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Epigenetics Links Severe Inflammatory Syndrome in Children to COVID Infection

Multisystem Inflammatory Syndrome in Children (MIS-C) is related with the epigenetic deregulation of a set of immune-controlling genes. A new study in…

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Scientists from the Josep Carreras Leukemia Research Institute and the Bellvitge Biomedical Research Institute (IDIBELL), say they have identified an epigenetic signature associated to the development of the Multisystem Inflammatory Syndrome in Children (MIS-C) after a SARS-CoV-2 virus infection. The signature has been named EPIMISC, in line with previous studies on the epigenetics of COVID-19 from the same team, which published this recent study, “Epigenetic profiling linked to multisystem inflammatory syndrome in children (MIS-C): A multicenter, retrospective study,” in eClinicalMedicine.

One of the puzzles of infection with the virus has been the remarkable resilience of children to exhibit severe COVID-19. However, a small percentage of the pediatric population affected by the virus experienced a serious health condition called MIS-C, also known as pediatric inflammatory multisystem syndrome (PIMS), that require admission to intensive care unit in around 60% of cases.

In MIS-C, different parts of the body can become inflamed, including the heart, lungs, kidneys, brain, skin, eyes, or gastrointestinal organs. The factors associated with the appearance of MIS-C beyond the presence of the virus are unknown.

“Most children and adolescents infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain asymptomatic or develop a mild coronavirus disease 2019 (COVID-19) that usually does not require medical intervention,” write the investigators.

“However, a small proportion of pediatric patients develop a severe clinical condition, multisystem inflammatory syndrome in children (MIS-C). The involvement of epigenetics in the control of the immune response and viral activity prompted us to carry out an epigenomic study to uncover target loci regulated by DNA methylation that could be altered upon the appearance of MIS-C.

Manel Esteller, MD, PhD, and Aurora Pujol, MD, PhD, served as the coordinators of the research about epigenetic alterations associated with Multisystem Inflammatory Syndrome in Children (MIS-C), a rare disorder that could appear in pediatric COVID-19. [Josep Carreras Leukemia Research Institute]
“Peripheral blood samples were recruited from 43 confirmed MIS-C patients. 69 non-COVID-19 pediatric samples and 15 COVID-19 pediatric samples without MIS-C were used as controls. The cases in the two groups were mixed and divided into discovery (MIS-C = 29 and non-MIS-C = 56) and validation (MIS-C = 14 and non-MIS-C = 28) cohorts, and balanced for age, gender, and ethnic background. We interrogated 850,000 CpG sites of the human genome for DNA methylation variants.

“The DNA methylation content of 33 CpG loci was linked with the presence of MIS-C. Of these sites, 18 (54.5%) were located in described genes. The top candidate gene was the immune T-cell mediator ZEB2; and others highly ranked candidates included the regulator of natural killer cell functional competence SH2D1B; VWA8, which contains a domain of the Von Willebrand factor A involved in the pediatric hemostasis disease; and human leukocyte antigen complex member HLA-DRB1; in addition to pro-inflammatory genes such as CUL2 and AIM2.

“The identified loci were used to construct a DNA methylation profile (EPIMISC) that was associated with MIS-C in both cohorts. The EPIMISC signature was also overrepresented in Kawasaki disease patients, a childhood pathology with a possible viral trigger, that shares many of the clinical features of MIS-C.

“We have characterized DNA methylation loci that are associated with MIS-C diagnosis. The identified genes are likely contributors to the characteristic exaggerated host inflammatory response observed in these patients. The described epigenetic signature could also provide new targets for more specific therapies for the disorder.”

“The COVID-19 disease in adults is characterized by difficulty breathing, while the studied rare syndrome associated with the same virus in children affects many more organs and can have severe consequences,” said Manel Esteller, MD, PhD, director of the Josep Carreras Leukemia Research Institute (IJC), ICREA Research Professor, and professor of genetics at the University of Barcelona. “As the bases for the disorder are unknown, we decided to compare the epigenome of healthy children, children with COVID-19 without MIS-C, and children with COVID-19 who experienced MIS-C.

“We found that MIS-C is characterized by a specific deregulation of epigenetic cellular programming that leads to a landscape of hyperinflammation that can damage tissues.”

The results of the study showed that specific genes were affected in patients, such as those associated with the activation of T lymphocytes, natural killer cells, the recognition of antigens and coagulation. This pattern of epigenetic deregulation was also observed in Kawasaki Syndrome, another inflammatory disease that peaked in 2009 and possibly linked to infection with the influenza virus A H1N1.

Interestingly, two of the 33 DNA methylation events that define the EPIMISC signature are also characteristic of adults without comorbidities who develop severe COVID-19 disease, as previously defined in the EPICOVID signature found by the same team last year.

This fact confirms that both processes, MIS-C in children and severe acute respiratory distress syndrome in adults, are inflammatory post-infectious complications and could be treated in a different way than the initial phase of the viral infection. On this regard, researchers hypothesize that pharmacological inhibition of the CUL2 gene, a mediator of inflammation, could be useful for MIS-C patients since it is known to protect against hyperinflammatory responses.

“It is interesting to see that two disorders that exhibit similar clinical manifestations, MIS-C and Kawasaki, also share a common epigenetic signature, which is different to the epigenetic signature caused by other viruses including HIV,” noted Aurora Pujol, MD, PhD, IDIBELL.

In the same line, Esteller concludes that “it seems that in both syndromes, MIS-C and Kawasaki, there is an exaggerated reaction of the children’s immune system against a viral attack. Knowing the mechanisms triggering both diseases will give us better tools to diagnose and treat them.”

The post Epigenetics Links Severe Inflammatory Syndrome in Children to COVID Infection appeared first on GEN - Genetic Engineering and Biotechnology News.

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Las Vegas Strip Gets a Brand New Technology

It’s not just Caesars and MGM innovating on the Strip. A number of other companies are trying big idea.

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It's not just Caesars and MGM innovating on the Strip. A number of other companies are trying big idea.

Las Vegas has quietly become a hotbed for innovation. Some of that has been driven by the major casino operators -- Caesars Entertainment (CZR) - Get Caesars Entertainment Inc. Report, MGM Resorts International (MGM) - Get MGM Resorts International Report, Resorts World Las Vegas, and Wynn Resorts (WYNN) - Get Wynn Resorts Limited Report -- trying to outdo each other to win over customers.

Some innovations are ostentatious and hard to miss, like the MSG (MSGE) - Get Madison Square Garden Entertainment Corp. Class A Report Sphere being built at the Venetian. That first-of-its-kind concert venue looks as if it dropped to Earth from a technologically advanced civilization, and it has raised the bar for performance venues.

Many innovations, however, aren't as obvious. Caesars, for example, uses an artificial intelligence text-based concierge that's surprisingly effective. "Ivy," as it goes by, can answer questions, help with mundane tasks like getting clean towels delivered, or advance your issue to a human where needed.

Innovations big and small are happening up, down, and under the Las Vegas Strip. Elon Musk's Boring Co. has been building a network of tunnels under the city that will eventually use driverless Tesla  (TSLA) - Get Tesla Inc. Report electric vehicles to ferry people all over the city. 

That's a revolutionary idea -- but now a rival has emerged.  

Image source: Daniel Kline/TheStreet

Musk Goes Low, Lyft Goes High?

Musk's Boring Co. has a bold plan for more than 50 stations connecting the Las Vegas Strip to the airport, the Convention Center, Allegiant Stadium, and Fremont Street using driverless Teslas. 

Currently, only a small portion of that network has been built -- a section connecting the two halves of the Las Vegas Convention Center (and one connecting Resorts World Las Vegas to that same location.

For Musk and Boring Co., it's all about taking traffic off the city's busy streets and bringing it underground.

"During typical peak hours, driving from the Las Vegas Convention Center to Mandalay Bay, for example, can take up to 30 minutes. The same trip on Vegas Loop will take approximately 3 minutes," the company says on its website.

If Musk's plan is fully built, it'll effectively give Las Vegas a modern subway, helping alleviate road congestion. It will not, however, stop tourists from using ride-share and taxi cabs.

Now, ride-share company Lyft  (LYFT) - Get Lyft Inc. Report has brought a solution to Sin City that may ultimately help it solve another problem: a shortage of taxi and ride-share drivers. 

Lyft Brings Driverless Cars (Sort of) to Las Vegas

Labor in Las Vegas has been in short supply since the pandemic hit. Some people left the city and others found work outside the service-industry jobs that fuel the Las Vegas economy. At times, that has made the wait for a cab, or a ride-share from Uber (UBER) - Get Uber Technologies Inc. Report and Lyft, longer than usual.

Lyft plans to fix that by partnering with Motional to bring Motional's "Ioniq-5-based robotaxi, an autonomous vehicle designed for fully driverless ride-hail operation, to the Lyft network in Las Vegas," the ride-share company shared in a news release.

The Ioniq 5 is Hyundai's  (HYMTF)  prominent EV. Motional is the Boston joint venture between Hyundai and automotive-technology specialist Aptiv.  (APTV) - Get Aptiv PLC Report

"Launching Motional’s all-electric Ioniq 5 on Lyft’s network in Las Vegas represents tremendous progress in our vision to make an electric, autonomous, and shared future a reality for people everywhere," said  Lyft CEO Logan Green.

It's Self-Driving Lyfts, But...

There is, however, a pretty big catch.

"Each vehicle arrives with not one but two backup drivers standing by to take control of the car should anything go wrong" Casino.org's Corey Levitan reported.

Lyft has promised a truly driverless system at some point in 2023, but current laws and the state of driverless technology make the backups necessary.

Motional and Lyft have quietly been testing driverless vehicles in Las Vegas since 2018. In the news release, Lyft explained how the system works.

"This means riders are able to easily control their ride without assistance from a driver. The enhanced experience includes unlocking the doors through the Lyft app and starting the ride or contacting customer support from the new in-car Lyft AV app, an intuitive in-ride display tailored to autonomous ride-sharing," the company said.

Lyft and Boring Co. are not working together. But if Musk's plan takes vehicles off Las Vegas's streets, the new program makes the experience better for any that remain. 

Ride sharing and taxis will continue to cost significantly more than using Boring Co's subway-like system, so it's easy to see how the two options will work well together.   .

 

  

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Elon Musk’s Las Vegas Strip Plan Has Some Competition

It’s not just Caesars and MGM innovating on the Strip. Elon Musk has been tunneling under Las Vegas to solve a big problem, and now he has a rival.

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on

It's not just Caesars and MGM innovating on the Strip. Elon Musk has been tunneling under Las Vegas to solve a big problem, and now he has a rival.

Las Vegas has quietly become a hotbed for innovation. Some of that has been driven by the major casino operators -- Caesars Entertainment (CZR) - Get Caesars Entertainment Inc. Report, MGM Resorts International (MGM) - Get MGM Resorts International Report, Resorts World Las Vegas, and Wynn Resorts (WYNN) - Get Wynn Resorts Limited Report -- trying to outdo each other to win over customers.

Some innovations are ostentatious and hard to miss, like the MSG (MSGE) - Get Madison Square Garden Entertainment Corp. Class A Report Sphere being built at the Venetian. That first-of-its-kind concert venue looks as if it dropped to Earth from a technologically advanced civilization, and it has raised the bar for performance venues.

Many innovations, however, aren't as obvious. Caesars, for example, uses an artificial intelligence text-based concierge that's surprisingly effective. "Ivy," as it goes by, can answer questions, help with mundane tasks like getting clean towels delivered, or advance your issue to a human where needed.

Innovations big and small are happening up, down, and under the Las Vegas Strip. Elon Musk's Boring Co. has been building a network of tunnels under the city that will eventually use driverless Tesla  (TSLA) - Get Tesla Inc. Report electric vehicles to ferry people all over the city. 

That's a revolutionary idea -- but now a rival has emerged.  

Image source: Daniel Kline/TheStreet

Musk Goes Low, Lyft Goes High?

Musk's Boring Co. has a bold plan for more than 50 stations connecting the Las Vegas Strip to the airport, the Convention Center, Allegiant Stadium, and Fremont Street using driverless Teslas. 

Currently, only a small portion of that network has been built -- a section connecting the two halves of the Las Vegas Convention Center (and one connecting Resorts World Las Vegas to that same location.

For Musk and Boring Co., it's all about taking traffic off the city's busy streets and bringing it underground.

"During typical peak hours, driving from the Las Vegas Convention Center to Mandalay Bay, for example, can take up to 30 minutes. The same trip on Vegas Loop will take approximately 3 minutes," the company says on its website.

If Musk's plan is fully built, it'll effectively give Las Vegas a modern subway, helping alleviate road congestion. It will not, however, stop tourists from using ride-share and taxi cabs.

Now, ride-share company Lyft  (LYFT) - Get Lyft Inc. Report has brought a solution to Sin City that may ultimately help it solve another problem: a shortage of taxi and ride-share drivers. 

Lyft Brings Driverless Cars (Sort of) to Las Vegas

Labor in Las Vegas has been in short supply since the pandemic hit. Some people left the city and others found work outside the service-industry jobs that fuel the Las Vegas economy. At times, that has made the wait for a cab, or a ride-share from Uber (UBER) - Get Uber Technologies Inc. Report and Lyft, longer than usual.

Lyft plans to fix that by partnering with Motional to bring Motional's "Ioniq-5-based robotaxi, an autonomous vehicle designed for fully driverless ride-hail operation, to the Lyft network in Las Vegas," the ride-share company shared in a news release.

The Ioniq 5 is Hyundai's  (HYMTF)  prominent EV. Motional is the Boston joint venture between Hyundai and automotive-technology specialist Aptiv.  (APTV) - Get Aptiv PLC Report

"Launching Motional’s all-electric Ioniq 5 on Lyft’s network in Las Vegas represents tremendous progress in our vision to make an electric, autonomous, and shared future a reality for people everywhere," said  Lyft CEO Logan Green.

An Important Caveat

There is, however, a pretty big catch.

"Each vehicle arrives with not one but two backup drivers standing by to take control of the car should anything go wrong" Casino.org's Corey Levitan reported.

Lyft has promised a truly driverless system at some point in 2023, but current laws and the state of driverless technology make the backups necessary.

Motional and Lyft have quietly been testing driverless vehicles in Las Vegas since 2018. In the news release, Lyft explained how the system works.

"This means riders are able to easily control their ride without assistance from a driver. The enhanced experience includes unlocking the doors through the Lyft app and starting the ride or contacting customer support from the new in-car Lyft AV app, an intuitive in-ride display tailored to autonomous ride-sharing," the company said.

Lyft and Boring Co. are not working together. But if Musk's plan takes vehicles off Las Vegas's streets, the new program makes the experience better for any that remain. 

Ride sharing and taxis will continue to cost significantly more than using Boring Co's subway-like system, so it's easy to see how the two options will work well together.   .

 

  

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AEMD: Positive Results in a Range of Conditions, Including COVID-19 & Monkey Pox

By M. Marin
NASDAQ:AEMD
READ THE FULL AEMD RESEARCH REPORT
Expanding the Potential Indications for Hemopurifier Treatment
Aethlon Medical’s (NASDAQ: AEMD)…

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By M. Marin

NASDAQ:AEMD

READ THE FULL AEMD RESEARCH REPORT

Expanding the Potential Indications for Hemopurifier Treatment

Aethlon Medical's (NASDAQ: AEMD) clinical trials are moving forward and expanding, as AEMD continues to demonstrate the effectiveness of its lead product, the Aethlon Hemopurifier®, in a broad range of viruses and conditions in single patient emergency use cases and in in vitro analysis, including COVID-19 and various variants and Monkey Pox, among others. The Aethlon Hemopurifier® is being studied in a severe COVID-19 clinical trial under the company's open IDE (Investigational Device Exemption) for life-threatening viral infections.

The safety and feasibility of the Hemopurifier is being evaluated in an Early Feasibility Study (EFS) that will enroll up to 40 COVID-19 ICU patients. The first patient was enrolled in this study in June 2022 and has completed the Hemopurifier treatment. AEMD has nine fully activated hospitals that are actively screening patients for the trial.

In addition to this study, the Hemopurifier has demonstrated positive results in two severely ill patients under individual emergency use and in in vitro analysis. The Hemopurifier has produced positive results in binding seven variants of the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) virus in vitro, as discussed in an article1  that AEMD's CEO Dr. Charles J. Fisher Jr. and the company's Chief Medical Officer Dr. Steven LaRosa contributed to.

The company is also conducting a study of the impact of the ...

Full story available on Benzinga.com

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