Journal of Clinical Outcomes Management

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

A version of this article first appeared on Medscape.com.

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

A version of this article first appeared on Medscape.com.

Dozens of University of Michigan, Ann Arbor, medical students walked out of their white coat ceremony July 24 as a keynote speaker began to talk.

A Twitter video of the walkout has gone viral. By press time, the video had garnered more than 9.5 million views.

The walkout comes days after more than 340 medical students at the school signed a petition opposing the selection of Michigan assistant professor Kristin Collier, MD, for the ceremony because of her anti-abortion views, according to The Michigan Daily.

In response to the incident, a medical school spokeswoman told this news organization that Dr. Collier was chosen to be speaker “based on nominations and voting by members of the UM Medical School Gold Humanism Honor Society, which is comprised of medical students, house officers, and faculty.”

The press statement continued, “The White Coat Ceremony is not a platform for discussion of controversial issues. Its focus will always be on welcoming students into the profession of medicine. Dr. Collier never planned to address a divisive topic as part of her remarks. However, the University of Michigan does not revoke an invitation to a speaker based on their personal beliefs.”

The university further stated that it remains committed to providing reproductive care for patients, including abortion care, which remains legal in Michigan following the recent U.S. Supreme Court ruling overturning abortion rights, according to the statement by Mary Masson, director of Michigan Medicine public relations.

The state has an abortion ban, but a recent court order temporarily blocked enforcement of it, according to the statement.

In her speech, Dr. Collier recognized the divisiveness of the issue. “I want to acknowledge the deep wounds our community has suffered over the past several weeks. We have a great deal of work to do for healing to occur. And I hope for today, for this time, we can focus on what matters the most, coming together with a goal to support our newly accepted students and their families.”

Following applause from the remaining audience, she continued to offer advice for the incoming students about how to thrive in their chosen profession.

Dr. Collier, a graduate of the med school and director of its Health, Spirituality, and Religion program, has 15.2K Twitter followers. She has been known to post anti-abortion sentiments, including those cited in the students’ petition.

“While we support the rights of freedom of speech and religion, an anti-choice speaker as a representative of the University of Michigan undermines the University’s position on abortion and supports the non-universal, theology-rooted platform to restrict abortion access, an essential part of medical care,” the petition reads, in part.

The petition states that the disagreement is not over personal opinions. “We demand that UM stands in solidarity with us and selects a speaker whose values align with institutional policies, students, and the broader medical community. This speaker should inspire the next generation of health care providers to be courageous advocates for patient autonomy and our communities.”

A version of this article first appeared on Medscape.com.

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

A version of this article first appeared on WebMD.com.

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

A version of this article first appeared on WebMD.com.

As scientists work on wearable technology that promises to revolutionize health care, researchers from the University of Texas at Austin and Texas A&M University, College Station, are reporting a big win in the pursuit of one highly popular target: a noninvasive solution for continuous blood pressure monitoring at home.

Not only that, but this development comes in the surprising form of a temporary tattoo. That’s right: Just like the kind that children like to wear.

The thin, sticker-like wearable electronic tattoos can provide continuous, accurate blood pressure monitoring, the researchers report in their new study.

“With this new technology, we are going to have an opportunity to understand how our blood pressure fluctuates during the day. We will be able to quantify how stress is impacting us,” says Roozbeh Jafari, PhD, a professor of biomedical engineering, electrical engineering, and computer science at Texas A&M, College Station, and a coauthor of the study.
 

Revealing the whole picture, not just dots

At-home blood pressure monitors have been around for many years now. They work just like the blood pressure machines doctors use at their office: You place your arm inside a cuff, press a button, feel a squeeze on your arm, and get a reading.

While results from this method are accurate, they are also just a moment in time. Our blood pressure can vary greatly throughout the day – especially among people who have labile hypertension, where blood pressure changes from one extreme to the other. So, looking at point-in-time readings is a bit like focusing on a few dots inside of a pointillism painting – one might miss the bigger picture.

Doctors may also find continuous monitoring useful for getting rid of false readings from “white coat syndrome.” Basically, this means a person’s blood pressure rises due to the anxiety of being in a doctor’s office but is not true hypertension.

Bottom line: The ability to monitor a person’s blood pressure continuously for hours or even days can provide clearer, and more accurate, insights into a person’s health.
 

How do health monitoring tattoos work?

Electronic tattoos for health monitoring are not completely new. John A. Rogers, PhD, of Northwestern University, Chicago, first put forth the idea of monitoring through temporary tattoos 12 years ago. Some concepts, such as UV monitoring tattoos, had already been adopted by scientists and put on the market. But the existing models weren’t suitable for monitoring blood pressure, according to Deji Akinwande, PhD, a professor of electrical and computer engineering at the University of Texas at Austin and another coauthor of the study.

“[UV monitoring tattoos] are very thick,” he says. “They create too much movement when used to measure blood pressure because they slide around.”

So, the Texas-based research team worked to develop an option that was slimmer and more stable.

“The key ingredient within e-tattoos is graphene,” says Dr. Akinwande.

Graphene is carbon that’s similar to what’s inside your graphite pencil. The material is conductive, meaning it can conduct small electrical currents through the skin. For blood pressure monitoring, graphene promotes bioelectrical impedance analysis (BIA), which is like the technology used in smart scales that measure body fat.

With e-tattoos, the thin layers of graphene stick to the skin and do not slide around, getting rid of “artifacts,” or bad data. The graphene e-tattoos can be worn on the skin for about a week – or roughly as long as the temporary tattoos kids love.

Once the graphene captures the raw data, a machine learning algorithm interprets the information and provides results in units used for measuring blood pressure: millimeters of mercury (mmHg), commonly referred to as blood pressure “points.”

How accurate are the results? The tests measured blood pressure within 0.2 ± 5.8 mmHg (systolic), 0.2 ± 4.5 mmHg (diastolic), and 0.1 ± 5.3 mmHg (mean arterial pressure). In other words: If this were a basketball player shooting baskets, the great majority of shots taken would be swishes and occasionally a few would hit the rim. That means good accuracy.
 

When will e-tattoos be available?

The teams of Dr. Jafari and Dr. Akinwande are working on a second generation of their e-tattoo that they expect to be available in the next 5 years.

The upgrade they envision will be smaller and compatible with smartwatches and phones that use Bluetooth technology and near-field communication (NFC) to transfer data and give it power. With these updates, e-tattoos for continuous blood pressure monitoring will be ready for clinical trials and mainstream use soon after.

“Everyone can benefit from knowing their blood pressure recordings,” Dr. Akinwande says. “It is not just for people at risk for hypertension but for others to proactively monitor their health, for stress and other factors.”

A version of this article first appeared on WebMD.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Researchers from France have identified two distinct phenotypes of fulminant COVID-19–related myocarditis in adults, with different clinical presentations, immunologic profiles, and outcomes.

Differentiation between the two bioclinical entities is important to understand for patient management and further pathophysiological studies, they said.

The first phenotype occurs early (within a few days) in acute SARS-CoV-2 infection, with active viral replication (polymerase chain reaction positive) in adults who meet criteria for multisystem inflammatory syndrome (MIS-A+).

Floaria Bicher/iStock/Getty Images Plus

In this early phenotype, there is “limited systemic inflammation without skin and mucosal involvement, but myocardial dysfunction is fulminant and frequently associated with large pericardial effusions. These cases more often require extracorporeal membrane oxygenation [ECMO],” Guy Gorochov, MD, PhD, Sorbonne University, Paris, said in an interview.

The second is a delayed, postinfectious, immune-driven phenotype that occurs in adults who fail to meet the criteria for MIS-A (MIS-A–).

This phenotype occurs weeks after SARS-CoV-2 infection, usually beyond detectable active viral replication (PCR–) in the context of specific immune response and severe systemic inflammation with skin and mucosal involvement. Myocardial dysfunction is more progressive and rarely associated with large pericardial effusions, Dr. Gorochov explained.

The study was published in the Journal of the American College of Cardiology.
 

Evolving understanding

The findings are based on a retrospective analysis of 38 patients without a history of COVID-19 vaccination who were admitted to the intensive care unit from March 2020 to June 2021 for suspected fulminant COVID-19 myocarditis.

Patients were confirmed to have SARS-CoV-2 infection by PCR and/or by serologic testing. As noted in other studies, the patients were predominantly young men (66%; median age, 27.5 years). Twenty-five (66%) patients were MIS-A+ and 13 (34%) were MIS-A–.

In general, the MIS-A– patients were sicker and had worse outcomes.

Specifically, compared with the MIS-A+ patients, MIS-A– patients had a shorter time between the onset of COVID-19 symptoms and the development of myocarditis, a shorter time to ICU admission, and more severe presentations assessed using lower left ventricular ejection fraction and sequential organ failure assessment scores.

MIS-A– patients also had higher lactate levels, were more likely to need venoarterial ECMO (92% vs 16%), had higher ICU mortality (31% vs. 4%), and a had lower probability of survival at 3 months (68% vs. 96%), compared with their MIS-A+ peers.

Immunologic differences

The immunologic profiles of these two distinct clinical phenotypes also differed.

In MIS-A– early-type COVID-19 myocarditis, RNA polymerase III autoantibodies are frequently positive and serum levels of antiviral interferon-alpha and granulocyte-attracting interleukin-8 are elevated.

In contrast, in MIS-A+ delayed-type COVID-19 myocarditis, RNA polymerase III autoantibodies are negative and serum levels of IL-17 and IL-22 are highly elevated.

“We suggest that IL-17 and IL-22 are novel criteria that should help to assess in adults the recently recognized MIS-A,” Dr. Gorochov told this news organization. “It should be tested whether IL-17 and IL-22 are also elevated in children with MIS-C.”

The researchers also observed “extremely” high serum IL-10 levels in both patient groups. This has been previously associated with severe myocardial injury and an increase in the risk for death in severe COVID-19 patients.

The researchers said the phenotypic clustering of patients with fulminant COVID-19–related myocarditis “seems relevant” for their management.

MIS-A– cases, owing to the high risk for evolution toward refractory cardiogenic shock, should be “urgently” referred to a center with venoarterial ECMO and closely monitored to prevent a “too-late” cannulation, especially under cardiopulmonary resuscitation, known to be associated with poor outcomes, they advised.

They noted that the five patients who died in their series had late venoarterial ECMO implantation, while undergoing multiple organ failures or resuscitation.

Conversely, the risk for evolution to refractory cardiogenic shock is lower in MIS-A+ cases. However, identifying MIS-A+ cases is “all the more important given that numerous data support the efficacy of corticosteroids and/or intravenous immunoglobulins in MIS-C,” Dr. Gorochov and colleagues wrote.

The authors of a linked editorial said the French team should be “commended on their work in furthering our understanding of fulminant myocarditis related to COVID-19 infection.”

Ajith Nair, MD, Baylor College of Medicine, and Anita Deswal, MD, MPH, University of Texas M.D. Anderson Cancer Center, both in Houston, noted that fulminant myocarditis is rare and can result from either of two mechanisms: viral tropism or an immune-mediated mechanism.

“It remains to be seen whether using antiviral therapy versus immunomodulatory therapy on the basis of clinical and cytokine profiles will yield benefits,” they wrote.

“Fulminant myocarditis invariably requires hemodynamic support and carries a high mortality risk if it is recognized late. However, the long-term prognosis in patients who survive the critical period is favorable, with recovery of myocardial function,” they added.

“This study highlights the ever-shifting understanding of the pathophysiology and therapeutic approaches to fulminant myocarditis,” Dr. Nair and Dr. Deswal concluded.

This research was supported in part by the Foundation of France, French National Research Agency, Sorbonne University, and Clinical Research Hospital. The researchers have filed a patent application based on these results. Dr. Nair and Dr. Deswal have no relevant disclosures.

A version of this article first appeared on Medscape.com.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

A version of this article first appeared on Medscape.com.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.

Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.

The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.

“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
 

SWIFT-DIRECT

SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.

Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).

With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).

“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.

“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.

There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).

Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
 

DIRECT-SAFE

DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.

Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).

Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.

“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.

“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.

To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.

Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.

Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.

SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.

A version of this article first appeared on Medscape.com.

Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.

Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.

The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.

“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
 

SWIFT-DIRECT

SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.

Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).

With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).

“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.

“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.

There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).

Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
 

DIRECT-SAFE

DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.

Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).

Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.

“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.

“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.

To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.

Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.

Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.

SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.

A version of this article first appeared on Medscape.com.

Two new noninferiority trials address the controversial question of whether thrombolytic therapy can be omitted for acute ischemic stroke in patients undergoing endovascular thrombectomy for large-vessel occlusion.

Both trials show better outcomes when standard bridging thrombolytic therapy is used before thrombectomy, with comparable safety.

The results of SWIFT-DIRECT and DIRECT-SAFE were published online June 22 in The Lancet.

“The case appears closed. Bypass intravenous thrombolysis is highly unlikely to be noninferior to standard care by a clinically acceptable margin for most patients,” writes Pooja Khatri, MD, MSc, department of neurology, University of Cincinnati, in a linked comment.
 

SWIFT-DIRECT

SWIFT-DIRECT enrolled 408 patients (median age 72; 51% women) with acute stroke due to large vessel occlusion admitted to stroke centers in Europe and Canada. Half were randomly allocated to thrombectomy alone and half to intravenous alteplase and thrombectomy.

Successful reperfusion was less common in patients who had thrombectomy alone (91% vs. 96%; risk difference −5.1%; 95% confidence interval, −10.2 to 0.0, P = .047).

With combination therapy, more patients achieved functional independence with a modified Rankin scale score of 0-2 at 90 days (65% vs. 57%; adjusted risk difference −7.3%; 95% CI, −16·6 to 2·1, lower limit of one-sided 95% CI, −15·1%, crossing the noninferiority margin of −12%).

“Despite a very liberal noninferiority margin and strict inclusion and exclusion criteria aimed at studying a population most likely to benefit from thrombectomy alone, point estimates directionally favored intravenous thrombolysis plus thrombectomy,” Urs Fischer, MD, cochair of the Stroke Center, University Hospital Basel, Switzerland, told this news organization.

“Furthermore, we could demonstrate that overall reperfusion rates were extremely high and yet significantly better in patients receiving intravenous thrombolysis plus thrombectomy than in patients treated with thrombectomy alone, a finding which has not been shown before,” Dr. Fischer said.

There was no significant difference in the risk of symptomatic intracranial bleeding (3% with combination therapy and 2% with thrombectomy alone).

Based on the results, in patients suitable for thrombolysis, skipping it before thrombectomy “is not justified,” the study team concludes.
 

DIRECT-SAFE

DIRECT-SAFE enrolled 295 patients (median age 69; 43% women) with stroke and large vessel occlusion from Australia, New Zealand, China, and Vietnam, with half undergoing direct thrombectomy and half bridging therapy first.

Functional independence (modified Rankin Scale 0-2 or return to baseline at 90 days) was more common in the bridging group (61% vs. 55%).

Safety outcomes were similar between groups. Symptomatic intracerebral hemorrhage occurred in 2 (1%) patients in the direct group and 1 (1%) patient in the bridging group. There were 22 (15%) deaths in the direct group and 24 in the bridging group.

“There has been concern across the world regarding cost of treatment, together with fears of increasing bleeding risk or clot migration with intravenous thrombolytic,” lead investigator Peter Mitchell, MBBS, director, NeuroIntervention Service, The Royal Melbourne Hospital, Parkville, Victoria, Australia, told this news organization.

“We showed that patients in the bridging treatment arm had better outcomes across the entire study, especially in Asian region patients” and therefore remains “the gold standard,” Dr. Mitchell said.

To date, six published trials have addressed this question of endovascular therapy alone or with thrombolysis – SKIP, DIRECT-MT, MR CLEAN NO IV, SWIFT-DIRECT, and DIRECT-SAFE.

Dr. Fischer said the SWIFT-DIRECT study group plans to perform an individual participant data meta-analysis known as Improving Reperfusion Strategies in Ischemic Stroke (IRIS) of all six trials to see whether there are subgroups of patients in whom thrombectomy alone is as effective as thrombolysis plus thrombectomy.

Subgroups of interest, he said, include patients with early ischemic signs on imaging, those at increased risk for hemorrhagic complications, and patients with a high clot burden.

SWIFT-DIRECT was funding by Medtronic and University Hospital Bern. DIRECT-SAFE was funded by Australian National Health and Medical Research Council and Stryker USA. A complete list of author disclosures is available with the original articles.

A version of this article first appeared on Medscape.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.

The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.

“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.

Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.

“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”

Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.

For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.

“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.

Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.

Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.

Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.

“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”

It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.

The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.

“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.

There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.

“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.

As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.

“For the first time in months, I was feeling like myself again,” she said.

But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.

“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.

She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.

For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.

“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”

Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.

“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”

A version of this article first appeared on WebMD.com.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.

What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.

“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.

Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”

Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.

This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
 

Lingering inflammation may be the culprit

Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.

“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”

While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.

While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.

“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.

Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.

However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.

“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.

This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

A version of this article first appeared on Medscape.com.

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

A version of this article first appeared on Medscape.com.

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

A version of this article first appeared on Medscape.com.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.

As the number of monkeypox cases keeps growing, a discussion has opened on whether it should be considered a sexually transmitted disease like herpes, gonorrhea, or HIV.

Monkeypox is almost always spread through skin-to-skin contact and, in the West, many of the cases have occurred among men who have sex with men.

But health experts say that doesn’t make it an STD – at least not in “the classic sense.”

“Monkeypox is not a sexually transmitted disease in the classic sense (by which it’s spread in the semen or vaginal fluids), but it is spread by close physical contact with lesions,” infectious diseases expert Robert L. Murphy, MD, of Northwestern Medicine, Chicago, said in a news release.

He said the current monkeypox outbreak was more like a meningitis outbreak among gay men a few years ago.

Rowland Kao, PhD, a professor of veterinary epidemiology and data science at the University of Edinburgh, said that an “STD is one where intimate, sexual contact is critical to the transmission – where sexual acts are central to the transmission,” Newsweek reported.

“Some infections are transmitted by any type of close contact, of which sexual activity is one. Monkeypox is one of those – it’s the close contact that matters, not the sexual activity itself.”

But calling monkeypox an STD could deter measures to limit its spread, another expert told Newsweek.

“My uneasiness about labeling it as an STD is that for most STDs, wearing a condom or avoiding penetration or direct oral-anal/oral-genital contact is a good way of preventing transmission,” said Paul Hunter, MD, a professor of health protection at the University of East Anglia, Norwich, England.

“But for monkeypox, even just naked cuddling is a big risk. So labeling it an STD could actually work against control if people felt they just had to wear a condom.”

Denise Dewald, MD, a pediatric specialist at University Hospitals Cleveland Medical Center, said monkeypox is not an STD – but it could become an entrenched virus.

“Monkeypox will become established in the pediatric and general population and will transmit through daycares and schools,” she tweeted. “It is not an STD. It is like MRSA. This isn’t rocket science.”

One thing is certain: More and more people are getting monkeypox. It’s been endemic in Western and Central Africa for years, and cases in Europe and North America were identified in May.

Globally, more than 14,000 cases have been identified, World Health Organization Director-General Tedros Adhanom Ghebreyesus said on July 20, according to the Center for Infectious Disease Research and Policy. Five people in Africa have died. In the United Kingdom, more than 2,100 cases have been identified.

In the United States, more than 2,500 confirmed monkeypox cases have been detected, with cases reported from every state except Alaska, Maine, Montana, Mississippi, Vermont, and Wyoming, the CDC said on July 21.

A version of this article first appeared on WebMD.com.