MDedge Neurology

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

A version of this article first appeared on Medscape.com

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

A version of this article first appeared on Medscape.com

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

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.

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.

There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.

Here, in my little three-person office, the only thing my staff can’t do is see patients.

Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.

So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.

At this time, I’ve not only gotten used to it, but really don’t mind it.

We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.

Nobody worries about what to throw together for dinner if they get home late.

In an era where other businesses want to reverse the work-from-home trend, I don’t see an issue with its continuing for some jobs. It saves money on rent, and money and time on transportation.

Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.

Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.

My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.

When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.

I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.

Here, in my little three-person office, the only thing my staff can’t do is see patients.

Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.

So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.

At this time, I’ve not only gotten used to it, but really don’t mind it.

We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.

Nobody worries about what to throw together for dinner if they get home late.

In an era where other businesses want to reverse the work-from-home trend, I don’t see an issue with its continuing for some jobs. It saves money on rent, and money and time on transportation.

Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.

Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.

My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.

When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.

I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

There was a recent post on Sermo about medical office staff cross-training. It talked about the importance of the scheduler being able to cover for the medical assistant (to an extent), a billing person being able to room patients, and so on.

Here, in my little three-person office, the only thing my staff can’t do is see patients.

Actually, more than 2 years out since the pandemic changed everyone’s lives, we’ve settled into a very different cross-training routine. I’m the only one at my office. My medical assistant works from home, far north of me, and so does my scheduler, who is across town.

So, at the office, I handle it all. I check people in, copy insurance cards, collect copays, see patients, and make follow-ups.

At this time, I’ve not only gotten used to it, but really don’t mind it.

We don’t worry about freeway traffic. My staff starts at the exact time each day, and so I don’t worry about one of them being an hour late, trapped behind a rush-hour pile-up on the 101. Staying at home with a sick kid isn’t an issue either, anymore. If my secretary has to make her young daughter lunch, or run her over to a birthday party, I don’t even notice it. If there are any problems, she knows how to reach me. Same with my medical assistant.

Nobody worries about what to throw together for dinner if they get home late.

In an era where other businesses want to reverse the work-from-home trend, I don’t see an issue with its continuing for some jobs. It saves money on rent, and money and time on transportation.

Gas prices, at least for driving to and from work for them, don’t have to be factored into the wage equations. I’d guess it’s about 1,000 gallons of gas a year saved. On a national scale that’s nothing, but to my staff right now that’s $3,000-$4,000 more in their pockets at the end of the year. Not to mention it’s two more cars off the road.

Granted, this doesn’t change what I’m doing. Seeing patients in person is a key part of being a doctor. Some things can be handled equally well over the phone or Zoom, but many can’t. It’s what I signed up for, and I really don’t mind it. Seeing patients is still what I enjoy.

My staff is a lot happier with this arrangement, and I don’t mind it either. I always, by nature, kept a reasonably paced schedule. Trying to shoehorn patients in has never been my way, so I have time to run a credit card or scan insurance information.

When one of my staff goes out of town, the other covers her calls and relays messages to me. Yes, it’s extra work, but no more so than if they were here in person. Probably less.

I’m sure many physicians wouldn’t agree with my office model, but it suits me fine. Cross-training and all.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

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

A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

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

A U.S. neuroscientist claims that some of the studies of the experimental agent, simufilam (Cassava Sciences), a drug that targets amyloid beta (Abeta) in Alzheimer’s disease (AD), are flawed, and, as a result, has taken his concerns to the National Institutes of Health.

Matthew Schrag, MD, PhD, department of neurology, Vanderbilt University Medical Center, Nashville, Tenn., uncovered what he calls inconsistencies in major studies examining the drug.

In a whistleblower report to the NIH about the drug, Dr. Schrag claims that several prominent investigators altered images and reused them over years to support the hypothesis that buildup of amyloid in the brain causes AD. The NIH has funded research into Abeta as a potential cause of AD to the tune of millions of dollars for years.

“This hypothesis has been the central dominant thinking of the field,” Dr. Schrag told this news organization. “A lot of the therapies that have been developed and tested clinically over the last decade focused on the amyloid hypothesis in one formulation or another. So, it’s an important component of the way we think about Alzheimer’s disease,” he added.

In an in-depth article published in Science and written by investigative reporter Charles Piller, Dr. Schrag said he became involved after a colleague suggested he work with an attorney investigating simufilam. The lawyer paid Dr. Schrag $18,000 to investigate the research behind the agent. Cassava Sciences denies any misconduct, according to the article.

Dr. Schrag ran many AD studies through sophisticated imaging software. The effort revealed multiple Western blot images – which scientists use to detect the presence and amount of proteins in a sample – that appeared to be altered.
 

High stakes

Dr. Schrag found “apparently altered or duplicated images in dozens of journal articles,” the Science article states.

“A lot is at stake in terms of getting this right and it’s also important to acknowledge the limitations of what we can do. We were working with what’s published, what’s publicly available, and I think that it raises quite a lot of red flags, but we’ve also not reviewed the original material because it’s simply not available to us,” Dr. Schrag said in an interview.

However, he added that despite these limitations he believes “there’s enough here that it’s important for regulatory bodies to take a closer look at it to make sure that the data is right.”

Science reports that it launched its own independent review, asking several neuroscience experts to also review the research. They agreed with Dr. Schrag’s overall conclusions that something was amiss.

Many of the studies questioned in the whistleblower report involve Sylvain Lesné, PhD, who runs The Lesné Laboratory at the University of Minnesota, Minneapolis, and is an associate professor of neuroscience. His colleague Karen Ashe, MD, PhD, a professor of neurology at the same institution, was also mentioned in the whistleblower report. She was coauthor of a 2006 report in Nature that identified an Abeta subtype as a potential culprit behind AD.

This news organization reached out to Dr. Lesné and Dr. Ashe for comment, but has not received a response.

However, an email from a University of Minnesota spokesperson said the institution is “aware that questions have arisen regarding certain images used in peer-reviewed research publications authored by University faculty Dr. Ashe and Dr. Lesné. The University will follow its processes to review the questions any claims have raised. At this time, we have no further information to provide.”
 

A matter of trust

Dr. Schrag noted the “important trust relationship between patients, physicians and scientists. When we’re exploring diseases that we don’t have good treatments for.” He added that when patients agree to participate in trials and accept the associated risks, “we owe them a very high degree of integrity regarding the foundational data.”

Dr. Schrag also pointed out that there are limited resources to study these diseases. “There is some potential for that to be misdirected. It’s important for us to pay attention to data integrity issues, to make sure that we’re investing in the right places.”

The term “fraud” does not appear in Dr. Schrag’s whistleblower report, nor does he claim misconduct in the report. However, his work has spurred some independent, ongoing investigation into the claims by several journals that published the works in question, including Nature and Science Signaling.

Dr. Schrag said that if his findings are validated through an investigation he would like to see the scientific record corrected.

“Ultimately, I’d like to see a new set of hypotheses given a chance to look at this disease from a new perspective,” he added.

Dr. Schrag noted that the work described in the Science article was performed outside of his employment with Vanderbilt University Medical Center and that his opinions do not necessarily represent the views of Vanderbilt University or Vanderbilt University Medical Center. 

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

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
 

Brain tissue autopsy

“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”

In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.

As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
 

Neurologic symptoms’ molecular basis

Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.

These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.

“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”

Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.

Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
 

‘Brain fog’ explained?

The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.

“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”

The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.

This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.

A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

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

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

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

Few people like to pay taxes, and physicians are no exception.

For the Medscape Physicians and Taxes Report 2022, physicians shared information about their tax debt as well as how they feel about the U.S. tax code, audits, and the prospects for the future.

Even though it may not always seem that way to physicians, their family tax bills – around $75,406 on average – are in line with the other top 10% of U.S. taxpayers, according to an examination of IRS data by the Tax Foundation. However, when it comes to local taxes, the Tax Foundation found that physicians pay more than average. (Forty-three states collect tax on individual incomes.)

The average physician’s family pays a 35% marginal tax rate, compared with the top marginal tax rate in the United States of 37%. (The marginal tax rate is the highest amount of tax charged on each additional dollar after the IRS bracket rates are applied to your income.)

According to Alexis Gallati, founder of Cerebral Tax Advisors, a Knoxville, Tenn.–based firm that caters to medical professionals, doctors also should pay attention to their effective tax rate, or the percentage of income they pay in taxes. It takes into account differing tax rates on ordinary income, capital gains, and other income sources, she says. “It gives a better 30,000-foot view of your tax situation.”

Some high-income families are required to pay the Alternative Minimum Tax (AMT), though in 2019 that applied to only one-tenth of U.S. households. The AMT is designed to make sure that high earners with many options for exemptions and deductions still contribute a minimum amount of tax. Only 13% of physicians surveyed said they paid the AMT, though 29% were unsure.
 

Filing taxes as painful as paying them

According to a 2021 Gallup poll, 50% of Americans think they pay too much tax. (About 44% think their tax bill is about right, and a kindhearted 4% think they pay too little.) Doctors are outliers on this one, with 75% saying they pay too much in taxes.

When asked what they would do to fix the tax system, the physicians in the Medscape survey had a wide array of proposed solutions, from “drop the corporate tax rate to nearly nothing to stimulate the economy” to “everyone should pay equitably. There are too many loopholes for the very wealthy.”

Some of the complaints were less about tax rates than the process of filing. One respondent said: “I would love for this system to not be our personal responsibility. Why should it be my duty to pay someone every year to do my taxes?”

About 48% of physicians prepare their own taxes (about the same percentage as the rest of the population), with most of those filing electronically, primarily because it saves time and the software is easy to use. Intuit TurboTax was the most popular online software, with 22% of respondents saying they currently used this product.

Of those who did pay someone to prepare their taxes, the complexity of their taxes cost them; the average respondent paid about three times the average rate for the service. In the long run, the cost might have been recouped.

Navjeet Chahal, managing partner and CEO of Chahal and Associates, a San Francisco–area firm specializing in working with physicians, points out that tax advisors don’t just fill out the forms; they proactively advise physicians about how they can limit their taxes. And indeed, most respondents feel that they got their money’s worth, with 70% saying their tax preparers charged a fair fee.

Though the physicians surveyed tended to think they pay too much tax, and several mentioned particular gripes with the system, the complexity of the tax code didn’t seem to be a big issue. While 82% of Americans polled in 2021 by Pew Research said they were bothered “a lot” or “some” by the complexity of the tax system, 68% of physicians agreed or slightly agreed that the U.S. tax system “makes sense.”
 

Gimme a break

Physicians are the beneficiaries of several types of tax breaks. Contributing to a pretax 401(k) account was the most common exemption, with 60% of physicians surveyed using this plan. Other tax breaks cited by respondents were: contributing to charity (54%), home mortgage interest (46%), and writing off business expenses (39%).

About one in five physicians has experienced an audit, but that risk has declined significantly in recent years, thanks to tighter IRS budgets. Overall, only about 1 in 167 U.S. taxpayers were audited in 2020, according to the IRS. Even for taxpayers reporting $5 million or more in income, the audit rate is only about 0.25%, the Government Accountability Office says.

The odds of a physician being summoned to a meeting with an auditor probably won’t increase for a few years, Mr. Gallati said. But the good news for doctors is bad news for lower-income Americans. “The IRS is woefully understaffed and underfunded, with the result that the agency is going for lower-hanging fruit and auditing more people in lower income brackets,” she said in an interview.

While one respondent described his experience with the IRS as “the audit from hell,” others thought it not so bad, with 72% saying the auditors treated them fairly. One respondent described the audit as “boring, short, and successful for me. The IRS owed me money.”

When it comes to taxes, physician respondents, on the whole, did not seem to be optimistic about the future. About 61% expect an increase in their tax rate because of Biden administration policies. One respondent veered into hyperbole with the comment: “I believe taxes will increase for physicians until they have no more money!”

Mr. Chahal doesn’t see it that way. He pointed out that recent attempts to raise taxes completely failed. “I personally don’t see that happening unless there’s a significant shift in the House and the Senate.”

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

The long-struggling field of cardiac xenotransplantation has had a very good year.

In January, the University of Maryland made history by keeping a 57-year-old man deemed too sick for a human heart transplant alive for 2 months with a genetically engineered pig heart. On July 12, New York University surgeons reported that heart function was “completely normal with excellent contractility” in two brain-dead patients with pig hearts beating in their chests for 72 hours.

NYU Langone Health

The NYU team approached the project with a decedent model in mind and, after discussions with their IRB equivalent, settled on a 72-hour window because that’s the time they typically keep people ventilated when trying to place their organs, explained Robert A. Montgomery, MD, DPhil, director of the NYU Langone Transplant Institute.

“There’s no real ethical argument for that,” he said in an interview. The consideration is what the family is willing to do when trying to balance doing “something very altruistic and good versus having closure.”

Some families have religious beliefs that burial or interment has to occur very rapidly, whereas others, including one of the family donors, were willing to have the research go on much longer, Dr. Montgomery said. Indeed, the next protocol is being written to consider maintaining the bodies for 2-4 weeks.

“People do vary and you have to kind of accommodate that variation,” he said. “For some people, this isn’t going to be what they’re going to want and that’s why you have to go through the consent process.”
 

Informed authorization

Arthur L. Caplan, PhD, director of medical ethics at the NYU Langone Medical Center, said the Uniform Anatomical Gift Act recognizes an individual’s right to be an organ donor for transplant and research, but it “mentions nothing about maintaining you in a dead state artificially for research purposes.”

“It’s a major shift in what people are thinking about doing when they die or their relatives die,” he said.

Because organ donation is controlled at the state, not federal, level, the possibility of donating organs for xenotransplantation, like medical aid in dying, will vary between states, observed Dr. Caplan. The best way to ensure that patients whose organs are found to be unsuitable for transplantation have the option is to change state laws.

He noted that cases are already springing up where people are requesting postmortem sperm or egg donations without direct consents from the person who died. “So we have this new area opening up of handling the use of the dead body and we need to bring the law into sync with the possibilities that are out there.”

In terms of informed authorization (informed consent is reserved for the living), Dr. Caplan said there should be written evidence the person wanted to be a donor and, while not required by law, all survivors should give their permission and understand what’s going to be done in terms of the experiment, such as the use of animal parts, when the body will be returned, and the possibility of zoonotic viral infection.

“They have to fully accept that the person is dead and we’re just maintaining them artificially,” he said. “There’s no maintaining anyone who’s alive. That’s a source of a lot of confusion.”

Special committees also need to be appointed with voices from people in organ procurement, law, theology, and patient groups to monitor practice to ensure people who have given permission understood the process, that families have their questions answered independent of the research team, and that clear limits are set on how long experiments will last.

As to what those limits should be: “I think in terms of a week or 2,” Dr. Caplan said. “Obviously we could maintain bodies longer and people have. But I think, culturally in our society, going much past that starts to perhaps stress emotionally, psychologically, family and friends about getting closure.”

“I’m not as comfortable when people say things like, ‘How about 2 months?’ ” he said. “That’s a long time to sort of accept the fact that somebody has died but you can’t complete all the things that go along with the death.”

Dr. Caplan is also uncomfortable with the use of one-off emergency authorizations, as used for Maryland resident David Bennett Sr., who was rejected for standard heart transplantation and required mechanical circulatory support to stay alive.

“It’s too premature, I believe, even to try and rescue someone,” he said. “We need to learn more from the deceased models.”
 

A better model

Dr. Montgomery noted that primates are very imperfect models for predicting what’s going to happen in humans, and that in order to do xenotransplantation in living humans, there are only two pathways – the one-off emergency authorization or a clinical phase 1 trial.

The decedent model, he said, “will make human trials safer because it’s an intermediate step. You don’t have a living human’s life on the line when you’re trying to do iterative changes and improve the procedure.”

Joe Carrotta for NYU Langone Health

The team, for example, omitted a perfusion pump that was used in the Maryland case and would likely have made its way into phase 1 trials based on baboon data that suggested it was important to have the heart on the pump for hours before it was transplanted, he said. “We didn’t do any of that. We just did it like we would do a regular heart transplant and it started right up, immediately, and started to work.”

The researchers did not release details on the immunosuppression regimen, but noted that, unlike Maryland, they also did not use the experimental anti-CD40 antibody to tamp down the recipients’ immune system.

Although Mr. Bennett’s autopsy did not show any conventional sign of graft rejection, the transplanted pig heart was infected with porcine cytomegalovirus (PCMV) and Mr. Bennett showed traces of DNA from PCMV in his circulation.
 

Nailing down safety

Dr. Montgomery said he wouldn’t rule out xenotransplantation in a living human, but that the safety issues need to be nailed down. “I think that the tests used on the pig that was the donor for the Bennett case were not sensitive enough for latent virus, and that’s how it slipped through. So there was a bit of going back to the drawing board, really looking at each of the tests, and being sure we had the sensitivity to pick up a latent virus.”

He noted that United Therapeutics, which funded the research and provided the engineered pigs through its subsidiary Revivicor, has created and validated a more sensitive polymerase chain reaction test that covers some 35 different pathogens, microbes, and parasites. NYU has also developed its own platform to repeat the testing and for monitoring after the transplant. “The ones that we’re currently using would have picked up the virus.”

Stuart Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., said “the biggest thing from my perspective is those two amazing families that were willing let this happen. ... If 20 years from now, this is what we’re doing, it’s related to these families being this generous at a really tough time in their lives.”

Dr. Russell said he awaits publication of the data on what the pathology of the heart looks like, but that the experiments “help to give us a lot of reassurance that we don’t need to worry about hyperacute rejection,” which by definition is going to happen in the first 24-48 hours.

That said, longer-term data is essential to potential safety issues. Notably, among the 10 genetic modifications made to the pigs, four were porcine gene knockouts, including a growth hormone receptor knockout to prevent abnormal organ growth inside the recipient’s chest. As a result, the organs seem to be small for the age of the pig and just don’t grow that well, admitted Dr. Montgomery, who said they are currently analyzing this with echocardiography.

Dr. Russell said this may create a sizing issue, but also “if you have a heart that’s more stressed in the pig, from the point of being a donor, maybe it’s not as good a heart as if it was growing normally. But that kind of stuff, I think, is going to take more than two cases and longer-term data to sort out.”

Sharon Hunt, MD, professor emerita, Stanford (Calif.) University Medical Center, and past president of the International Society for Heart Lung Transplantation, said it’s not the technical aspects, but the biology of xenotransplantation that’s really daunting.

“It’s not the physical act of doing it, like they needed a bigger heart or a smaller heart. Those are technical problems but they’ll manage them,” she said. “The big problem is biological – and the bottom line is we don’t really know. We may have overcome hyperacute rejection, which is great, but the rest remains to be seen.”

Dr. Hunt, who worked with heart transplantation pioneer Norman Shumway, MD, and spent decades caring for patients after transplantation, said most families will consent to 24 or 48 hours or even a week of experimentation on a brain-dead loved one, but what the transplant community wants to know is whether this is workable for many months.

“So the fact that the xenotransplant works for 72 hours, yeah, that’s groovy. But, you know, the answer is kind of ‘so what,’ ” she said. “I’d like to see this go for months, like they were trying to do in the human in Maryland.”

For phase 1 trials, even longer-term survival with or without rejection or with rejection that’s treatable is needed, Dr. Hunt suggested.

“We haven’t seen that yet. The Maryland people were very valiant but they lost the cause,” she said. “There’s just so much more to do before we have a viable model to start anything like a phase 1 trial. I’d love it if that happens in my lifetime, but I’m not sure it’s going to.”

Dr. Russell and Dr. Hunt reported no relevant financial relationships. Dr. Caplan reported serving as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and is a contributing author and adviser for Medscape.

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

The long-struggling field of cardiac xenotransplantation has had a very good year.

In January, the University of Maryland made history by keeping a 57-year-old man deemed too sick for a human heart transplant alive for 2 months with a genetically engineered pig heart. On July 12, New York University surgeons reported that heart function was “completely normal with excellent contractility” in two brain-dead patients with pig hearts beating in their chests for 72 hours.

NYU Langone Health

The NYU team approached the project with a decedent model in mind and, after discussions with their IRB equivalent, settled on a 72-hour window because that’s the time they typically keep people ventilated when trying to place their organs, explained Robert A. Montgomery, MD, DPhil, director of the NYU Langone Transplant Institute.

“There’s no real ethical argument for that,” he said in an interview. The consideration is what the family is willing to do when trying to balance doing “something very altruistic and good versus having closure.”

Some families have religious beliefs that burial or interment has to occur very rapidly, whereas others, including one of the family donors, were willing to have the research go on much longer, Dr. Montgomery said. Indeed, the next protocol is being written to consider maintaining the bodies for 2-4 weeks.

“People do vary and you have to kind of accommodate that variation,” he said. “For some people, this isn’t going to be what they’re going to want and that’s why you have to go through the consent process.”
 

Informed authorization

Arthur L. Caplan, PhD, director of medical ethics at the NYU Langone Medical Center, said the Uniform Anatomical Gift Act recognizes an individual’s right to be an organ donor for transplant and research, but it “mentions nothing about maintaining you in a dead state artificially for research purposes.”

“It’s a major shift in what people are thinking about doing when they die or their relatives die,” he said.

Because organ donation is controlled at the state, not federal, level, the possibility of donating organs for xenotransplantation, like medical aid in dying, will vary between states, observed Dr. Caplan. The best way to ensure that patients whose organs are found to be unsuitable for transplantation have the option is to change state laws.

He noted that cases are already springing up where people are requesting postmortem sperm or egg donations without direct consents from the person who died. “So we have this new area opening up of handling the use of the dead body and we need to bring the law into sync with the possibilities that are out there.”

In terms of informed authorization (informed consent is reserved for the living), Dr. Caplan said there should be written evidence the person wanted to be a donor and, while not required by law, all survivors should give their permission and understand what’s going to be done in terms of the experiment, such as the use of animal parts, when the body will be returned, and the possibility of zoonotic viral infection.

“They have to fully accept that the person is dead and we’re just maintaining them artificially,” he said. “There’s no maintaining anyone who’s alive. That’s a source of a lot of confusion.”

Special committees also need to be appointed with voices from people in organ procurement, law, theology, and patient groups to monitor practice to ensure people who have given permission understood the process, that families have their questions answered independent of the research team, and that clear limits are set on how long experiments will last.

As to what those limits should be: “I think in terms of a week or 2,” Dr. Caplan said. “Obviously we could maintain bodies longer and people have. But I think, culturally in our society, going much past that starts to perhaps stress emotionally, psychologically, family and friends about getting closure.”

“I’m not as comfortable when people say things like, ‘How about 2 months?’ ” he said. “That’s a long time to sort of accept the fact that somebody has died but you can’t complete all the things that go along with the death.”

Dr. Caplan is also uncomfortable with the use of one-off emergency authorizations, as used for Maryland resident David Bennett Sr., who was rejected for standard heart transplantation and required mechanical circulatory support to stay alive.

“It’s too premature, I believe, even to try and rescue someone,” he said. “We need to learn more from the deceased models.”
 

A better model

Dr. Montgomery noted that primates are very imperfect models for predicting what’s going to happen in humans, and that in order to do xenotransplantation in living humans, there are only two pathways – the one-off emergency authorization or a clinical phase 1 trial.

The decedent model, he said, “will make human trials safer because it’s an intermediate step. You don’t have a living human’s life on the line when you’re trying to do iterative changes and improve the procedure.”

Joe Carrotta for NYU Langone Health

The team, for example, omitted a perfusion pump that was used in the Maryland case and would likely have made its way into phase 1 trials based on baboon data that suggested it was important to have the heart on the pump for hours before it was transplanted, he said. “We didn’t do any of that. We just did it like we would do a regular heart transplant and it started right up, immediately, and started to work.”

The researchers did not release details on the immunosuppression regimen, but noted that, unlike Maryland, they also did not use the experimental anti-CD40 antibody to tamp down the recipients’ immune system.

Although Mr. Bennett’s autopsy did not show any conventional sign of graft rejection, the transplanted pig heart was infected with porcine cytomegalovirus (PCMV) and Mr. Bennett showed traces of DNA from PCMV in his circulation.
 

Nailing down safety

Dr. Montgomery said he wouldn’t rule out xenotransplantation in a living human, but that the safety issues need to be nailed down. “I think that the tests used on the pig that was the donor for the Bennett case were not sensitive enough for latent virus, and that’s how it slipped through. So there was a bit of going back to the drawing board, really looking at each of the tests, and being sure we had the sensitivity to pick up a latent virus.”

He noted that United Therapeutics, which funded the research and provided the engineered pigs through its subsidiary Revivicor, has created and validated a more sensitive polymerase chain reaction test that covers some 35 different pathogens, microbes, and parasites. NYU has also developed its own platform to repeat the testing and for monitoring after the transplant. “The ones that we’re currently using would have picked up the virus.”

Stuart Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., said “the biggest thing from my perspective is those two amazing families that were willing let this happen. ... If 20 years from now, this is what we’re doing, it’s related to these families being this generous at a really tough time in their lives.”

Dr. Russell said he awaits publication of the data on what the pathology of the heart looks like, but that the experiments “help to give us a lot of reassurance that we don’t need to worry about hyperacute rejection,” which by definition is going to happen in the first 24-48 hours.

That said, longer-term data is essential to potential safety issues. Notably, among the 10 genetic modifications made to the pigs, four were porcine gene knockouts, including a growth hormone receptor knockout to prevent abnormal organ growth inside the recipient’s chest. As a result, the organs seem to be small for the age of the pig and just don’t grow that well, admitted Dr. Montgomery, who said they are currently analyzing this with echocardiography.

Dr. Russell said this may create a sizing issue, but also “if you have a heart that’s more stressed in the pig, from the point of being a donor, maybe it’s not as good a heart as if it was growing normally. But that kind of stuff, I think, is going to take more than two cases and longer-term data to sort out.”

Sharon Hunt, MD, professor emerita, Stanford (Calif.) University Medical Center, and past president of the International Society for Heart Lung Transplantation, said it’s not the technical aspects, but the biology of xenotransplantation that’s really daunting.

“It’s not the physical act of doing it, like they needed a bigger heart or a smaller heart. Those are technical problems but they’ll manage them,” she said. “The big problem is biological – and the bottom line is we don’t really know. We may have overcome hyperacute rejection, which is great, but the rest remains to be seen.”

Dr. Hunt, who worked with heart transplantation pioneer Norman Shumway, MD, and spent decades caring for patients after transplantation, said most families will consent to 24 or 48 hours or even a week of experimentation on a brain-dead loved one, but what the transplant community wants to know is whether this is workable for many months.

“So the fact that the xenotransplant works for 72 hours, yeah, that’s groovy. But, you know, the answer is kind of ‘so what,’ ” she said. “I’d like to see this go for months, like they were trying to do in the human in Maryland.”

For phase 1 trials, even longer-term survival with or without rejection or with rejection that’s treatable is needed, Dr. Hunt suggested.

“We haven’t seen that yet. The Maryland people were very valiant but they lost the cause,” she said. “There’s just so much more to do before we have a viable model to start anything like a phase 1 trial. I’d love it if that happens in my lifetime, but I’m not sure it’s going to.”

Dr. Russell and Dr. Hunt reported no relevant financial relationships. Dr. Caplan reported serving as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and is a contributing author and adviser for Medscape.

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

The long-struggling field of cardiac xenotransplantation has had a very good year.

In January, the University of Maryland made history by keeping a 57-year-old man deemed too sick for a human heart transplant alive for 2 months with a genetically engineered pig heart. On July 12, New York University surgeons reported that heart function was “completely normal with excellent contractility” in two brain-dead patients with pig hearts beating in their chests for 72 hours.

NYU Langone Health

The NYU team approached the project with a decedent model in mind and, after discussions with their IRB equivalent, settled on a 72-hour window because that’s the time they typically keep people ventilated when trying to place their organs, explained Robert A. Montgomery, MD, DPhil, director of the NYU Langone Transplant Institute.

“There’s no real ethical argument for that,” he said in an interview. The consideration is what the family is willing to do when trying to balance doing “something very altruistic and good versus having closure.”

Some families have religious beliefs that burial or interment has to occur very rapidly, whereas others, including one of the family donors, were willing to have the research go on much longer, Dr. Montgomery said. Indeed, the next protocol is being written to consider maintaining the bodies for 2-4 weeks.

“People do vary and you have to kind of accommodate that variation,” he said. “For some people, this isn’t going to be what they’re going to want and that’s why you have to go through the consent process.”
 

Informed authorization

Arthur L. Caplan, PhD, director of medical ethics at the NYU Langone Medical Center, said the Uniform Anatomical Gift Act recognizes an individual’s right to be an organ donor for transplant and research, but it “mentions nothing about maintaining you in a dead state artificially for research purposes.”

“It’s a major shift in what people are thinking about doing when they die or their relatives die,” he said.

Because organ donation is controlled at the state, not federal, level, the possibility of donating organs for xenotransplantation, like medical aid in dying, will vary between states, observed Dr. Caplan. The best way to ensure that patients whose organs are found to be unsuitable for transplantation have the option is to change state laws.

He noted that cases are already springing up where people are requesting postmortem sperm or egg donations without direct consents from the person who died. “So we have this new area opening up of handling the use of the dead body and we need to bring the law into sync with the possibilities that are out there.”

In terms of informed authorization (informed consent is reserved for the living), Dr. Caplan said there should be written evidence the person wanted to be a donor and, while not required by law, all survivors should give their permission and understand what’s going to be done in terms of the experiment, such as the use of animal parts, when the body will be returned, and the possibility of zoonotic viral infection.

“They have to fully accept that the person is dead and we’re just maintaining them artificially,” he said. “There’s no maintaining anyone who’s alive. That’s a source of a lot of confusion.”

Special committees also need to be appointed with voices from people in organ procurement, law, theology, and patient groups to monitor practice to ensure people who have given permission understood the process, that families have their questions answered independent of the research team, and that clear limits are set on how long experiments will last.

As to what those limits should be: “I think in terms of a week or 2,” Dr. Caplan said. “Obviously we could maintain bodies longer and people have. But I think, culturally in our society, going much past that starts to perhaps stress emotionally, psychologically, family and friends about getting closure.”

“I’m not as comfortable when people say things like, ‘How about 2 months?’ ” he said. “That’s a long time to sort of accept the fact that somebody has died but you can’t complete all the things that go along with the death.”

Dr. Caplan is also uncomfortable with the use of one-off emergency authorizations, as used for Maryland resident David Bennett Sr., who was rejected for standard heart transplantation and required mechanical circulatory support to stay alive.

“It’s too premature, I believe, even to try and rescue someone,” he said. “We need to learn more from the deceased models.”
 

A better model

Dr. Montgomery noted that primates are very imperfect models for predicting what’s going to happen in humans, and that in order to do xenotransplantation in living humans, there are only two pathways – the one-off emergency authorization or a clinical phase 1 trial.

The decedent model, he said, “will make human trials safer because it’s an intermediate step. You don’t have a living human’s life on the line when you’re trying to do iterative changes and improve the procedure.”

Joe Carrotta for NYU Langone Health

The team, for example, omitted a perfusion pump that was used in the Maryland case and would likely have made its way into phase 1 trials based on baboon data that suggested it was important to have the heart on the pump for hours before it was transplanted, he said. “We didn’t do any of that. We just did it like we would do a regular heart transplant and it started right up, immediately, and started to work.”

The researchers did not release details on the immunosuppression regimen, but noted that, unlike Maryland, they also did not use the experimental anti-CD40 antibody to tamp down the recipients’ immune system.

Although Mr. Bennett’s autopsy did not show any conventional sign of graft rejection, the transplanted pig heart was infected with porcine cytomegalovirus (PCMV) and Mr. Bennett showed traces of DNA from PCMV in his circulation.
 

Nailing down safety

Dr. Montgomery said he wouldn’t rule out xenotransplantation in a living human, but that the safety issues need to be nailed down. “I think that the tests used on the pig that was the donor for the Bennett case were not sensitive enough for latent virus, and that’s how it slipped through. So there was a bit of going back to the drawing board, really looking at each of the tests, and being sure we had the sensitivity to pick up a latent virus.”

He noted that United Therapeutics, which funded the research and provided the engineered pigs through its subsidiary Revivicor, has created and validated a more sensitive polymerase chain reaction test that covers some 35 different pathogens, microbes, and parasites. NYU has also developed its own platform to repeat the testing and for monitoring after the transplant. “The ones that we’re currently using would have picked up the virus.”

Stuart Russell, MD, a professor of medicine who specializes in advanced HF at Duke University, Durham, N.C., said “the biggest thing from my perspective is those two amazing families that were willing let this happen. ... If 20 years from now, this is what we’re doing, it’s related to these families being this generous at a really tough time in their lives.”

Dr. Russell said he awaits publication of the data on what the pathology of the heart looks like, but that the experiments “help to give us a lot of reassurance that we don’t need to worry about hyperacute rejection,” which by definition is going to happen in the first 24-48 hours.

That said, longer-term data is essential to potential safety issues. Notably, among the 10 genetic modifications made to the pigs, four were porcine gene knockouts, including a growth hormone receptor knockout to prevent abnormal organ growth inside the recipient’s chest. As a result, the organs seem to be small for the age of the pig and just don’t grow that well, admitted Dr. Montgomery, who said they are currently analyzing this with echocardiography.

Dr. Russell said this may create a sizing issue, but also “if you have a heart that’s more stressed in the pig, from the point of being a donor, maybe it’s not as good a heart as if it was growing normally. But that kind of stuff, I think, is going to take more than two cases and longer-term data to sort out.”

Sharon Hunt, MD, professor emerita, Stanford (Calif.) University Medical Center, and past president of the International Society for Heart Lung Transplantation, said it’s not the technical aspects, but the biology of xenotransplantation that’s really daunting.

“It’s not the physical act of doing it, like they needed a bigger heart or a smaller heart. Those are technical problems but they’ll manage them,” she said. “The big problem is biological – and the bottom line is we don’t really know. We may have overcome hyperacute rejection, which is great, but the rest remains to be seen.”

Dr. Hunt, who worked with heart transplantation pioneer Norman Shumway, MD, and spent decades caring for patients after transplantation, said most families will consent to 24 or 48 hours or even a week of experimentation on a brain-dead loved one, but what the transplant community wants to know is whether this is workable for many months.

“So the fact that the xenotransplant works for 72 hours, yeah, that’s groovy. But, you know, the answer is kind of ‘so what,’ ” she said. “I’d like to see this go for months, like they were trying to do in the human in Maryland.”

For phase 1 trials, even longer-term survival with or without rejection or with rejection that’s treatable is needed, Dr. Hunt suggested.

“We haven’t seen that yet. The Maryland people were very valiant but they lost the cause,” she said. “There’s just so much more to do before we have a viable model to start anything like a phase 1 trial. I’d love it if that happens in my lifetime, but I’m not sure it’s going to.”

Dr. Russell and Dr. Hunt reported no relevant financial relationships. Dr. Caplan reported serving as a director, officer, partner, employee, advisor, consultant, or trustee for Johnson & Johnson’s Panel for Compassionate Drug Use (unpaid position) and is a contributing author and adviser for Medscape.

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

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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

New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.

“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.

Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.

The most recent data from the Centers for Disease Control and Prevention has found that one in 13 adults in the United States – 7.5% – have symptoms that last at least 3 months after they first came down with the virus. Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.

Unfortunately, there’s no easy way to screen for long COVID.

“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”

It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
 

What to look for

Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”

More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.

“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.

This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.

“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.

Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.

One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:

• Headache.
• Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
• Dizziness when standing.
• Pins-and-needles feelings.
• Changes in smell or taste.
• Depression or anxiety.

You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
 

Risk of having other health conditions

People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:

• Type 2 diabetes.
• Kidney failure.
• Pulmonary embolism, or a blood clot in the lung.
• Myocarditis, an inflamed heart.

While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.

“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.

COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
 

Is it long COVID or something else?

Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.

They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.

“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.

What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.

“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”

Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”

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