 and K23 NS102521; the Center Without Walls on ion channel function in epilepsy “Channelopathy-associated Research Center” grant U54 NS108874; the Eunice Kennedy Shriver National Institute of Child Health and Human Development through the Intellectual and Developmental Disabilities Research Center (IDDRC) at Children’s Hospital of Philadelphia and the University of Pennsylvania grant U54 HD086984; intramural funds of Children’s Hospital of Philadelphia through the Epilepsy NeuroGenetics Initiative (ENGIN); and the National Center for Advancing Translational Sciences of the National Institutes of Health through the Institute for Translational Medicine and Therapeutics’ (ITMAT) Transdisciplinary Program in Translational Medicine and Therapeutics at the Perelman School of Medicine of the University of Pennsylvania grant UL1TR001878.
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Researchers identify a gene therapy target for polycystic kidney disease

Blocking the inhibition of PKD1 and PKD2 gene expression by deleting a binding site for microRNAs hindered the formation and growth of kidney cysts in autosomal dominant polycystic kidney disease (ADPKD) models, UT Southwestern researchers reported. The findings, published in Nature Communications, suggest a strategy for gene therapy with the potential to arrest or cure ADPKD.
“For more than 25 years, we have known that ADPKD is caused by mutations of PKD1 or PKD2 genes. Yet, no therapeutic strategy exists to go after these root causes,” said Vishal Patel, M.D., Associate Professor of Internal Medicine in the Division of Nephrology at UTSW and corresponding author of the paper.
ADPKD is among the most common human genetic conditions and the most frequent genetic cause of kidney failure, affecting an estimated 12.5 million people worldwide. ADPKD is an inherited disease in which patients typically inherit one mutated copy of PKD1 (or PKD2) and one normal copy. The disease is characterized by the frequent formation of many small fluid-filled sacs called kidney cysts, which are believed to form when the levels of PKD1 or PKD2 fall below a critical threshold. This can occur when the normal copy of the gene does not produce enough of the proteins Polycystin-1/Polycystin-2.
Proteins are produced (or translated) from a gene’s messenger ribonucleic acid (mRNA). At one end of the mRNA strand is a region of code that helps protect it from degradation but can also control how much of the protein is made. The binding of microRNAs to this region of the mRNA code can block translation, leading to production of less protein.
PKD1 contains a binding site for miR-17, a microRNA that is highly expressed and active in models of ADPKD. So, Dr. Patel and his colleagues asked if blocking the binding of miR-17 to PKD1 could prevent kidney cyst formation.
The researchers deleted the miR-17 binding site from PKD1 mRNA in cell cultures and an ADPKD mouse model. Their results indicated that deletion of the binding site increased stability of the mRNA strand, raised Polycystin-1 levels, and decreased kidney cyst growth. Moreover, the group found that blocking miR-17 binding to PKD1 mRNA with an anti-miR-17 drug after cyst formation also decreased cyst growth, indicating that this interaction could be a promising target for polycystic kidney disease (PKD) treatment.
“There are numerous genetic conditions where one copy of the causative gene is mutated, but the other copy is still normal. Our approach to harnessing the remaining normal copy is likely applicable to many other diseases besides PKD,” said Dr. Patel.
UT Southwestern opened a PKD and genetic kidney disease clinic in 2016 that is co-led by Ronak Lakhia, M.D., Assistant Professor of Internal Medicine in the Division of Nephrology at UTSW. Dr. Lakhia is the co-first author on this study with Harini Ramalingam, Ph.D., a postdoctoral researcher in the Patel lab. The UTSW PKD clinic is now the largest such clinic in Texas, said Dr. Lakhia, gaining recognition as a site for innovative clinical trials.
Other researchers who contributed to this study include Patricia Cobo-Stark, Laurence Biggers, Andrea Flaten, and Jesus Alvarez, all of UTSW; and Chun-Mien Chang, Tania Valencia, Darren P. Wallace, and Edmund C. Lee.
This work was supported by grants from the National Institutes of Health (R01DK102572) and the Department of Defense (D01 W81XWH1810673). Dr. Patel has patents involving anti-miR-17 for the treatment of ADPKD and serves as a scientific consultant for Regulus Therapeutics and other companies as disclosed in the paper.
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How to Change Minds? A Study Makes the Case for Talking It Out.

Researchers found that meaty conversations among several people can align beliefs and brain patterns — so long as the group is free of blowhards.Co-workers stuck on a Zoom call, deliberating a new strategy for a crucial project. Roommates at the kitchen table, arguing about how to split utility bills fairly. Neighbors at a city meeting, debating how to pay for street repairs.We’ve all been there — in a group, trying our best to get everyone on the same page. It’s arguably one of the most important and common undertakings in human societies. But reaching agreement can be excruciating.“Much of our lives seem to be in this sort of Rashomon situation — people see things in different ways and have different accounts of what’s happening,” Beau Sievers, a social neuroscientist at Dartmouth College, said.A few years ago, Dr. Sievers devised a study to improve understanding of how exactly a group of people achieves a consensus and how their individual brains changed after such discussions. The results, recently published online but not yet peer-reviewed, showed that a robust conversation that results in consensus synchronizes the talkers’ brains — not only when thinking about the topic that was explicitly discussed, but related situations that were not.The study also revealed at least one factor that makes it harder to reach accord: a group member whose strident opinions drown out everyone else.“Conversation is our greatest tool to align minds,” said Thalia Wheatley, a social neuroscientist at Dartmouth College who advises Dr. Sievers. “We don’t think in a vacuum, but with other people.”Dr. Sievers designed the experiment around watching movies because he wanted to create a realistic situation in which participants could show fast and meaningful changes in their opinions. But he said it was surprisingly difficult to find films with scenes that could be viewed in different ways. “Directors of movies are very good at constraining the kinds of interpretations that you might have,” he said.Reasoning that smash hits typically did not offer much ambiguity, Dr. Sievers focused on films that critics loved but did not bring blockbuster audiences, including “The Master,” “Sexy Beast” and “Birth,” a 2004 drama in which a mysterious young boy shows up at a woman’s engagement party.None of the study’s volunteers had seen any of the films before. While lying in a brain scanner, they watched scenes from the various movies without sound, including one from “Birth” in which the boy collapses in a hallway after a tense conversation with the elegantly dressed woman and her fiancé.Part of a scene from the 2004 film “Birth,” that was used in a study of how brain patterns are affected by group conversations that yield a consensus agreement.After watching the clips, the volunteers answered survey questions about what they thought had happened in each scene. Then, in groups of three to six people, they sat around a table and discussed their interpretations, with the goal of reaching a consensus explanation.All of the participants were students in the same master of business administration program, and many of them knew each other to varying degrees, which made for lively conversations reflecting real-world social dynamics, the researchers said.After their chats, the students went back into the brain scanners and watched the clips again, as well as new scenes with some of the same characters. The additional “Birth” scene, for example, showed the woman tucking the little boy into bed and crying.After groups reached a consensus explanation about the first film clip, volunteers watched more material, including part of this second scene from “Birth.”The study found that the group members’ brain activity — in regions related to vision, sound, attention, language and memory, among others — became more aligned after their conversation. Intriguingly, their brains were synchronized while they watched the scenes they had discussed, as well as the novel ones.Groups of volunteers came up with different interpretations of the same movie clip. Some groups, for example, thought the woman was the boy’s mother and had abandoned him, whereas others thought they were unrelated. Despite having watched the same clips, the brain patterns from one group to another were meaningfully different, but within each group, the activity was far more synchronized.The results have been submitted for publication in a scientific journal and are under review.“This is a bold and innovative study,” said Yuan Chang Leong, a cognitive neuroscientist at University of Chicago who was not involved in the work.The results jibe with previous research showing people who share beliefs tend to share brain responses. For example, a 2017 study presented volunteers with one of two opposite interpretations of “Pretty Mouth and Green My Eyes,” a short story by J.D. Salinger. The participants that had received the same interpretation had more aligned brain activity when listening to the story in the brain scanner.And in 2020, Dr. Leong’s team reported that when watching news footage, brain activity in conservatives looked more like that in other conservatives than that in liberals, and vice versa.The new study “suggests that the degree of similarity in brain responses depends not only on people’s inherent predispositions, but also the common ground created by having a conversation,” Dr. Leong said.The experiment also underscored a dynamic familiar to anyone who has been steamrollered in a work meeting: An individual’s behavior can drastically influence a group decision. Some of the volunteers tried to persuade their groupmates of a cinematic interpretation with bluster by barking orders and talking over their peers. But others — particularly those who were central players in the students’ real-life social networks — acted as mediators, reading the room and trying to find common ground.The groups with blowhards were less neurally aligned than were those with mediators, the study found. Perhaps more surprising, the mediators drove consensus not by pushing their own interpretations, but by encouraging others to take the stage and then adjusting their own beliefs — and brain patterns — to match the group.“Being willing to change your own mind, then, seems key to getting everyone on the same page,” Dr. Wheatley said.Because the volunteers were eagerly trying to collaborate, the researchers said that the study’s results were most relevant to situations, like workplaces or jury rooms, in which people are working toward a common goal.But what about more adversarial scenarios, in which people have a vested interest in a particular position? The study’s results might not hold for a person negotiating a raise or politicians arguing over the integrity of our elections. And for some situations, like creative brainstorming, groupthink may not be an ideal outcome.“The topic of conversation in this study was probably pretty ‘safe,’ in that no personally or societally relevant beliefs were at stake,” said Suzanne Dikker, a cognitive neuroscientist and linguist at New York University, who was not involved in the study.Future studies could zero in on brain activity during consensus-building conversations, she said. This would require a relatively new technique, known as hyperscanning, which can simultaneously measure multiple people’s brains. Dr. Dikker’s work in this arena has shown that personality traits and conversational dynamics like taking turns can affect brain-to-brain synchrony.Dr. Wheatley agreed. The neuroscientist said she has long been frustrated with her field’s focus on the isolated brain.“Our brains evolved to be social: We need frequent interaction and conversation to stay sane,” she said. “And yet, neuroscience still putters along mapping out the single brain as if that will achieve a deep understanding of the human mind. This has to, and will, change.”

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Adult ADHD linked to elevated risk of cardiovascular diseases

Adults with ADHD are at greater risk of developing a range of cardiovascular diseases than those without the condition, according to a large observational study led by researchers at Karolinska Institutet and Örebro University in Sweden. The researchers say the findings, published in the journal World Psychiatry, underscore the need to monitor cardiovascular health in people with ADHD.
Attention deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders, with a global prevalence of around 2.5 percent in adults. It often exists in parallel with other psychiatric and physical conditions, some of which have been linked to an increased risk of cardiovascular disease (CVD). But whether ADHD is independently associated with overall and specific cardiovascular diseases has not received as much attention.
In the current study, the researchers sought to unmask the correlation between ADHD and some 20 different cardiovascular diseases when separated from other known risk factors such as type 2 diabetes, obesity, smoking, sleep problems and mental disorders.
“We found that adults with ADHD were more than twice as likely to develop at least one cardiovascular disease, compared with those without ADHD,” says the study’s first author Lin Li, postdoctoral researcher at the Department of Medical Epidemiology and Biostatistics, Karolinska Institutet. “When we accounted for other well-established risk factors for CVDs, the association weakened but still remained significant, which indicates that ADHD is an independent risk factor for a wide range of cardiovascular diseases.”
The findings build on national registry data of more than five million Swedish adults, including some 37,000 people with ADHD. After an average 11.8 years of follow-up, 38 percent of individuals with ADHD had at least one diagnosis of cardiovascular disease, compared with 24 percent of those without ADHD.
Risks were elevated for all types of cardiovascular diseases and especially high for cardiac arrest, hemorrhagic stroke and peripheral vascular diseases. The association was somewhat stronger in men than in women. Some psychiatric comorbidities, especially eating and substance use disorders, significantly increased the risk of cardiovascular disease in people with ADHD. Treatment with stimulants and other psychiatric drugs, such as antidepressants and anxiety-reducing medication, did not materially affect the association between ADHD and cardiovascular disease.
The researchers note that due to the observational nature of the study, the findings cannot establish a causal relationship.
“Clinicians needs to carefully consider psychiatric comorbidity and lifestyle factors to help reduce the CVD risk in individuals with ADHD, but we also need more research to explore plausible biological mechanisms, such as shared genetic components for ADHD and cardiovascular disease,” says the study’s last author Henrik Larsson, professor at the School of Medical Sciences, Örebro University, and affiliated researcher at Karolinska Institutet.
The researchers note the study has some limitations, including a lack of data on some lifestyle related factors, such as diet and physical activity, that could impact the association.
This project has received funding from the European Union’s Horizon 2020 research and innovation programme, the Swedish Research Council, the Swedish Brain Foundation, the Swedish Council for Health, Working Life and Welfare and the Swedish Society for Medical Research.
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Moral values explain differences in COVID-19 vaccination rates across US counties

Even though COVID-19 vaccines are safe, effective and widely available in the United States, many Americans are still hesitant to get vaccinated. Indeed, there are stark disparities in COVID-19 vaccination rates across the United States: In some counties, almost all residents are vaccinated while, in other counties, only a minority of residents are vaccinated. A new study from USC researchers sheds light on the beliefs that underlie these consequential disparities in vaccination rates.
The study, published Wednesday in American Psychologist, found that, in line with what we already know about vaccination behavior, structural barriers such as access to health care, historic undervaccination and political barriers explained why residents of some counties were less likely to be vaccinated against COVID-19. Beyond that, however, the researchers showed that we need to consider Americans’ moral values to understand the stark disparities in COVID-19 vaccination rates.
“If you look at a map of the proportion of vaccinations across U.S. counties, you find very stark differences across counties, across regions and across states,” said Nils Karl Reimer, study co-author and postdoctoral researcher at the USC Dornsife College of Letters, Arts and Sciences. “Our goal is to interrogate why these differences in political ideology coincide with differences in vaccination rates. We know already that, especially in the United States, conservatives and liberals endorse different values.
“The goal of our research was to understand how regional differences can help us explain differences in vaccination rates beyond the structural barriers, and indeed that’s what we found. Moral values help explain these differences, above and beyond the well-known variables of political ideology and structural barriers.”
Fairness, loyalty and purity most impactful values in determining COVID vaccination acceptance
The study rests on moral foundations theory, which argues there are five basic moral foundations: care, fairness, loyalty, authority and purity. Relying on data collected from the crowd-sourced website yourmorals.org — an online platform which collects an array of psychological data — the researchers estimated county-level moral values and county-level conservatism. This data was integrated with county-level vaccination rates from the Centers for Disease Control and Prevention, the U.S. COVID-19 Vaccine Coverage Index and presidential election data to control for variables not included in the study.

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Landscape and climate factors can predict prevalence of Lyme disease bacteria

Predicting Lyme disease hotspots can help public health officials guide resources and proactive messaging to the public. But the ecology of the disease is complex, involving various host animals, black-legged ticks that serve as a disease vector, the disease-causing agent itself, the bacteria Borrelia burgdorferi, and the environment in which they all live.
The study, published in the Journal of Applied Ecology, untangles the relationship between two of these players in Lyme disease ecology: bacteria and the environment. Led by Tam Tran, who earned her doctoral degree in Penn’s Department of Biology in the School of Arts & Sciences, and with mentors Dustin Brisson, a professor in the department, Shane Jensen of the Wharton School, along with colleagues from the New York State Department of Health, the research investigates how variables such as landscape disturbance and climate affect the distribution and abundance of B. burgdorferi. The result is a powerful analytical model that can predict with accuracy the prevalence and distribution of the Lyme disease bacteria on the landscape, potentially a useful public health tool to help mitigate disease transmission.
“We know Lyme disease is a growing threat to public health, yet we haven’t found great ways of addressing it. The number of cases keeps growing,” says Tran, now a medical student at Virginia Commonwealth University. “What’s exciting here is that, by knowing how the environment affects both the tick system and the bacteria, we can predict where and when there will be higher amounts of the pathogen in the landscape.”
In the current study, Tran, Brisson, Jensen, and colleagues focused primarily on what factors influenced B. burgdorferi, the prevalence of which they measured by determining what fraction of blacklegged ticks they sampled were infected with the bacteria. Older attempts to draw connections between Lyme disease and environmental variables have resulted in mixed, unclear, or sometimes even contradictory results, Tran says, in part because the contributions of the “environment” writ large can be so multifaceted.
To build their models, the research team took data collected from nearly 19,000 black-legged ticks between 2009 and 2018 across hundreds of sites within New York state. They assessed how numbers of infected and uninfected ticks at hundreds of locations over more than a decade aligned with local environmental features falling in four broad categories:
1) landscape factors such as elevation, fire history, and distance to infrastructure like roads;
2) vertebrate host population sizes, including people, bears, birds, and deer;

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Repeated infections associated with increased risk of some neurodegenerative diseases

Infections treated with specialty hospital care in early- and mid-life are associated with an increased subsequent risk of Alzheimer’s (AD) and Parkinson’s diseases (PD), but not amyotrophic lateral sclerosis (ALS), according to a new study publishing September 15th in the open-access journal PLOS Medicine by Jiangwei Sun of Karolinska Institute, Sweden, and colleagues.
Experimental studies in animals have suggested that infection plays a role in the development of some neurodegenerative diseases, but supporting evidence in humans is limited. In the new study, researchers used data on people diagnosed with AD, PD or ALS from 1970-2016 in Sweden, as well as five matched controls per case, all identified from the Swedish National Patient Register. The analysis included 291,941 AD cases, 103,919 PD cases and 10,161 ALS cases.
A hospital-treated infection 5 or more years before diagnosis was associated with a 16% higher risk of AD (95%CI: 1.15-1.18, P < 0.001) and a 4% higher risk of PD (95%CI: 1.02-1.06, P < 0.001), with similar risks seen for bacterial, viral and other infections and for different sites of infection. The highest risk of disease was seen in people with multiple hospital-treated infections before the age of 40, with more than double the risk of AD (OR=2.62, 95%CI: 2.52-2.72, P < 0.001) and more than 40% increase in the risk of PD (OR=1.41, 95%CI: 1.29-1.53, 3 44 P < 0.001). No association was observed for ALS, regardless of age at diagnosis. "These findings suggest that infectious events may be a trigger or amplifier of a pre-existing disease process, leading to clinical onset of neurodegenerative disease at a relatively early age," the authors say, while also pointing out that "due to the observational nature of the study, these results do not formally prove a causal link." Sun adds, "Hospital-treated infections, especially in early- and mid-life, were associated with an increased risk of Alzheimer's disease (AD) and Parkinson's disease (PD), primarily among AD and PD cases diagnosed before 60 years." Story Source: Materials provided by PLOS. Note: Content may be edited for style and length.

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Study predicts whether rapid tests will be able to detect future SARS-CoV-2 variants

The availability of rapid antigen tests has significantly advanced efforts to contain the spread of COVID-19, but every new variant of concern raises questions about whether diagnostic tests will still be effective. A new study published in Cell attempts to address these questions by evaluating how rapid tests will perform when challenged with future SARS-CoV-2 variants.
The research team, led by Emory University and funded by the National Institute of Health’s (NIH) Rapid Acceleration of Diagnostics (RADx) Tech program, developed a novel method for evaluating how mutations to SARS-CoV-2 can affect recognition by antibodies used in rapid antigen tests. Because most rapid antigen tests detect the SARS-CoV-2 nucleocapsid protein (N protein), the team directly measured how mutations to the N protein impacted diagnostic antibodies’ ability to recognize their target.
“Based on our findings, none of the major past and present SARS-CoV-2 variants of concern contain mutations that would affect the capability of current rapid antigen tests to detect antibodies,” says first study author Filipp Frank, Ph.D., an assistant professor in the department of biochemistry at Emory University. “Further, these data allow us to look one step ahead and predict test performance against almost any variant that may arise.”
The study used a method called deep mutational scanning to evaluate all possible mutations in the N protein in a single, high-throughput experiment. Researchers then measured the impact of the mutations on their interaction with antibodies used in 11 commercially available rapid antigen tests and identified mutations that may allow for antibody escape.
“Accurate and efficient identification of infected individuals remains a critically important strategy for COVID-19 mitigation, and our study provides information about future SARS-CoV-2 mutations that may interfere with detection,” says senior study author Eric Ortlund, Ph.D., a professor in the department of biochemistry at Emory University. “The results outlined here can allow us to quickly adapt to the virus as new variants continue to emerge, representing an immediate clinical and public health impact.”
Findings show that it’s relatively rare for variants to have mutations to the N protein that allow them to evade diagnostic tests, but there are a small proportion of sequences that could impact detection. Researchers, public health officials, and test manufacturers can use these data to determine if a diagnostic test needs to be evaluated for its ability to detect these mutations or to inform future test design.
“Considering the endless cycle of new variants, the data from this study will be useful for years to come,” says Bruce J. Tromberg, Ph.D., director of the National Institute of Biomedical Imaging and Bioengineering (NIBIB) and lead for the RADx® Tech program at NIH.
While many variants of concern contain multiple mutations to the N protein, the study authors note that their method does not evaluate how multiple mutations could affect diagnostic antibody recognition, representing a limitation of the study.
The project was supported by NIBIB under award numbers 75N92019P00328, U54EB015408, and U54EB027690 as part of the RADx initiative, launched to speed innovation in the development, commercialization and implementation of technologies for COVID-19 testing.
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