Journal of Clinical Outcomes Management

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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

Although recent months have seen the arrival of several promising vaccines to combat COVID-19, many researchers have been concerned about the shortage of Black and Latinx volunteers in their pivotal trials.

Sean Warren/iStockphoto.com

Minority groups have long been underrepresented in clinical research. The pandemic’s inequitable fallout has heightened the need for more inclusive COVID-19 trials. By one estimate, Black Americans are three times more likely to become infected with SARS-Cov-2 and twice as likely to die from it, compared with their White counterparts.

It was therefore welcome news this past November when the Maryland-based biotech company Novavax unveiled their plans to boost participation among specific minority groups during the phase 3 trial of their COVID-19 vaccine candidate NVX-CoV2373. To help them in their efforts, the company tapped Howard University, in Washington, D.C., to be a clinical test site. The goal was to enroll 300 Black and Latinx volunteers through a recruitment registry at the Coronavirus Prevention Network.

“We have seen quite a good number of participants in the registry, and many are African American, who are the ones we are trying to reach in the trial,” explained Siham Mahgoub, MD, medical director of the Center of Infectious Diseases Management and Research and principal investigator for the Novavax trial at Howard University, Washington. “It’s very important for people of color to participate in the trial because we want to make sure these vaccines work in people of color,” Dr. Mahgoub said.

Over the years, Howard University has hosted several important clinical trials and studies, and its participation in the multi-institutional Georgetown–Howard Universities Center for Clinical and Translational Science consortium brings crucial infrastructural value. By bringing this vaccine trial to one of the most esteemed historically Black colleges or universities (HBCUs), researchers hoped to address a sense of hesitancy among possible participants that is prompted in part by the tragic history of medical testing in the Black community.

“The community trusts Howard,” said Dr. Mahgoub. “I think it’s great having Howard and an HBCU host this trial, because these are people who look like them.”

Novavax deliberately sought an HBCU to work with on this trial to help people of color feel more at ease and increase minority participation. Lisa M. Dunkle, MD, vice president and global medical lead for coronavirus vaccine at Novavax, explained that, in addition to Howard being located close to the company’s headquarters, the university seemed like a great fit for the overall mission.

“As part of our goal to achieve a representative trial population that includes communities who are disproportionately impacted by the pandemic, we sought out some of the HBCUs to include in our trial sites. We hoped that this might encourage people of color to enroll and to increase their comfort level with vaccines in general,” Dr. Dunkle said.
 

Building more representative clinical trials

For decades, research on some of the most groundbreaking vaccines and treatments have been based on the results of studies conducted with predominately White participants, despite the fact that a much more demographically varied general population would ultimately receive them. This has led to calls to include people of different races and ethnic backgrounds in trials.

Homogeneity in clinical trials is discouraged, but trials are not heavily regulated in this regard. In 1993, Congress passed the Revitalization Act, which requires that trials that are conducted by the National Institutes of Health include women and members of minority groups among their cohorts. However, the number or proportion of such participants is not specified.

Underrepresentation in clinical trials also reflects a general unwillingness by members of ethnic minorities to volunteer because of the deeply unsettling history of such trials in minority communities. Among some Black persons, it is not uncommon for names like Tuskegee, Henrietta Lacks, and J. Marion Simms to be mentioned when giving reasons for not participating.

“There is certainly some dark history in how minorities have been treated by our health care system, and it’s not surprising that there is some fear and distrust,” said Dr. Dunkle. “By recruiting people of color into clinical trials that are governed with strict standards, we can begin to change perceptions and attitudes.”

Vaccine hesitancy is not only rooted in the past. The current state of medical care also has some potential trial participants worried. Misinformation, inequity in health care access, and low health literacy contribute to the current fears of scientific development.
 

A trial designed to engender trust

Having information about the vaccine come from trusted voices in the community is a key means of overcoming hesitancy. Howard University President Wayne Frederick, MD, reached out to a pastor of a local Black church to have more participants enroll in the trial. One who answered the call to action was Stephanie Williams, an elementary school teacher in Montgomery County, Maryland. When she saw that her pastor was participating in the Novavax trial and when she considered the devastation she had seen from COVID-19, she was on board.

“We had about three sessions where he shared his experiences. He also shared some links to read about it more,” Ms. Williams said. “When I saw that he took it, that gave me a lot of confidence. Since I’m going be going into the classroom, I wanted to be sure that I was well protected.”

Transparency is key to gaining more participation, explained Dr. Maghoub. Webinar-based information sessions have proven particularly important in achieving this.

“We do a lot of explaining in very simple language to make sure everyone understands about the vaccine. The participants have time to ask questions during the webinar, and at any time [during the trial], if a participant feels that it is not right for them, they can stop. They have time to learn about the trial and give consent. People often think they are like guinea pigs in trials, but they are not. They must give consent.”

There are signs that the approach has been successful. Over a period of 4-5 weeks, the Howard site enrolled 150 participants, of whom 30% were Black and 20% were Latinx.

Novavax has been in business for more than 3 decades but hasn’t seen the booming success that their competitors have. The company has noted progress in developing vaccines against Middle East respiratory syndrome and severe acute respiratory syndrome. However, they missed the mark in clinical trials, failing twice in 3 years to develop a respiratory syncytial virus vaccine administered through maternal immunizations.

From being on the verge of closing, Novavax has since made a dramatic turnaround after former President Trump awarded the company $1.6 billion dollars in July 2020 as part of Operation Warp Speed. If trial results are promising, the Novavax vaccine could enter the market in a few months, representing not only a new therapeutic option but perhaps a new model for building inclusivity in clinical trials.

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

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Approximately 40,000 children in the United States have lost a parent to COVID-19, based on data from a combination of death counts and simulation models.

dtiberio/iStock/Getty Images

The scale of mortality from COVID-19 among adults in the United States merits efforts to monitor how many children have lost a parent as a result of the pandemic, wrote Rachel Kidman, PhD, of Stony Brook (N.Y.) University and colleagues.

In a study published in JAMA Pediatrics, the researchers used kinship networks of White and Black individuals in the United States to estimate parental bereavement. They combined deaths from COVID-19 as of February 2021 and combined them with excess deaths, and estimated future bereavement based on a herd immunity scenario.

Overall, the model suggested that each death from COVID-19 results in potential parental bereavement for 0.78 children aged 0-17 years, representing an increase of 17.5%-20.2% in parental bereavement. The model indicated that, as of February 2021, 37,337 children aged 0-17 years had lost a parent to COVID-19, including 11,366 children age 0-9 years and 31,661 children and teens aged 10-17 years. A total of 20,600 of these children were non-Hispanic White and 7,600 were Black. Black children accounted for 20% of the bereaved children, although they account for approximately 14% of children aged 0-17 years in the United States, the researchers noted.

Including the excess death estimate, which refers to the difference between observed and expected deaths for the remainder of the pandemic, raised the total bereaved children to 43,000. A future mortality scenario using a total of 1,500,000 deaths from COVID-19 based on a natural herd immunity strategy increased the total estimate of bereaved children to 116,922.

The study findings were limited by several factors including the lack of data on nonparental primary caregivers, and the use of demographic models rather than survey or administrative data, the researchers noted.

However, the huge number of children who have experienced the death of a parent because of COVID-19 emphasizes the need for reforms to address health, educational, and economic impacts of this mass bereavement on children and teens, they said.

“Parentally bereaved children will also need targeted support to help with grief, particularly during this period of heightened social isolation,” they emphasized.

Establishment of a national child bereavement cohort could identify children early in the bereavement process to help ensure that they are connected to local supportive care and monitored for health and behavior problems, the researchers said. In addition, such a cohort could be used as a basis for a longitudinal study of the impact of mass parental bereavement during a unique period of social isolation and economic uncertainty, they concluded.
 

Study spotlights gaps in mental health care

The study is an important reminder of how COVID-19 has disrupted children’s lives, said Herschel Lessin, MD, of Children’s Medical Group in Poughkeepsie, N.Y., in an interview. Losing a parent because of COVID-19 is one more tragedy on the list of social and emotional disasters the pandemic has wrought on children, he said.

“There has to be some sort of national response to help children through all of this, not just one item at a time,” Dr. Lessin said. However, the management of children’s mental health in the United States has been subpar for decades, he noted, with few clinicians trained to specialize in treating behavioral and mental health issues in children. Consequently, more general pediatricians will continue to be faced with the mental health issues of bereaved children who desperately need support, he said.

Money remains a key barrier, as it keeps qualified clinicians from entering the field of pediatric mental and behavioral health, and even where there are mental health providers, most do not take insurance and have long waiting lists, Dr. Lessin noted.

General pediatricians were seeing more patients with ADHD, anxiety, and depression before the advent of COVID-19, though most are not trained in managing these conditions, said Dr. Lessin. “Approximately 25%-30% of my visits now are mental health related, and the pandemic will make it geometrically worse,” he said.

The current study, with its dramatic estimates of the number of children who have lost a parent because of COVID-19, may bring attention to the fact that more training and money are needed to support mental health programs for children, he said.

Lead author Dr. Kidman had no financial conflicts to disclose. The study was supported by grants to corresponding author Ashton M. Verdery, PhD, from the National Institute on Aging and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. Dr. Lessin had no financial conflicts but serves on the Pediatric News editorial advisory board.

SOURCE: Kidman R et al. JAMA Pediatr. .

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

Patients with rheumatic heart disease (RHD) appear to have comparable outcomes, whether undergoing transcatheter or surgical aortic valve replacement (TAVR/SAVR), and when compared with TAVR in patients with nonrheumatic aortic stenosis, a new Medicare study finds.

An analysis of data from 1,159 Medicare beneficiaries with rheumatic aortic stenosis revealed that, over a median follow-up of 19 months, there was no difference in all-cause mortality with TAVR vs. SAVR (11.2 vs. 7.0 per 100 person-years; adjusted hazard ratio, 1.53; P = .2).

Mortality was also similar after a median follow-up of 17 months between TAVR in patients with rheumatic aortic stenosis and 88,554 additional beneficiaries with nonrheumatic aortic stenosis (15.2 vs. 17.7 deaths per 100 person-years; aHR, 0.87; P = .2).

“We need collaboration between industry and society leaders in developed countries to initiate a randomized, controlled trial to address the feasibility of TAVR in rheumatic heart disease in younger populations who aren’t surgical candidates or if there’s a lack of surgical capabilities in countries, but this is an encouraging first sign,” lead author Amgad Mentias, MD, MSc, Cleveland Clinic Foundation, said in an interview.

Although the prevalence of rheumatic heart disease (RHD) has fallen to less than 5% or so in the United States and Europe, it remains a significant problem in developing and low-income countries, with more than 1 million deaths per year, he noted. RHD patients typically present at younger ages, often with concomitant aortic regurgitation and mitral valve disease, but have less calcification than degenerative calcific aortic stenosis.

Commenting on the results, published in the Journal of the American College of Cardiology, David F. Williams, PhD, said in an interview that “it is only now becoming possible to entertain the use of TAVR in such patients, and this paper demonstrates the feasibility of doing so.

“Although the study is based on geriatric patients of an industrialized country, it opens the door to the massive unmet clinical needs in poorer regions as well as emerging economies,” said Dr. Williams, a professor at the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., and coauthor of an accompanying editorial.

The study included Medicare beneficiaries treated from October 2015 to December 2017 for rheumatic aortic stenosis (TAVR, n = 605; SAVR, n = 55) or nonrheumatic aortic stenosis (n = 88,554).

Among those with rheumatic disease, SAVR patients were younger than TAVR patients (73.4 vs. 79.4 years), had a lower prevalence of most comorbidities, and were less frail (median frailty score, 5.3 vs. 11.3).

SAVR was associated with significantly higher weighted risk for in-hospital acute kidney injury (22.3% vs. 11.9%), blood transfusion (19.8% vs. 7.6%), cardiogenic shock (5.7% vs. 1.5%), new-onset atrial fibrillation (21.1% vs. 2.2%), and had longer hospital stays (median, 8 vs. 3 days), whereas new permanent pacemaker implantations trended higher with TAVR (12.5% vs 7.2%).

The TAVR and SAVR groups had comparable rates of adjusted in-hospital mortality (2.4% vs. 3.5%), 30-day mortality (3.6% vs. 3.2%), 30-day stroke (2.4% vs. 2.8%), and 1-year mortality (13.1% vs. 8.9%).

Among the two TAVR cohorts, patients with rheumatic disease were younger than those with nonrheumatic aortic stenosis (79.4 vs. 81.2 years); had a higher prevalence of heart failure, ischemic stroke, atrial fibrillation, and lung disease; and were more frail (median score, 11.3 vs. 6.9).

Still, there was no difference in weighted risk of in-hospital mortality (2.2% vs. 2.6%), 30-day mortality (3.6% vs. 3.7%), 30-day stroke (2.0% vs. 3.3%), or 1-year mortality (16.0% vs. 17.1%) between TAVR patients with and without rheumatic stenosis.

“We didn’t have specific information on echo[cardiography], so we don’t know how that affected our results, but one of the encouraging points is that after a median follow-up of almost 2 years, none of the patients who had TAVR in the rheumatic valve and who survived required redo aortic valve replacement,” Dr. Mentias said. “It’s still short term but it shows that for the short to mid term, the valve is durable.”

Data were not available on paravalvular regurgitation, an Achilles heel for TAVR, but Dr. Mentias said rates of this complication have come down significantly in the past 2 years with modifications to newer-generation TAVR valves.

Dr. Williams and colleagues say one main limitation of the study also highlights the major shortcoming of contemporary TAVRs when treating patients with RHD: “namely, their inadequate suitability for AR [aortic regurgitation], the predominant rheumatic lesion of the aortic valve” in low- to middle-income countries.

They pointed out that patients needing an aortic valve where RHD is rampant are at least 30 years younger than the 79-year-old TAVR recipients in the study.

In a comment, Dr. Williams said there are several unanswered questions about the full impact TAVR could have in the treatment of young RHD patients in underprivileged regions. “These mainly concern the durability of the valves in individuals who could expect greater longevity than the typical heart valve patient in the USA, and the adaptation of transcatheter techniques to provide cost-effective treatment in regions that lack the usual sophisticated clinical infrastructure.”

Dr. Mentias received support from a National Research Service Award institutional grant to the Abboud Cardiovascular Research Center. Dr. Williams and coauthors are directors of Strait Access Technologies.

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

COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
 

In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.

The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.  

“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.

Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.

The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
 

High rate of neurologic, psychiatric disorders

The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period. 

All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.

The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.

The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.

The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.

Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.

“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.

Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
 

Largest study to date

Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.

There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.

“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.

In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.

Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”

“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”

Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
 

Need for replication

Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.

“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.

“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.

Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.

“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.

Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
 

Beyond a reasonable doubt

Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”

Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added. 

“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.    

“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”

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

COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
 

In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.

The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.  

“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.

Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.

The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
 

High rate of neurologic, psychiatric disorders

The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period. 

All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.

The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.

The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.

The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.

Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.

“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.

Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
 

Largest study to date

Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.

There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.

“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.

In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.

Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”

“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”

Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
 

Need for replication

Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.

“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.

“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.

Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.

“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.

Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
 

Beyond a reasonable doubt

Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”

Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added. 

“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.    

“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”

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

COVID-19 survivors face a sharply elevated risk of developing psychiatric or neurologic disorders in the 6 months after they contract the virus – a danger that mounts with symptom severity, new research shows.
 

In what is purported to be the largest study of its kind to date, results showed that among 236,379 COVID-19 patients, one-third were diagnosed with at least 1 of 14 psychiatric or neurologic disorders within a 6-month span.

The rate of illnesses, which ranged from depression to stroke, rose sharply among those with COVID-19 symptoms acute enough to require hospitalization.  

“If we look at patients who were hospitalized, that rate increased to 39%, and then increased to about just under 1 in 2 patients who needed ICU admission at the time of the COVID-19 diagnosis,” Maxime Taquet, PhD, University of Oxford (England) department of psychiatry, said at a media briefing.

Incidence jumps to almost two-thirds in patients with encephalopathy at the time of COVID-19 diagnosis, he added.

The study, which examined the brain health of 236,379 survivors of COVID-19 via a U.S. database of 81 million electronic health records, was published online April 6 in The Lancet Psychiatry.
 

High rate of neurologic, psychiatric disorders

The research team looked at the first-time diagnosis or recurrence of 14 neurologic and psychiatric outcomes in patients with confirmed SARS-CoV-2 infections. They also compared the brain health of this cohort with a control group of those with influenza or with non–COVID-19 respiratory infections over the same period. 

All study participants were older than 10 years, diagnosed with COVID-19 on or after Jan. 20, 2020, and still alive as of Dec. 13, 2020.

The psychiatric and neurologic conditions examined included intracranial hemorrhage; ischemic stroke; parkinsonism; Guillain-Barré syndrome; nerve, nerve root and plexus disorders; myoneural junction and muscle disease; encephalitis; dementia; psychotic, mood, and anxiety disorders; substance use disorder; and insomnia.

The investigators used hospitalization, intensive care admissions, and encephalopathy as an indication of the severity of COVID-19 symptoms.

The study benchmarked the primary cohort with four populations of patients diagnosed in the same period with nonrespiratory illnesses, including skin infection, urolithiasis, bone fractures, and pulmonary embolisms.

Results showed that substantially more COVID-19 patients were diagnosed with a neurologic or psychiatric disorder compared with those with other respiratory illnesses.

“On average, in terms of the relative numbers, there was a 44% increased risk of having a neurological or psychiatric diagnosis after COVID-19 than after the flu and a 16% increased risk compared to other respiratory tract infections,” Dr. Taquet told reporters.

Health services should be prepared for an increase in psychiatric and neurologic issues in the months to come, he said, adding that further investigations are needed into why, and how, the coronavirus affects brain health.
 

Largest study to date

Although previous research suggests a link between the two, this is the largest study of its kind, examines a wider range of neurologic outcomes, and spans the longest time frame to date, said study coinvestigator Paul Harrison, BM BCh, associate head of the University of Oxford department of psychiatry.

There was a lower incidence of mood and anxiety disorders vs. neurologic disorders in patients with severe COVID-19 symptoms, a finding that Dr. Harrison said may indicate pandemic-related psychological stress is driving these disorders vs. biological factors.

“This paper follows up on an earlier study we did where we found much the same association, and our view is that a lot of the mental health consequences of COVID are … to do with the stress of knowing that one has had COVID and all the implications that go with that, rather than its being a direct effect, for example, of the virus on the brain, or of the immune response to the virus on the brain,” he added.

In contrast, neurologic diagnoses were more likely to be “mediated by some direct consequence of the COVID infection,” he added.

Psychosis and dementia, for instance, were less frequent in the overall COVID-19 population but became much more frequent among those with severe symptoms. The research team said these findings, along with those related to the incidence of ischemic stroke, were “concerning.”

“We found that 1 in 50 patients with COVID-19 go on to have an ischemic stroke in the 6 months after the COVID-19 illness,” Dr. Taquet told reporters. “And that rate increased to 1 in 11 patients if we look at patients with encephalopathy at the time of the COVID-19 diagnosis.”

Rates of brain hemorrhages also rose sharply among those with acute symptoms. Just over 1 in 200 total COVID-19 patients were diagnosed with this neurological condition, but that jumped to 1 in 25 of those who experienced encephalopathy at the time of their COVID-19 diagnosis.
 

Need for replication

Study coauthor Masud Husain, PhD, of University of Oxford’s cognitive neurology department, told reporters that while there is evidence from other neurologic studies that the virus can access the brain, there has been little sign the neurons themselves are affected.

“There isn’t much evidence that the virus itself attacks neurons in the brain, but it can cause inflammation, and it can activate inflammatory cells in the brain,” he said.

“And those effects are probably very important in some of the biological effects on the brain. In addition, of course, we know that the virus can change clotting and the likelihood of thrombosis in the blood, and those effects can also impact upon the brain,” he added.

Dr. Harrison said it would be helpful to replicate the results garnered from the U.S. database in other populations.

“It goes without saying that replication of these results with other electronic health records and in other countries is a priority,” he said, adding that investigations are essential into how and why the virus affects brain health.

Dr. Harrison cited a U.K. Research and Innovation–funded study called COVID CNS that will follow patients with neurologic and/or psychiatric issues during acute COVID-19 in hopes of exploring possible causes.
 

Beyond a reasonable doubt

Commenting on the findings, Sir Simon Wessely, MD, Regius chair of psychiatry, King’s College London, said in a release: “This is a very important paper. It confirms beyond any reasonable doubt that COVID-19 affects both brain and mind in equal measure.”

Some of these effects, including stroke and anxiety disorders, were already known, but others such as dementia and psychosis were less well known, he added. 

“What is very new is the comparisons with all respiratory viruses or influenza, which suggests that these increases are specifically related to COVID-19, and not a general impact of viral infection,” Dr. Wessely said. “In general, the worse the illness, the greater the neurological or psychiatric outcomes, which is perhaps not surprising.    

“The worst outcomes were in those with encephalopathy – inflammation of the brain – again, not surprising. The association with dementia was, however, small and might reflect diagnostic issues, whilst so far there doesn’t seem early evidence of a link with parkinsonism, which was a major factor after the great Spanish Flu pandemic, although the authors caution that it is too early to rule this out.”

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

The COVID-19 pandemic continues to take its toll on the well-being and work satisfaction of health care providers, a new survey of more than 5,000 clinicians at an academic medical center illustrates.

About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.

“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”

“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.

The study was published online April 2 in JAMA Network Open.

“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”

“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
 

When the pandemic hits home

A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.

“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”

To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.

Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”

Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.

The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.

A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
 

COVID-19 career concerns

Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.

The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.

Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.

“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.

Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.

Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.

“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.

“It is critical that we strategically address these important disparities,” she said.

Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.

Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
 

Potential solutions

“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.

Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.

Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.

“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”

The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.

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

The COVID-19 pandemic continues to take its toll on the well-being and work satisfaction of health care providers, a new survey of more than 5,000 clinicians at an academic medical center illustrates.

About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.

“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”

“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.

The study was published online April 2 in JAMA Network Open.

“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”

“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
 

When the pandemic hits home

A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.

“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”

To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.

Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”

Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.

The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.

A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
 

COVID-19 career concerns

Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.

The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.

Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.

“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.

Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.

Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.

“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.

“It is critical that we strategically address these important disparities,” she said.

Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.

Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
 

Potential solutions

“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.

Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.

Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.

“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”

The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.

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

The COVID-19 pandemic continues to take its toll on the well-being and work satisfaction of health care providers, a new survey of more than 5,000 clinicians at an academic medical center illustrates.

About one in five people reported considering leaving the workforce because of the challenges of working during the COVID-19 pandemic. In addition, 30% reported they are considering cutting back work hours.

“There are a substantial number of employees and trainees who are experiencing major stress and work disruptions because of the pandemic,” lead author Rebecca K. Delaney, PhD, said in an interview. “It is particularly alarming that people who have spent 5 or more years in training for their specialty are struggling with their work, so much so that they have even considered leaving the workforce or reducing their hours.”

“Being a caregiver adds another layer of difficulty for faculty, staff, and trainees who are trying to manage work and child care,” added Dr. Delaney, a researcher in the department of population health sciences, University of Utah, Salt Lake City.

The study was published online April 2 in JAMA Network Open.

“This looks like an excellent survey,” Carol A Bernstein, MD, said in an interview when asked to comment. “I do not think it provides particularly new information as these challenges in the workplace, especially for women during COVID, have been well documented in the media and the medical literature to date.”

“That said, to the extent that data helps drive solutions, I would hope that information such as this would be considered as strong further evidence that health care systems must pay close attention to the wellbeing of the workforce,” added Dr. Bernstein, professor and vice chair of faculty development and well-being, departments of psychiatry and behavioral sciences and obstetrics and gynecology and women’s health, Montefiore Medical Center/Albert Einstein College of Medicine, New York.
 

When the pandemic hits home

A total of 42% of the American workforce rapidly transitioned to working from home at the onset of the COVID-19 pandemic. At the same time, many employees had to provide child care and assistance with schoolwork. This placed a burden on many individuals at academic medical centers, and women in particular.

“Women comprise 74.9% of hospital employees, many of whom are essential clinical workers,” the researchers noted. “The extent of the needs and difficulties for these workers during the pandemic remain largely unknown.”

To learn more, Dr. Delaney, senior author Angie Fagerlin, PhD, and their colleagues emailed a Qualtrics survey to 27,700 faculty, staff, and trainees at University of Utah Health. The survey was conducted Aug. 5-20, 2020 as part of a quality improvement initiative. All responses were anonymous.

Survey questions included if, because of the pandemic, people had considered leaving the workforce, considered reducing their hours, or experienced reduced productivity. The researchers also asked about career impacts and potential solutions in terms of “work culture adaptations.”

Respondents with children aged under 18 years also were asked about child care options. Dr. Delaney and colleagues also inquired about race and ethnicity because they hypothesized that employees from underrepresented groups would likely experience the pandemic differently.

The mean age of the 5,951 (21%) faculty, staff, and trainees who completed the survey was 40 years. A majority of respondents were women, reflecting the higher proportion of women within the health system.

A majority (86%) identified as White or European American. About two-thirds of respondents (66%) were staff, 16% were faculty, and 13% were trainees.
 

COVID-19 career concerns

Overall, 1,061 respondents (21%) “moderately or very seriously” considered leaving the workforce and 1,505 (30%) considered reducing hours. Respondents who were younger, married, a member of an underrepresented racial/ethnic group, and worked in a clinical setting were more likely to consider leaving the workforce.

The survey showed 27% felt their productivity increased whereas 39% believed their productivity decreased.

Of the 2,412 survey participants with children aged 18 years or younger, 66% reported that they did not have child care fully available.

“Failure to address and provide for child care has long been one of the many significant deficits in U.S. health care systems,” said Dr. Bernstein, lead author of a March 2021 report evaluating staff emotional support at Montefiore Medical Center during the pandemic in The Joint Commission Journal on Quality and Patient Safety.

Furthermore, 47% were “moderately or very seriously worried” about COVID-19 impacting their career development.

Women trainees were significantly more likely than male counterparts to consider leaving the workforce and reducing their work hours. Women in a faculty or trainee role were also more likely to worry about COVID-19’s impact on their career, compared with men, and compared with women in staff positions.

“It was disheartening to have our data support the gender and racial/ethnic disparity that has been highlighted in the media during the pandemic,” Dr. Delaney said. “Women and in some cases racial/ethnic groups that are underrepresented in medicine were most likely to consider leaving the workforce, reducing hours, and were worried about their career development.

“It is critical that we strategically address these important disparities,” she said.

Women also are disproportionately affected by burnout, particularly during the pandemic, according to an analysis of Medscape’s Physician Burnout and Suicide Report.

Furthermore, the COVID-19 pandemic has shifted the medical specialties now considered highest risk for burnout: critical care physicians ranked first in the report, followed by rheumatologists and infectious disease specialists.
 

Potential solutions

“Given the disproportionate impact COVID-19 has on employees of health systems, institutions must find ways to support their employees, both in terms of workplace cultural adaptations and assistance with familial responsibilities,” the researchers noted.

Telecommuting policies, scheduling flexibility, and expanding employee support programs are potential solutions. Institutional policies also could address the educational and direct care needs of employee children.

Limitations of the study include its generalizability beyond employees of University of Utah Health. Also, respondents included a lower proportion of racial and ethnic groups, compared with national figures, “although this is mostly accounted for by the overall low population of such groups in the state of Utah,” the researchers added.

“Our results suggest that respondents were struggling during the COVID-19 pandemic,” the researchers noted. “As a result, even after investing substantial amounts of time in years of training, many were considering leaving the workforce because of stress and caregiving responsibilities related to the pandemic.”

The Jon M. Huntsman Presidential Endowed Chair supported the work with a financial award to Dr. Fagerlin. Dr. Delaney and Dr. Bernstein disclosed no relevant financial relationships.

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

It is often assumed that cognitive decline is an inevitable part of aging, but a new study of centenarians suggests otherwise.

Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.

“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.

“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.

The study was published online Jan. 15 in JAMA Network Open.
 

Escaping cognitive decline

Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.

“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.

To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.

The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”

The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.

The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.

To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.

Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.

At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
 

Resilience and cognitive reserve

At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.

The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.

The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).

Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).

Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).

Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.

APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.

“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.

“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.

“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
 

A ‘landmark study’

Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.

Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”

Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.

“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.

The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.

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

It is often assumed that cognitive decline is an inevitable part of aging, but a new study of centenarians suggests otherwise.

Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.

“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.

“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.

The study was published online Jan. 15 in JAMA Network Open.
 

Escaping cognitive decline

Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.

“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.

To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.

The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”

The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.

The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.

To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.

Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.

At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
 

Resilience and cognitive reserve

At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.

The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.

The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).

Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).

Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).

Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.

APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.

“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.

“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.

“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
 

A ‘landmark study’

Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.

Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”

Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.

“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.

The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.

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

It is often assumed that cognitive decline is an inevitable part of aging, but a new study of centenarians suggests otherwise.

Investigators found that despite the presence of neuropathologies associated with Alzheimer’s disease (AD), many centenarians maintained high levels of cognitive performance.

“Cognitive decline is not inevitable,” senior author Henne Holstege, PhD, assistant professor, Amsterdam Alzheimer Center and Clinical Genetics, Amsterdam University Medical Center, said in an interview.

“At 100 years or older, high levels of cognitive performance can be maintained for several years, even when individuals are exposed to risk factors associated with cognitive decline,” she said.

The study was published online Jan. 15 in JAMA Network Open.
 

Escaping cognitive decline

Dr. Holstege said her interest in researching aging and cognitive health was inspired by the “fascinating” story of Hendrikje van Andel-Schipper, who died at age 115 in 2015 “completely cognitively healthy.” Her mother, who died at age 100, also was cognitively intact at the end of her life.

“I wanted to know how it is possible that some people can completely escape all aspects of cognitive decline while reaching extreme ages,” Dr. Holstege said.

To discover the secret to cognitive health in the oldest old, Dr. Holstege initiated the 100-Plus Study, which involved a cohort of healthy centenarians.

The investigators conducted extensive neuropsychological testing and collected blood and fecal samples to examine “the myriad factors that influence physical health, including genetics, neuropathology, blood markers, and the gut microbiome, to explore the molecular and neuropsychologic constellations associated with the escape from cognitive decline.”

The goal of the research was to investigate “to what extent centenarians were able to maintain their cognitive health after study inclusion, and to what extent this was associated with genetic, physical, or neuropathological features,” she said.

The study included 330 centenarians who completed one or more neuropsychological assessments. Neuropathologic studies were available for 44 participants.

To assess baseline cognitive performance, the researchers administered a wide array of neurocognitive tests, as well as the Mini–Mental State Examination, from which mean z scores for cognitive domains were calculated.

Additional factors in the analysis included sex, age, APOE status, cognitive reserve, physical health, and whether participants lived independently.

At autopsy, amyloid-beta (A-beta) level, the level of intracellular accumulation of phosphorylated tau protein in neurofibrillary tangles (NFTs), and the neuritic plaque (NP) load were assessed.
 

Resilience and cognitive reserve

At baseline, the median age of the centenarians (n = 330, 72.4% women) was 100.5 years (interquartile range, 100.2-101.7). A little over half (56.7%) lived independently, and the majority had good vision (65%) and hearing (56.4%). Most (78.8%) were able to walk independently, and 37.9% had achieved the highest International Standard Classification of Education level of postsecondary education.

The researchers found “varying degrees of neuropathology” in the brains of the 44 donors, including A-beta, NFT, and NPs.

The duration of follow-up in analyzing cognitive trajectories ranged from 0 to 4 years (median, 1.6 years).

Assessments of all cognitive domains showed no decline, with the exception of a “slight” decrement in memory function (beta −.10 SD per year; 95% confidence interval, –.14 to –.05 SD; P < .001).

Cognitive performance was associated with factors of physical health or cognitive reserve, for example, greater independence in performing activities of daily living, as assessed by the Barthel index (beta .37 SD per year; 95% CI, .24-.49; P < .001), or higher educational level (beta .41 SD per year; 95% CI, .29-.53; P < .001).

Despite findings of neuropathologic “hallmarks” of AD post mortem in the brains of the centenarians, these were not associated with cognitive performance or rate of decline.

APOE epsilon-4 or an APOE epsilon-3 alleles also were not significantly associated with cognitive performance or decline, suggesting that the “effects of APOE alleles are exerted before the age of 100 years,” the authors noted.

“Our findings suggest that after reaching age 100 years, cognitive performance remains relatively stable during ensuing years. Therefore, these centenarians might be resilient or resistant against different risk factors of cognitive decline,” the authors wrote. They also speculate that resilience may be attributable to greater cognitive reserve.

“Our preliminary data indicate that approximately 60% of the chance to reach 100 years old is heritable. Therefore, to get a better understanding of which genetic factors associate with the prolonged maintenance of cognitive health, we are looking into which genetic variants occur more commonly in centenarians compared to younger individuals,” said Dr. Holstege.

“Of course, more research needs to be performed to get a better understanding of how such genetic elements might sustain brain health,” she added.
 

A ‘landmark study’

Commenting on the study in an interview, Thomas Perls, MD, MPH, professor of medicine, Boston University, called it a “landmark” study in research on exceptional longevity in humans.

Dr. Perls, the author of an accompanying editorial, noted that “one cannot absolutely assume a certain level or disability or risk for disease just because a person has achieved extreme age – in fact, if anything, their ability to achieve much older ages likely indicates that they have resistance or resilience to aging-related problems.”

Understanding the mechanism of the resilience could lead to treatment or prevention of AD, said Dr. Perls, who was not involved in the research.

“People have to be careful about ageist myths and attitudes and not have the ageist idea that the older you get, the sicker you get, because many individuals disprove that,” he cautioned.

The study was supported by Stichting Alzheimer Nederland and Stichting Vumc Fonds. Research from the Alzheimer Center Amsterdam is part of the neurodegeneration research program of Amsterdam Neuroscience. Dr. Holstege and Dr. Perls reported having no relevant financial relationships. The other authors’ disclosures are listed on the original article.

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

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

COVID-19 increases the risk of developing erectile dysfunction (ED) by nearly sixfold, according to data from the first study to investigate the association between ED and COVID-19 in young men in a real-life setting.

The preliminary data also indicated that ED is a marker of increased susceptibility to SARS-CoV-2 infection. Men with ED are more than five times more likely to have COVID-19 (odds ratio, 5.27).

For men with a history of COVID-19, the odds ratio of developing ED was 5.66. The strength of the association remained after adjusting for factors considered to affect ED.

The study, which was led by Emmanuele A. Jannini, MD, professor of endocrinology and medical sexology, University of Rome Tor Vergata, was published on March 20 in Andrology.
 

‘Mask up to keep it up’

ED can be both a short-term and a long-term complication of COVID-19, Dr. Jannini suggests.

“When offered, men should have the COVID vaccination. It also gives a whole new meaning to wearing the mask – mask up to keep it up,” he said. “It could possibly have the added benefit of preventing sexual dysfunction.”

He points out that older age, diabetes, high body mass index, and smoking increase the risk of contracting COVID-19.

“These are the same as risk factors for ED. Results of our study agree with the pathophysiological mechanisms linking ED, endothelial dysfunction, and COVID-19. Basically, endothelial dysfunction is common in both conditions [COVID-10 and ED].

“We would like to find some sort of biomarker of endothelial dysfunction post COVID, because it seems that there are many sequelae that coexist for a long time after infection,” added Dr. Jannini. “Asking a patient if they have ED after COVID might provide a measure of systemic wellness.”

Allan Pacey, MD, professor of andrology at the University of Sheffield (England), welcomed the research, noting, “This seems to be a well-conducted study. However, at the moment, the relationship is just a correlation, and it might be that some of the comorbidities that increased the men’s chances of getting a significant COVID-19 infection may have also independently increased their chances of erectile dysfunction.

“But the authors offer a plausible mechanism by which COVID-19 may impact directly on erectile function,” agrees Dr. Pacey. However, “There’s more work to be done,” he said. “I’d also argue it’s a good reason for men to wear a mask, practice social distancing, and take the vaccine when it’s offered to them.”

Urologist John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York, remarked, “It was a highly preliminary study, but the data are suggestive of a potential link between COVID-19 infection and ED.

“However, it raises enough questions such that further large, more long-term analyses are required to define causation. Future studies assessing testosterone levels and erectile hemodynamics will be needed to provide definite evidence of a causative link,» he stressed.
 

Erectile problems a ‘hallmark’ of systemic endothelial dysfunction

Prior research has suggested that asymptomatic COVID-19 could be associated with subclinical microvascular involvement with long-term cardiovascular effects.

“Indeed, COVID-19 is by all means an endothelial disease, in which systemic manifestations ... can potentially be due to alterations in the endothelial thrombotic/fibrinolytic balance,” emphasized Dr. Jannini. “In addition, endothelial cells express many of the cofactors used by SARS-CoV-2 to invade host cells.

“Erectile dysfunction has often been considered a hallmark of endothelial dysfunction, and as such, a potential association between ED and COVID-19 has also been postulated and underpinned the investigation in this study,” he explained.

The study was predicated on the fact that ED is often considered a clinical marker of impaired overall health status, which often features cardiovascular events at an early age. It aimed to investigate the bidirectional relationship between COVID-19 and ED. It asked whether ED could be a risk factor for contracting COVID-19 and whether having COVID-19 predisposes to developing ED.

“This would possibly suggest that men with ED, due to the underlying conditions which impair erectile response, could also be more susceptible to contracting COVID-19,” said Dr. Jannini.

Data were drawn from the Sex@COVID online survey, which was conducted from April 7 to May 4, 2020, in Italy. The survey included 6,821 participants aged 18 years or older (4,177 women; 2,644 men; mean age, 32.83 ± 11.24 years). Participants were stratified on the basis of marital status and sexual activity during lockdown. From these participants, 985 sexually active men were identified, among whom 25 (2.54%) reported having tested positive for COVID-19. These persons were matched with 75 COVID-19–negative men using propensity score matching in a 1:3 ratio.

The researchers used standardized psychometric tools to measure the effects of lockdown and social distancing on the intrapsychic, relational, and sexual health of the participants.

Erectile function was measured with the International Index of Erectile Function or the Sexual Health Inventory for Men, which are often used in clinical settings. In light of the two-way interaction between sexual activity and psychological well-being, results were adjusted for any influence of anxiety and depression, which were measured with recognized scales for use in patients with a history of COVID-19.

Results showed that the prevalence of ED was significantly higher among men who self-reported a history of COVID-19, compared with a matching COVID-negative population (28% vs. 9.33%; P = .027).

After adjusting for variables that are considered to have a bearing on the development of ED, such as psychological status, age, and BMI, the odds ratio for developing ED after having had COVID-19 was 5.66 (95% confidence interval, 1.50-24.01).

Similarly, after adjusting for age and BMI, men with ED were more likely to have COVID‐19 (OR, 5.27; 95% CI, 1.49-20.09).

The authors note that persons who experience “a sudden onset or worsening of ED might also consider precautionary quarantine or nasopharyngeal swab, as COVID‐19 might act as a potential initiating trigger for the onset of erectile impairment, or an aggravating factor for its progression to more severe forms.”

Similarly, patients who have ED “should consider their erectile impairment as a sign of possible underlying conditions that could increase the likelihood of suffering from COVID‐19,” they write.

Dr. Mulhall highlighted several limitations of the study, including its retrospective nature, recall bias associated with the use of online questionnaires, and the inclusion of COVID‐19 diagnoses that were based on the response to the survey rather than on testing with nasopharyngeal swabs. In addition, comorbidity data were incomplete, and there was no indication of duration after COVID-19 infection, the severity of COVID-19, or the severity of ED.

The authors have disclosed no relevant financial relationships. Dr. Pacey is chairman of the advisory committee of the U.K. National External Quality Assurance Schemes in Andrology, editor-in-chief of Human Fertility, trustee of the Progress Educational Trust, and trustee of the British Fertility Society (all unpaid). Dr. Mulhall has disclosed no relevant financial relationships.

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

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

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

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

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

Cardiovascular and metabolic risk factors are increased among transgender youths, compared with youths who are not transgender. Elevations in lipid levels and body mass index (BMI) also occur in adult transgender patients, new research shows.

“This is the first study of its size in the United States of which we are aware that looks at the odds of youth with a diagnosis of gender dysphoria having medical diagnoses that relate to overall metabolic and cardiovascular health,” first author Anna Valentine, MD, of Children’s Hospital Colorado, Aurora, said in a press statement.

Although previous studies have shown that among transgender adults, BMI is higher and there is an increased risk for cardiovascular events, such as stroke or heart attack, compared with nontransgender people, research on adolescent transgender patients has been lacking.

With a recent survey showing that nearly 2% of adolescents identify as transgender, interest in health outcomes among younger patients is high.

To investigate, Dr. Valentine, and colleagues evaluated data from the PEDSnet pediatric database on 4,177 youths who had received a diagnosis of gender dysphoria. The participants had been enrolled at six sites from 2009 to 2019. The researchers compared these patients in a ratio of 1:4 with 16,664 control persons who had not been diagnosed with gender dysphoria. They reported their findings as a poster at the annual meeting of the Endocrine Society.

For the propensity-score analysis, participants were matched according to year of birth, age at last visit, site, race, ethnicity, insurance status, and duration in the database.

In both the transgender and control groups, about 66% were female at birth, 73% were White, and 9% Hispanic. For both groups, the average age was 16.2 years at the last visit. The average duration in the database was 7 years.
 

Study didn’t distinguish between those receiving and those not receiving gender-affirming hormones

In the retrospective study, among those who identified as transgender, the rates of diagnoses of dyslipidemia (odds ratio, 1.6; P < .0001) and metabolic syndrome (OR, 1.9; P = .0086) were significantly higher, compared with those without gender dysphoria.

Among the transgender male patients (born female) but not transgender female patients (born male), rates of diagnoses of overweight/obesity (OR, 1.7; P < .0001) and polycystic ovary syndrome were higher (OR, 1.9, P = .0006), compared with controls.

Gender-affirming hormone therapy, such as with testosterone or estradiol, is among the suspected culprits for the cardiovascular effects. However, importantly, this study did not differentiate between patients who had received estradiol or testosterone for gender affirmation and those who had not, Dr. Valentine said.

“We don’t know [whether gender-affirming hormone therapy is a cause], as we have not looked at this yet,” she said in an interview. “We are looking at that in our next analyses and will be including that in our future publication.

“We’ll also be looking at the relationship between having overweight/obesity and the other diagnoses that influence cardiovascular health (high blood pressure, liver dysfunction, and abnormal cholesterol), as that could certainly be playing a role as well,” she said.

For many transgender patients, gender-affirming hormone therapy is lifelong. One question that needs to be evaluated concerns whether the dose of such therapy has a role on cardiovascular effects and if so, whether adjustments could be made without compromising the therapeutic effect, Dr. Valentine noted.

“This is an important question, and future research is needed to evaluate whether doses [of gender-affirming hormones] are related to cardiometabolic outcomes,” she said.

Potential confounders in the study include the fact that rates of overweight and obesity are higher among youths with gender dysphoria. This can in itself can increase the risk for other disorders, Dr. Valentine noted.

Furthermore, rates of mental health comorbidities are higher among youths with gender dysphoria. One consequence of this may be that they engage in less physical activity, she said.
 

Hormone therapy, health care disparities, or both could explain risk

In commenting on the study, Joshua D. Safer, MD, executive director of the Center for Transgender Medicine and Surgery, the Mount Sinai Health System, New York, said that although similar cardiovascular effects are known to occur in transgender adults as well, they may or may not be hormone related. Other factors can increase the risk.

“With transgender adults, any differences in lipids or cardiac risk factors relative to cisgender people might be attributable either to hormone therapy or to health care disparities,” he said in an interview.

“The data are mixed. It may be that most differences relate to lack of access to care and to mistreatment by society,” he said. “Even studies that focus on hormones see a worsened situation for trans women versus trans men.”

Other recent research that shows potential cardiovascular effects among adult transgender men includes a study of more than 1,000 transgender men (born female) who received testosterone. That study, which was also presented at the ENDO meeting and was reported by this news organization, found an increased risk for high hematocrit levels, which could lead to a thrombotic event.

However, a study published in Pediatrics, which was also reported by this news organization, that included 611 transgender youths who had taken gender-affirming hormone therapy for more than a year found no increased risk for thrombosis, even in the presence of thrombosis risk factors, including obesity, tobacco use, and family history of thrombosis. However, the senior author of that study pointed out that the duration of follow-up in that study was relatively short, which may have been why they did not find an increased risk for thrombosis.

Dr. Safer noted that transgender youths and adults alike face a host of cultural factors that could play a role in increased cardiovascular risks.

“For adults, the major candidate explanations for worse BMI and cardiac risk factors are societal mistreatment, and for trans women specifically, progestins. For youth, the major candidate explanations are societal mistreatment and lack of access to athletics,” he said.

The authors and Dr. Safer disclosed no relevant financial relationships.

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

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

Patients being treated with infliximab had weakened immune responses to the first dose of the ChAdOx1 nCoV-19 (Oxford/AstraZeneca) and BNT162b2 (Pfizer/BioNTech) vaccines, compared with patients on vedolizumab (Entyvio), although a very significant number of patients from both groups seroconverted after their second dose, according to a new U.K. study of patients with inflammatory bowel disease (IBD).

NoSystem images/Getty Images

“Antibody testing and adapted vaccine schedules should be considered to protect these at-risk patients,” Nicholas A. Kennedy, PhD, MBBS, of the University of Exeter (England) and colleagues wrote in a preprint published March 29 on MedRxiv.

Infliximab is an anti–tumor necrosis factor (anti-TNF) monoclonal antibody that’s approved to treat adult and pediatric Crohn’s disease and ulcerative colitis, as well as rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and plaque psoriasis, whereas vedolizumab, a gut selective anti-integrin alpha4beta7 monoclonal antibody that is not associated with impaired systemic immune responses, is approved to treat Crohn’s disease and ulcerative colitis in adults.

A previous study from Kennedy and colleagues revealed that IBD patients on infliximab showed a weakened COVID-19 antibody response compared with patients on vedolizumab. To determine if treatment with anti-TNF drugs impacted the efficacy of the first shot of these two-dose COVID-19 vaccines, the researchers used data from the CLARITY IBD study to assess 865 infliximab- and 428 vedolizumab-treated participants without evidence of prior SARS-CoV-2 infection who had received uninterrupted biologic therapy since being recruited between Sept. 22 and Dec. 23, 2020.

In the 3-10 weeks after initial vaccination, geometric mean concentrations for SARS-CoV-2 anti-spike protein receptor-binding protein antibodies were lower in patients on infliximab, compared with patients on vedolizumab for both the Pfizer (6.0 U/mL [5.9] versus 28.8 U/mL [5.4], P < .0001) and AstraZeneca (4.7 U/mL [4.9] versus 13.8 U/mL [5.9]; P < .0001) vaccines. The researchers’ multivariable models reinforced those findings, with antibody concentrations lower in infliximab-treated patients for both the Pfizer (fold change, 0.29; 95% confidence interval, 0.21-0.40; P < .0001) and AstraZeneca (FC, 0.39; 95% CI, 0.30-0.51; P < .0001) vaccines.

After second doses of the two-dose Pfizer vaccine, 85% of patients on infliximab and 86% of patients on vedolizumab seroconverted (P = .68); similarly high seroconversion rates were seen in patients who had been infected with SARS-CoV-2 prior to receiving either vaccine. Several patient characteristics were associated with lower antibody concentrations regardless of vaccine type: being 60 years or older, use of immunomodulators, having Crohn’s disease, and being a smoker. Alternatively, non-White ethnicity was associated with higher antibody concentrations.

Evidence has ‘unclear clinical significance’

“These data, which require peer review, do not change my opinion on the safety and efficacy of COVID-19 vaccines in patients taking TNF inhibitors such as infliximab as monotherapy for the treatment of psoriatic disease,” Joel M. Gelfand MD, director of the psoriasis and phototherapy treatment center at the University of Pennsylvania, Philadelphia, said in an interview.

Courtesy Dr. Joel M. Gelfand

“First, two peer-reviewed studies found good antibody response in patients on TNF inhibitors receiving COVID-19 vaccines (doi: 10.1136/annrheumdis-2021-220289; 10.1136/annrheumdis-2021-220272). Second, antibody responses were robust in the small cohort that received the second dose of a COVID-19 vaccine. We already know that, for the two messenger RNA-based vaccines available under emergency use authorization in the U.S., a second dose is required for optimal efficacy. Thus, evidence of a reduced antibody response after just one dose is of unclear clinical significance. Third, antibody responses are only a surrogate marker, and a low antibody response doesn’t necessarily mean the patient will not be protected by the vaccine.”
 

Focus on the second dose of a two-dose regimen

“Tell me about the response in people who got both doses of a vaccine that you’re supposed to get both doses of,” Jeffrey Curtis, MD, professor of medicine in the division of clinical immunology and rheumatology at the University of Alabama at Birmingham, said in an interview. “The number of patients in that subset was small [n = 27] but in my opinion that’s the most clinically relevant analysis and the one that patients and clinicians want answered.”

Courtesy UAB Photo

He also emphasized the uncertainty around what ‘protection’ means in these early days of studying COVID-19 vaccine responses. “You can define seroprotection or seroconversion as some absolute level of an antibody response, but if you want to say ‘Mrs. Smith, your antibody level was X,’ on whatever arbitrary scale with whoever’s arbitrary lab test, nobody actually knows that Mrs. Smith is now protected from SARS-CoV-2, or how protected,” he said.

“What is not terribly controversial is: If you can’t detect antibodies, the vaccine didn’t ‘take,’ if you will. But if I tell you that the mean antibody level was X with one drug and then 2X with another drug, does that mean that you’re twice as protected? We don’t know that. I’m fearful that people are looking at these studies and thinking that more is better. It might be, but we don’t know that to be true.”
 

Debating the cause of weakened immune responses

“The biological plausibility of being on an anti-TNF affecting your immune reaction to a messenger RNA or even a replication-deficient viral vector vaccine doesn’t make sense,” David T. Rubin, MD, professor of medicine at the University of Chicago and chair of the National Scientific Advisory Committee of the Crohn’s and Colitis Foundation, said in an interview.

“I’m sure immunologists may differ with me on this, but given what we have come to appreciate about these vaccine mechanisms, this finding doesn’t make intuitive sense. So we need to make sure that, when this happens, we look to the next studies and try to understand, was there any other confounder that may have resulted in these findings that was not adequately adjusted for or addressed in some other way?

“When you have a study of this size, you argue, ‘Because it’s so large, any effect that was seen must be real,’ ” he added. “Alternatively, to have a study of this size, by its very nature you are limited in being able to control for certain other factors or differences between the groups.”

That said, he commended the authors for their study and acknowledged the potential questions it raises about the single-shot Johnson & Johnson vaccine. “If you only get one and you’re on infliximab, this study implies that maybe that’s not enough,” he said. “Despite the fact that Johnson & Johnson was approved as a single dose, it may be necessary to think about it as the first of two, or maybe it’s not the preferred vaccine in this group of patients.”

The study was supported by the Royal Devon and Exeter and Hull University Hospital Foundation NHS Trusts and unrestricted educational grants from Biogen (Switzerland), Celltrion Healthcare (South Korea), Galapagos NV (Belgium), and F. Hoffmann-La Roche (Switzerland). The authors acknowledged numerous potential conflicts of interest, including receiving grants, personal fees, and nonfinancial support from various pharmaceutical companies.

The incidence of venous thromboembolism (VTE) in nonhospitalized patients with COVID-19 was not significantly different from patients without the infectious disease, according to a new study published in JAMA Internal Medicine.

Design Cells/Getty Images

National Institutes of Health guidelines recommend blood thinners to prevent blood clots in patients hospitalized with COVID-19. However, the new study provides more insight on the best treatment approach for COVID-19 outpatients.

“[COVID-19’s] rapid global progression and impact has caused us to make and modify treatment decisions at a pace that we never have in modern medicine,” study author Nareg Roubinian, MD, an investigator at Kaiser Permanente, Oakland, Calif., said in an interview.

“As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes,” Dr. Roubinian added.

The increased risk of blood clots in patients hospitalized with COVID-19 has been a major issue throughout the pandemic. In fact, one study published in November 2020 found that more than half of patients hospitalized with the illness have prothrombotic antiphospholipid (aPL) autoantibodies in their blood, which could contribute to venous and arterial thromboembolism.

Although it was clear many hospitalized patients diagnosed with COVID-19 were developing more clots, researchers of the current study were not sure if this trend would also be seen in outpatients.

“Most people with COVID-19 do not need to be hospitalized, and we needed to know how often patients outside the hospital were having blood clots,” said Dr. Roubinian.

For the study, Dr. Roubinian and colleagues examined data on 220,588 patients who were members of Kaiser Permanente Northern California health plan and were tested for COVID-19 between Feb. 25 and Aug. 31, 2020. They then reported on the 30-day incidence of outpatient and hospital-associated blood clots following the COVID-19 diagnosis. Patients who were asymptomatic at the time of testing or had received anticoagulants within the last year were excluded.

“We knew from other studies that patients with COVID-19 often get sicker in the first few weeks after infection. What we didn’t know was whether COVID-19 patients were developing blood clots but not pneumonia or were developing blood clots at the same time as they developed pneumonia,” said Dr. Roubinian, an intensive care doctor with the Permanente Medical Group in Oakland, Calif. “Following the patients for 30 days allowed us to focus on the time period from infection to when blood clots were most likely to develop.”

Researchers found that of the cohort who took the COVID-19 test, 11.8% had a positive result. Within 30 days of the COVID-19 test, 0.8% of patients with a positive result were diagnosed with VTE compared to 0.5% of those who received a negative test result. They also found that viral testing took place in an outpatient setting for 59.1% of the patients with a positive viral test who later developed VTE. Of those patients, 76.1% had to be hospitalized.

Dr. Roubinian said he was surprised to see that the blood clotting in outpatients with COVID-19 was similar in frequency to what he saw in patients without the infection.

“Our findings suggest that blood clots do occur in COVID-19 patients but not on a scale where we need to put all or many COVID outpatients on blood thinners,” he said. “As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes.”

In December 2020, three trials investigating the risk and benefits of increased levels of anticoagulation in hospitalized COVID-19 patients were paused because of safety issues. The trials would have enrolled critically ill COVID-19 patients for whom therapeutic doses of anticoagulation drugs showed no benefit.

Anticoagulants are associated with bleeding risks, including prolonged nosebleeds and vomiting or coughing up blood.

Instead of prescribing the routine use of thromboprophylactic drugs to COVID-19 outpatients, Dr. Roubinian believes it would be helpful to learn how to determine whether a patient at risk of becoming sick or being hospitalized would benefit from being treated with such drugs.

Dr. Roubinian reported receiving grants from the National Institutes of Health and the National Heart, Lung, and Blood Institute during the conduct of the study.
 

The incidence of venous thromboembolism (VTE) in nonhospitalized patients with COVID-19 was not significantly different from patients without the infectious disease, according to a new study published in JAMA Internal Medicine.

Design Cells/Getty Images

National Institutes of Health guidelines recommend blood thinners to prevent blood clots in patients hospitalized with COVID-19. However, the new study provides more insight on the best treatment approach for COVID-19 outpatients.

“[COVID-19’s] rapid global progression and impact has caused us to make and modify treatment decisions at a pace that we never have in modern medicine,” study author Nareg Roubinian, MD, an investigator at Kaiser Permanente, Oakland, Calif., said in an interview.

“As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes,” Dr. Roubinian added.

The increased risk of blood clots in patients hospitalized with COVID-19 has been a major issue throughout the pandemic. In fact, one study published in November 2020 found that more than half of patients hospitalized with the illness have prothrombotic antiphospholipid (aPL) autoantibodies in their blood, which could contribute to venous and arterial thromboembolism.

Although it was clear many hospitalized patients diagnosed with COVID-19 were developing more clots, researchers of the current study were not sure if this trend would also be seen in outpatients.

“Most people with COVID-19 do not need to be hospitalized, and we needed to know how often patients outside the hospital were having blood clots,” said Dr. Roubinian.

For the study, Dr. Roubinian and colleagues examined data on 220,588 patients who were members of Kaiser Permanente Northern California health plan and were tested for COVID-19 between Feb. 25 and Aug. 31, 2020. They then reported on the 30-day incidence of outpatient and hospital-associated blood clots following the COVID-19 diagnosis. Patients who were asymptomatic at the time of testing or had received anticoagulants within the last year were excluded.

“We knew from other studies that patients with COVID-19 often get sicker in the first few weeks after infection. What we didn’t know was whether COVID-19 patients were developing blood clots but not pneumonia or were developing blood clots at the same time as they developed pneumonia,” said Dr. Roubinian, an intensive care doctor with the Permanente Medical Group in Oakland, Calif. “Following the patients for 30 days allowed us to focus on the time period from infection to when blood clots were most likely to develop.”

Researchers found that of the cohort who took the COVID-19 test, 11.8% had a positive result. Within 30 days of the COVID-19 test, 0.8% of patients with a positive result were diagnosed with VTE compared to 0.5% of those who received a negative test result. They also found that viral testing took place in an outpatient setting for 59.1% of the patients with a positive viral test who later developed VTE. Of those patients, 76.1% had to be hospitalized.

Dr. Roubinian said he was surprised to see that the blood clotting in outpatients with COVID-19 was similar in frequency to what he saw in patients without the infection.

“Our findings suggest that blood clots do occur in COVID-19 patients but not on a scale where we need to put all or many COVID outpatients on blood thinners,” he said. “As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes.”

In December 2020, three trials investigating the risk and benefits of increased levels of anticoagulation in hospitalized COVID-19 patients were paused because of safety issues. The trials would have enrolled critically ill COVID-19 patients for whom therapeutic doses of anticoagulation drugs showed no benefit.

Anticoagulants are associated with bleeding risks, including prolonged nosebleeds and vomiting or coughing up blood.

Instead of prescribing the routine use of thromboprophylactic drugs to COVID-19 outpatients, Dr. Roubinian believes it would be helpful to learn how to determine whether a patient at risk of becoming sick or being hospitalized would benefit from being treated with such drugs.

Dr. Roubinian reported receiving grants from the National Institutes of Health and the National Heart, Lung, and Blood Institute during the conduct of the study.
 

The incidence of venous thromboembolism (VTE) in nonhospitalized patients with COVID-19 was not significantly different from patients without the infectious disease, according to a new study published in JAMA Internal Medicine.

Design Cells/Getty Images

National Institutes of Health guidelines recommend blood thinners to prevent blood clots in patients hospitalized with COVID-19. However, the new study provides more insight on the best treatment approach for COVID-19 outpatients.

“[COVID-19’s] rapid global progression and impact has caused us to make and modify treatment decisions at a pace that we never have in modern medicine,” study author Nareg Roubinian, MD, an investigator at Kaiser Permanente, Oakland, Calif., said in an interview.

“As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes,” Dr. Roubinian added.

The increased risk of blood clots in patients hospitalized with COVID-19 has been a major issue throughout the pandemic. In fact, one study published in November 2020 found that more than half of patients hospitalized with the illness have prothrombotic antiphospholipid (aPL) autoantibodies in their blood, which could contribute to venous and arterial thromboembolism.

Although it was clear many hospitalized patients diagnosed with COVID-19 were developing more clots, researchers of the current study were not sure if this trend would also be seen in outpatients.

“Most people with COVID-19 do not need to be hospitalized, and we needed to know how often patients outside the hospital were having blood clots,” said Dr. Roubinian.

For the study, Dr. Roubinian and colleagues examined data on 220,588 patients who were members of Kaiser Permanente Northern California health plan and were tested for COVID-19 between Feb. 25 and Aug. 31, 2020. They then reported on the 30-day incidence of outpatient and hospital-associated blood clots following the COVID-19 diagnosis. Patients who were asymptomatic at the time of testing or had received anticoagulants within the last year were excluded.

“We knew from other studies that patients with COVID-19 often get sicker in the first few weeks after infection. What we didn’t know was whether COVID-19 patients were developing blood clots but not pneumonia or were developing blood clots at the same time as they developed pneumonia,” said Dr. Roubinian, an intensive care doctor with the Permanente Medical Group in Oakland, Calif. “Following the patients for 30 days allowed us to focus on the time period from infection to when blood clots were most likely to develop.”

Researchers found that of the cohort who took the COVID-19 test, 11.8% had a positive result. Within 30 days of the COVID-19 test, 0.8% of patients with a positive result were diagnosed with VTE compared to 0.5% of those who received a negative test result. They also found that viral testing took place in an outpatient setting for 59.1% of the patients with a positive viral test who later developed VTE. Of those patients, 76.1% had to be hospitalized.

Dr. Roubinian said he was surprised to see that the blood clotting in outpatients with COVID-19 was similar in frequency to what he saw in patients without the infection.

“Our findings suggest that blood clots do occur in COVID-19 patients but not on a scale where we need to put all or many COVID outpatients on blood thinners,” he said. “As with other potential therapies for COVID-19, blood thinners need to be prospectively studied in a clinical trial to determine if they improve patient outcomes.”

In December 2020, three trials investigating the risk and benefits of increased levels of anticoagulation in hospitalized COVID-19 patients were paused because of safety issues. The trials would have enrolled critically ill COVID-19 patients for whom therapeutic doses of anticoagulation drugs showed no benefit.

Anticoagulants are associated with bleeding risks, including prolonged nosebleeds and vomiting or coughing up blood.

Instead of prescribing the routine use of thromboprophylactic drugs to COVID-19 outpatients, Dr. Roubinian believes it would be helpful to learn how to determine whether a patient at risk of becoming sick or being hospitalized would benefit from being treated with such drugs.

Dr. Roubinian reported receiving grants from the National Institutes of Health and the National Heart, Lung, and Blood Institute during the conduct of the study.