MDedge Infectious Disease

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

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

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

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

COVID-19 infection during pregnancy has been linked to a small but significant effect on infant neurodevelopment, suggests a small-scale analysis that points to the need for further study and monitoring during pregnancy.

The study included 24 pregnant women, half of whom had COVID-19 during pregnancy, and their offspring. It showed impairments at 6 weeks of age on the social interactive dimension of a neonatal assessment.

“Not all babies born to mothers infected with COVID show neurodevelopmental differences, but our data show that their risk is increased in comparison to those not exposed to COVID in the womb. We need a bigger study to confirm the exact extent of the difference,” said lead researcher Rosa Ayesa Arriola, PhD, Valdecilla Research Institute (IDIVAL), Hospital Universitario Marqués de Valdecilla, Santander, Spain, in a release.

The findings were presented at the virtual European Psychiatric Association 2022 Congress.
 

Differing responses to cuddling

Coauthor Águeda Castro Quintas, PhD student, Network Centre for Biomedical Research in Mental Health, University of Barcelona, explained that the tests showed the children born to mothers who had COVID-19 during pregnancy reacted “slightly differently to being held, or cuddled.”

“We need to note that these are preliminary results, but this is part of a project following a larger sample of 100 mothers and their babies,” she added. The authors plan to compare their results with those from a similar study.

The group will also monitor infant language and motor development aged between 18 and 42 months.

“This is an ongoing project, and we are at an early stage,” Ms. Castro Quintas said. “We don’t know if these effects will result in any longer-term issues,” but longer-term observation “may help us understand this.”

“Of course, in babies who are so young, there are several things we just can’t measure, such as language skills or cognition,” added coinvestigator Nerea San Martín González, department of evolutionary biology, ecology and environmental sciences, University of Barcelona.

While emphasizing the need for larger sample sizes, she said that “in the meantime, we need to stress the importance of medical monitoring to facilitate a healthy pregnancy.”

The researchers note that the consequences of the COVID-19 pandemic for the newborns of affected mothers remain “unknown.”

However, previous studies of other infections during pregnancy suggest that offspring could be “especially vulnerable,”as the pathophysiological mechanisms of the infection, such as cytokine storms and microcoagulation, “could clearly compromise fetal neurodevelopment.”

To investigate further, they examined the neurodevelopment of infants born both immediately before and during the COVID-19 pandemic, from 2017 to 2021.

Twenty-one women who had COVID-19 during pregnancy were matched with 21 healthy controls. They were studied both during pregnancy and in the postpartum period, completing hormonal and other biochemical tests, salivary tests, movement assessments, and psychological questionnaires, adjusted for various factors.

The team also administered the Brazelton Neonatal Behavioural Assessment Scale (NBAS) to the offspring at 6 weeks of age to evaluate neurologic, social, and behavioral aspects of function.

“We have been especially sensitive in how we have conducted these tests,” said Ms. Castro Quintas. “Each mother and baby were closely examined by clinicians with expert training in the field and in the tests.”

Among those offspring exposed to COVID-19 during pregnancy, there was a significant decrease in scores on the social interactive dimension of the NBAS, particularly if infection occurred before week 20 of gestation.

Other NBAS subscales were not associated with maternal COVID-19 during pregnancy.
 

More research needed

Commenting on the findings, Livio Provenzi, PhD, a psychologist and researcher in developmental psychobiology at the University of Pavia (Italy), noted there is a “great need” to study the direct and indirect effect of the COVID-19 pandemic on parents and their children. “Pregnancy is a period of life which shapes much of our subsequent development, and exposure to adversity in pregnancy can leave long-lasting biological footprints.”

Dr. Provenzi, who was not involved in the study, added in the release that the findings reinforce “evidence of epigenetic alterations in infants born from mothers exposed to pandemic-related stress during pregnancy.

“It shows we need more large-scale, international research to allow us to understand the developmental effects of this health emergency and to deliver better quality of care to parents and infants.”

The study was funded by the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III through the University of Barcelona multicenter project and the Government of Cantabria. No relevant financial relationships were declared.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

If you have bacteria in your urine but don’t have symptoms of a urinary tract infection (UTI), such as burning or frequent urination, you probably don’t need antibiotics. So why did you get that prescription?

The Infectious Diseases Society of America recommends against antibiotics in this scenario, with exceptions for patients who are pregnant or undergoing certain urologic procedures.

Antibiotics for asymptomatic bacteriuria (ASB) generally do not help; are costly; and can cause side effects, Clostridioides difficile infection, and antibiotic resistance.

Still, antibiotic treatment for asymptomatic bacteriuria remains common, despite guidelines.

And when researchers recently surveyed 551 primary care clinicians to see which ones would inappropriately prescribe antibiotics for a positive urine culture, the answer was most of them: 71%.

“Regardless of years in practice, training background, or professional degree, most clinicians indicated that they would prescribe antibiotics for asymptomatic bacteriuria,” the researchers reported in JAMA Network Open.

Some groups of clinicians seemed especially likely to prescribe antibiotics unnecessarily.

“Medical maximizers” – clinicians who prefer treatment even when its value is ambiguous – and family medicine clinicians were more likely to prescribe antibiotics in response to a hypothetical case.

What to do for Mr. Williams?

To examine clinician attitudes and characteristics associated with prescribing antibiotics for asymptomatic bacteriuria, Dr. Baghdadi and his colleagues analyzed survey responses from 490 physicians and 61 advanced practice clinicians.

Study participants completed tests that measure numeracy, risk-taking preferences, burnout, and tendency to maximize care. They were presented with four hypothetical clinical scenarios, including a case of asymptomatic bacteriuria: “Mr. Williams, a 65-year-old man, comes to the office for follow-up of his osteoarthritis. He has noted foul-smelling urine and no pain or difficulty with urination. A urine dipstick shows trace blood. He has no particular preference for testing and wants your advice.”

Clinicians who had been in practice for at least 10 years were more likely to prescribe antibiotics (82%) to “Mr. Williams” than were those with 3-9 years in practice (73%) or less than 3 years in practice (64%).

Breaking a habit

Some prescribers may know not to treat asymptomatic bacteriuria but mistakenly consider certain findings to be symptoms of UTI.

Bradley Langford, PharmD, an antimicrobial stewardship expert with Public Health Ontario, said in his experience, most clinicians who say they know not to treat ASB incorrectly believe that cloudy urine, altered cognition, and other nonspecific symptoms indicate a UTI.

“The fact that most clinicians would treat ASB suggests that there is still a lot of work to do to improve antimicrobial stewardship, particularly outside of the hospital setting,” Dr. Langford told this news organization.

Avoiding unnecessary antibiotics is important not just because of the lack of benefit, but also because of the potential harms, said Dr. Langford. He has created a list of rebuttals for commonly given reasons for testing and treating asymptomatic bacteriuria.

“Using antibiotics for ASB can counterintuitively increase the risk for symptomatic UTI due to the disruption of protective local microflora, allowing for the growth of more pathogenic/resistant organisms,” he said.

One approach to addressing the problem: Don’t test urine in the first place if patients are asymptomatic. Virtual learning sessions have been shown to reduce urine culturing and urinary antibiotic prescribing in long-term care homes, Dr. Langford noted.

Updated training for health care professionals from the outset may also be key, and the lower rate of prescribing intent among resident physicians is reassuring, he said.
 

A role for patients

Patients could also help decrease the inappropriate use of antibiotics.

“Be clear with your doctor about your expectations for the health care interaction, including whether you are expecting to receive antibiotics,” Dr. Baghdadi said. “Your doctor may assume you contacted them because you wanted a prescription. If you are not expecting antibiotics, you should feel free to say so. And if you are asymptomatic, you may not need antibiotics, even if the urine culture is positive.”

The study was funded by a grant from the National Institutes of Health, and Dr. Baghdadi received grant support from the University of Maryland, Baltimore Institute for Clinical and Translational Research. Coauthors disclosed government grants and ties to Memorial Sloan Kettering Cancer Center, Vedanta Biosciences, Opentrons, and Fimbrion. Dr. Langford reported no relevant financial conflicts of interest.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

Actions taken against a physician’s license for substance use are more common than those for psychological impairment or actions related to physical health, according to a recent report. Despite a sharp uptick in 2011, substance use–specific license actions taken against physicians dropped in frequency between 2004 and 2020.

More than three fourths (76.3%) of license actions taken against physicians were related to substance use, according to a recent study published in JAMA. Psychological impairment was the reason associated with more than 1 in 10 (11.5%) actions taken against physicians’ licenses, while physical impairment was the reason behind approximately 12% of such actions, per the study.

Researchers analyzed 5032 actions taken against the licenses of U.S. physicians. The actions were reported to the National Practitioner Data Bank and were related to substance use, psychological impairment, and physical impairment. The National Practitioner Data Bank is a web-based repository of reports with information on medical malpractice payments and certain adverse actions related to healthcare practitioners, providers, and suppliers. It is provided by the Department of Health & Human Services.

“While there has been increased attention [on] the mental health of physicians, we wanted to understand the extent to which changes in attitudes and practices were reflected in actions taken by hospitals or licensing boards, which are reported in the National Practitioner Data Bank,” Lisa Rotenstein, MD, a primary care physician at Boston’s Brigham and Women’s Hospital and lead author of the study, told this news organization.

Dr. Rotenstein, who is an assistant professor at Harvard Medical School, Boston, studies issues of mental health among physicians and trainees. Dr. Rotenstein was the lead author of a 2016 study that found that more than a quarter (27.2%) of medical students have depressive symptoms. She was also lead author of a 2018 study published in JAMA on the prevalence of burnout among attending physicians.
 

Actions against physicians trending downward

2011 marked the peak in actions taken against physicians’ licenses for substance use, per the study, but actions related to substance use have otherwise maintained a steady decline over the past 17 years. Researchers found that physicians with license actions as a result of substance use or psychological impairment were more likely to receive indefinite penalties, while also having emergency action taken against their license to practice.

In addition, physicians who had actions taken against their licenses because of substance use or psychological impairment were more likely to accrue a greater number of actions over the course of their careers, according to the study.

About 47% of physicians reported experiencing burnout per Medscape’s Physician Burnout and Depression Report 2022: Stress, Anxiety, and Anger report. Burnout among emergency physicians spiked from 43% in 2020 to 60% in 2021, according to the report.

More than one quarter (26%) of physicians reported drinking alcohol to cope with burnout in 2020, according to Medscape’s 2021 Physician Burnout and Suicide Report. Per the 2021 report, 48% of physicians chose exercise to deal with burnout, while 35% indulged in eating junk food.

Peter Grinspoon, MD, a Boston-based primary care physician, wrote in The Los Angeles Times in 2016 that the rate of substance abuse among physicians starts at 10% and can go as high as 15%; by comparison, rates of substance use among the general population are 8%-10%. “What appears to account for the difference is physician distress, and in the case of drug abuse, plentiful access,” he added.

Dr. Grinspoon wrote a 2016 book called “Free Refills: A Doctor Confronts His Addiction,” which chronicles his experience in recovery and relapse as a physician who was dependent on opioid painkillers.

The findings from the recent study in JAMA “suggest we have made some progress in addressing issues related to substance use in ways that don’t result in license actions or even in meeting physicians’ need for support related to substance use,” said Dr. Rotenstein.

Still, she insists that there’s “substantial opportunity to improve mental health and support offerings for physicians and to reduce stigma related to seeking and receiving mental health support, ideally averting the need for license actions.”

According to Dr. Rotenstein, the cases listed in the National Practitioner Data Bank represent the most severe cases; these reports have risen to a high level of attention or concern and are the result of adverse action reports submitted by healthcare institutions and state licensing boards.

“There are many, many more physicians whose cases are not represented here but who struggle with depression, anxiety, substance use, and more,” said Dr. Rotenstein.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

A federal advisory panel strongly supported a bid for Novavax to win U.S. emergency authorization for its COVID-19 vaccine, which is based on a more traditional, protein-based approach than the cutting-edge technology used in mRNA-based shots.

The Vaccines and Related Biological Products Advisory Committee of the Food and Drug Administration voted almost unanimously June 7 in favor of Novavax’s two-dose COVID-19 vaccine for those 18 or older – despite some concerns over rare events of myocarditis and pericarditis.

The tally was 21 “yes” votes, without any “no” votes, but one abstention from a panelist who then offered a largely positive take on this vaccine.

Panelist Bruce Gellin, MD, explained at the end of the meeting that he would have cast a conditional vote in favor of the Novavax vaccine, called NVX-CoV2373, had that been an option. Dr. Gellin, chief of global public health strategy for the Rockefeller Foundation and a vaccine expert, said he didn’t want his abstention to be considered as signaling opposition to the Novavax shot.

Instead, he said, he expects FDA officials will gather more data and evidence about the Novavax vaccine, especially in relation to certain manufacturing issues, before making its decision on the company’s application.

Earlier in the day, a top FDA vaccine reviewer, Doran Fink, MD, PhD, noted that there were important manufacturing differences between the Novavax vaccine supply used in different projects, complicating efforts to assess the company’s application for emergency use authorization (EUA).

But Dr. Fink noted that the FDA staff already had made a convincing case in its briefing document, with enough evidence for an initial conditional clearance to be found in available data.

The FDA is not bound to follow the suggestions of its advisory committees but it often does.
 

Using the ‘bully pulpit’

At the beginning of the meeting, Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said he was seizing the “bully pulpit” in addressing the need to persuade more people in the United States to take shots against COVID-19.

About 67% of people in the United States aged 18 and older are fully vaccinated, but only about 50% of those in this group have had a first booster, according to the Centers for Disease Control and Prevention.

The two-dose mRNA vaccines from Pfizer and Moderna have been the subject of intense misinformation campaigns on social media, despite efforts by the FDA and other public health officials to convey the message about their strong benefit-risk profile. The FDA in May limited the authorized use of Johnson & Johnson’s single-dose COVID-19 shot, which is based on a different technology, because of concerns about rare and potentially life-threatening blood clots.

Novavax has been described as a more traditional vaccine – a protein subunit shot similar to one people have long received for protection against influenza, pertussis (whooping cough), diphtheria, and tetanus.

“Having a protein-based alternative may be more comfortable for some in terms of their acceptance of vaccines,” Dr. Marks said. “We do have a problem with vaccine uptake that is very serious in the United States. And anything we can do to get people more comfortable to be able to accept these potentially life-saving medical products is something that we feel we are compelled to do.”

Dr. Marks offered these remarks in answer to an FDA panelist’s question about the need to consider an EUA for yet another vaccine.

EUAs are special clearances the FDA can grant in connection with public health emergencies such as the pandemic. The FDA used EUAs for the initial December 2020 clearances of the Pfizer-BioNTech and Moderna vaccines. It has since granted normal approvals for both of these mRNA-based vaccines, based on larger bodies of evidence gathered and submitted by their developers.

During the meeting, the FDA panelists in general appeared comfortable with the idea of granting another EUA for a vaccine. There was agreement that the shot appeared to work in key tests, although these were done before the rise of the Omicron variant.

In a key test, known as study 301, the Novavax vaccine was judged to be 90.4% effective. In the study, 17 of the 17,272 people who got the Novavax vaccine developed COVID-19, compared with 79 of the 8,385 in the placebo group.

Panelists expressed disappointment with the lack of information about how the shot would work now.

“We’re looking at the efficacy against strains that don’t exist any longer,” said panelist Eric J. Rubin, MD, PhD, a Harvard professor and editor of the New England Journal of Medicine.

Still, Dr. Rubin added that he agreed with the argument the FDA’s Dr. Marks had made earlier for an EUA for the Novavax vaccine.

“If there really is a population of patients who are willing to take this and not willing to take the existing vaccines, I think it’s pretty compelling,” Dr. Rubin said.

Other FDA panelists were skeptical of this argument. Jay Portnoy, MD, who was listed on the FDA roster as the panel’s consumer representative, said he has close friends who are vaccine skeptics.

“Their hesitancy is more ideological than technological,” said Dr. Portnoy of Children’s Mercy Hospital, Kansas City, Mo. “So I really doubt that this vaccine is going to crack that nut, but perhaps some individuals would get this when they wouldn’t get the other ones.”
 

Myocarditis, pericarditis

The Novavax vaccine is already authorized in other countries, including Canada. Novavax in February announced that it had begun shipping its first doses of the vaccine to European Union member states. The vaccine can be moved through existing vaccine supply and cold chain channels instead of requiring complex new delivery procedures.

That could prove an advantage in time, said FDA panelist Michael Nelson, MD, PhD, of the University of Virginia, Charlottesville.

“Who knows even with supply chain challenges down the road, it will be nice to have options going forward,” Dr. Nelson said. 

As with other COVID-19 vaccines, clinicians and researchers are still working to understand the potential risk for inflammation of heart muscle and nearby tissue with vaccination. Most patients with myocarditis or pericarditis who sought medical care for these conditions responded well to medicine and rest and felt better quickly, the CDC says on its website. They usually return to their normal daily activities after their symptoms improve.

At the June 7 meeting, Dr. Nelson said there may be cases of myocarditis that go undetected.

“Our signals are those who get admitted to the emergency room and the hospital,” he said. “I’m quite convinced that there are others who are experiencing cardiac events of lesser severity that are worthy of being studied, both from mechanistic and outcomes standpoints. So we have a lot of work to do.”

In looking at results for an initial pool of 40,000 people who received the Novavax vaccine, there were five reported cases of myocarditis or pericarditis developing within 20 days of people getting the shot, the FDA staff said in its presentation on safety.

In a briefing document released ahead of the advisory committee meeting, the FDA staff flagged this number of cases in a relatively small database as a concern, noting it “could be higher than reported during postauthorization use of mRNA COVID-19 vaccines (for which no cases were identified in preauthorization evaluation).”

Novavax officials took a somewhat unusual step of responding in public. The Gaithersburg, Md.–based company on June 3 issued a statement saying researchers had come to “expect to see natural background events of myocarditis in any sufficiently large database, and that young males are at higher risk.”

The data from the company’s placebo-controlled studies show that, overall, in its clinical development program, the rate of myocarditis was balanced between the vaccine and placebo arms (0.007% and 0.005%), Novavax said.

At the June 7 meeting, FDA panelists including Dr. Nelson, and Paul A. Offit, MD, of Children’s Hospital of Philadelphia, urged continued study to try to determine whether and how the vaccines could trigger myocarditis. Investments made now in pursuing these questions related to COVID-19 shots may pay off later, Dr. Offit said.

“We can use that knowledge to make safer vaccines for a disease that is going to be with us for decades, if not longer,” he said.

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

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

The first decline in COVID-19 cases among children since early April may have been holiday related, but the shortened week also brought news about vaccination for the youngest children.

The Food and Drug Administration has accepted Pfizer’s application for a COVID-19 vaccine for children under age 5, so vaccination could begin as early as June 21, according to White House COVID-19 response coordinator Ashish Jha, MD.

“We know that many, many parents are eager to vaccinate their youngest kids and it’s important to do this right,” Dr. Jha said at a White House press briefing June 2. “We expect that vaccinations will begin in earnest as early as June 21 and really roll on throughout that week.”

Decline may just be underreporting

Over on the incidence side of the pandemic, the total number of cases reported for the week of May 27 to June 2 was about 87,000, a drop of 22% from May 20-26 and the first decline after 7 straight weeks of increases. “Testing and reporting may have been affected by the holiday weekend [since] states may change their reporting schedules, which may cause irregularities in trends,” the American Academy of Pediatrics and the Children’s Hospital association said in their latest COVID report.

The decline in new cases was not spread uniformly across the four major regions of the United States. The count actually went up in the West for the week of May 27 to June 2, while the South saw the largest decline. The Midwest and Northeast, meanwhile, saw new cases drop for the second straight week, the AAP and CHA said.

The cumulative number of COVID-19 cases in children was up to 13.45 million as of June 2, with children representing 18.9% of all cases since the start of the pandemic, according to the two organizations. The Centers for Disease Control and Prevention reported figures of 13.14 million and 17.5% on June 6.

The AAP/CHA estimates, however, are based on state data that have become increasingly hard to obtain and subject to inconsistency. “Shortages of COVID-19 tests during surges and the increasing use of COVID-19 home tests likely affect the undercounting of COVID-19 cases,” they noted, and “at times when COVID-19 transmission is low, states might reduce the frequency information is updated.”
 

Vaccinations held steady over the holiday

The ongoing vaccination effort in children aged 5 years and older did not show a Memorial Day drop-off, as initial vaccinations held at 43,000 in 5- to 11-year-olds and at 27,000 in 12- to 17-year-olds for a second consecutive week. That number has ranged from 34,000 to 70,000 for the younger children and from 25,000 to 47,000 for the older group since mid-March, the AAP said in a separate weekly report.

Despite weekly vaccine initiations that have been roughly double those of the older children for months, the 5- to 11-year-olds are still only at 36.0% coverage with at least one dose, compared with 69.5% for the 12- to-17-year-olds. Full vaccination for the two age groups comes in at 29.3% and 59.6%, respectively, as of June 6, according to the CDC’s COVID Data Tracker.
 

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

COPENHAGEN – Most patients with immune-mediated inflammatory diseases (IMID) should not be considered at high risk for severe COVID-19 breakthrough infections, but those on anti-CD20 therapy are the exception, data from a large prospective, cohort study show.

“Overall, the data are reassuring, with conventional risk factors, such as age, and comorbidities seeming to be more important regarding risk of severe COVID-19 breakthrough infections than rheumatic disease or immunosuppressant medication,” said Laura Boekel, MD, from Amsterdam UMC, who presented the study at the annual European Congress of Rheumatology.

peterschreiber_media/iStock/Getty Images

But, she added, there was an exception for anti-CD20 therapy. “This is especially relevant for patients with conventional risk factors that might accumulate, and rheumatologists might want to consider alternative treatment options if possible. It is important to inform patients about the risks of anti-CD20.”

Another study, presented during the same session at the congress by Rebecca Hasseli, MD, from the University of Giessen (Germany) saw no deaths and no COVID-19 related complications in a cohort of triple-vaccinated patients with inflammatory rheumatic diseases, despite a higher median age and a higher rate of comorbidities compared to double-vaccinated and unvaccinated cohorts.

Ingrid Jyssum, MD, from Diakonhjemmet Hospital, Oslo, who presented results of the Nor-vaC study investigating the impact of different DMARDs on the immunogenicity of a third COVID-19 vaccine dose, welcomed the research by Dr. Boekel and Dr. Hasseli.

“The findings of Hasseli are interesting in the light of our data on serological response after the third dose, with a lack of breakthrough infections after three doses corresponding well to the robust antibody response that we found in our cohort,” she remarked. “This is very reassuring for our patients. Our own work together with the findings of Hasseli and Boekel demonstrate that additional vaccine doses are important to keep this population well protected against severe COVID-19 infections.”

The Nor-vaC study was conducted with a cohort of 1,100 patients with inflammatory joint and bowel diseases. “These patients had attenuated antibody responses after two vaccine doses; however, we found that a third vaccine dose brought the humoral response in patients up to the antibody levels that healthy controls had after two doses,” said Dr. Jyssum. “In addition, we found that the decline in antibodies after the third dose was less than the decline seen after the second dose. Importantly, the third dose was safe in our patients, with no new safety issues.”
 

Breakthrough infections and immunosuppressants

“Like the rest of the world, we were wondering if our patients were at increased risk of COVID-19, and if the immunosuppressants used by these patients influenced their risk,” said Dr. Boekel.

The researchers compared both the incidence and severity of COVID-19 breakthrough infections with the SARS-CoV-2 Delta variant in a population of fully vaccinated IMID patients taking immunosuppressants and controls (IMID patients not taking immunosuppressants and healthy controls).

Two large ongoing, prospective, multicenter cohort studies provided pooled data collected between February and December 2021 using digital questionnaires, standardized electronic case record forms, and medical files.

Finger-prick tests were used to collect blood samples that were analyzed after vaccination against SARS-CoV-2 for anti–receptor-binding domain (RBD) antibodies, and antinucleocapsid antibodies to identify asymptomatic breakthrough infections. Any associations between antibodies and the incidence of breakthrough infections were generated, and results were adjusted for sex, cardiovascular disease, chronic pulmonary disease, obesity, and vaccine type.

The analysis included 3,207 IMID patients taking immunosuppressants, and 1,810 controls (985 IMID patients not on immunosuppressants and 825 healthy controls).

Initially, Dr. Boekel and her colleagues looked at incidence of infections and hospitalizations prior to vaccination, and then after vaccination, which was the main aim of the study.

Prior to vaccination, hospitalization risk for COVID-19 was somewhat higher for IMID patients overall compared with controls, reported Dr. Boekel. “But those treated with anti-CD20 therapy, demonstrated much greater risk for severe disease.”

After the SARS-CoV-2 vaccination campaign began, the researchers then looked at how immunosuppressants influenced humoral response to SARS-CoV-2 vaccination.

“Anti-CD20 therapy showed the greatest impact on humoral immune response after SARS-CoV-2 vaccination,” said Dr. Boekel. Other immunosuppressant drugs had variable effects on humoral and cellular immunity. 

Once they had established that immunosuppressant drugs impaired immune responses to SARS-CoV-2 vaccination, the researchers wanted to determine if this affected clinical outcomes. Blood samples taken 28 days after the second vaccination enabled Dr. Boekel and her colleagues to see if antibody production was associated with breakthrough infections.   

Breakthrough infections were seen in 5% of patients on immunosuppressants, 5% of patients not on immunosuppressants, and 4% of healthy controls. Also, asymptomatic COVID-19 breakthrough cases were comparable between IMID patients taking immunosuppressants and controls, at 10% in each group.

“We saw that the incidence [of getting COVID-19] was comparable between groups, independent of whether they were receiving immunosuppressants or not, or healthy controls. However, if they developed antibodies against the two vaccinations the chance of getting infected was lower,” reported Dr. Boekel.

Hospitalization (severe disease) rates were also comparable between groups. “Patients with rheumatic diseases, even when treated with immunosuppressants were not at increased risk of severe disease from Delta breakthrough infections,” added the researcher. “Cases that were hospitalized were mainly elderly and those with comorbidities, for example cardiovascular disease and cardiopulmonary disease.”

Hospital admissions were 5.4% in patients on immunosuppressants, 5.7% in those not on immunosuppressants, and 6% in health controls.

However, once again, there was one exception, Dr. Boekel stressed. “Patients treated with anti-CD20 therapy were at increased risk of severe disease and hospitalization.”

Omicron variant has a different transmissibility than Delta, so the researchers continued the study looking at the Omicron variant. The data “were mostly reassuring,” said Dr. Boekel. “As expected, hospitalization rates decreased overall, with the exception of patients on anti-CD20 therapy where, despite overall reduced pathogenicity, patients remain at increased risk.”

She said that they were awaiting long-term data so the data reflect only short-term immunity against Omicron. “However, we included many elderly and patients with comorbidities, so this made the analysis very sensitive to detect severe cases,” she added.

Breakthrough infection among double- and triple-vaccinated patients

A lower rate of COVID-19 related complications and deaths were seen in patients who were triple-vaccinated against SARS-CoV-2, than in double-vaccinated or unvaccinated patients, despite the former having more comorbidities and use of rituximab (Rituxan), said Dr. Hasseli.

“These data support the recommendation of booster vaccination to reduce COVID-19-related mortality in patients with inflammatory rheumatic diseases [IRDs],” she said.

“A small number of COVID-19 cases were seen in patients with IRD after vaccinations, and in a few cases, hospitalizations were required. Breakthrough infections were mostly seen in patients on B-cell depletion therapy,” she added.

Dr. Hasseli and her colleagues looked at the characteristics and outcomes of SARS-CoV-2 breakthrough infections among double- and triple-vaccinated patients with IRD.

“We wanted to understand if patients with IRD are protected in the same way as the general population following vaccination, given that these patients receive drugs that might impair the immune response,” she explained.

Data for analysis were drawn from the German COVID-19-IRD registry covering February 2021 and January 2022, and patients who were double- or triple- vaccinated against COVID-19 either 14 days or more prior to a SARS-CoV-2 infection were included. Type of IRD, vaccine, immunomodulation, comorbidities, and outcome of the infection were compared with 737 unvaccinated IRD patients with COVID-19. Those with prior COVID-19 were excluded.

Cases were stratified by vaccinations status: unvaccinated (1,388 patients, median age 57 years); double vaccinated (462, 56 years) and triple vaccinated (301, 53 years). Body mass index was similar across groups (25-26 kg/m²), and time between SARS-CoV-2 infection and last vaccination was 156 days in double-vaccinated patients, and 62 days in triple-vaccinated patients.

Patients had rheumatoid arthritis in 44.7% and 44.4% of unvaccinated and double-vaccinated patients respectively, but fewer triple-vaccinated patients had RA (37.2%). Triple vaccination was seen in 32.2% of patients with spondyloarthritis, 16.6% connective tissue diseases, 5.3% other vasculitis, and 3.3% ANCA-associated vasculitis. Of triple-vaccinated patients, 26.2% were treated with tumor necrosis factor-alpha (TNF-alpha) inhibitors, and 6.3% with rituximab, while 5.3% were not on immunomodulation. At least 25% were treated with glucocorticoids, reported Dr. Hasseli.

“Arterial hypertension and diabetes, that might be risk factors for COVID-19, were less frequently reported in triple-vaccinated patients. More patients in the double-vaccinated group [42.9%] than the triple-vaccinated [23.8%] reported absence of relevant comorbidities,” she said.

COVID-19 related complications were less often reported in double- and triple-vaccinated groups with hospitalizations at 9.5% and 4.3% in double and triple-vaccinated people respectively.

Dr. Boekel and Dr. Hasseli report no relevant conflicts of interest.

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

Among an estimated 87% of people with HIV (PWH) whose condition has been diagnosed, roughly 66% have received medication. But only half are retained in care, leaving substantial risk for viral rebound and further HIV transmission.

A variety of factors contribute to falling out of care (OOC), a primary reason why a team from the Centers for Disease Control and Prevention reviewed over three decades of studies with the goal of identifying best practices for re-engagement.

The research, which was published  in the journal AIDS, underscores the need for more customized strategies, rather than a one-size-fits-all approach, especially for historically underserved communities.

“Many study participants across the studies included in this review represented communities who have the largest challenges with remaining in care,” Darrel H. Higa, PhD, MSW, lead study author and a behavioral scientist at the CDC in Atlanta, told this news organization.

For example, “Some face barriers that may limit their access to care ... including not having health insurance or being unable to pay for doctor visits or medication, HIV-related stigma, racism, homophobia, transphobia, health literacy, and a lack of providers who specialize in HIV care,” he said.

Other challenges relate to personal barriers, such as competing priorities (for example, work or childcare), substance use, mental health disorders, transportation problems, or a lack of social support.

Even with improvements that address some of these barriers, such as expanded access to health care insurance and broader provision of medical care and HIV medications through the national Ryan White program, structural challenges and social barriers persist.
 

Better versus best practices

In their analysis, the CDC team expanded the scope of prior reviews by including literature published between 2000 and 2020 and further conducted meta-analyses to assess the effectiveness of five common, non mutually exclusive interventions:

• patient navigation
• appointment help/alerts
• psychosocial support
• transportation/appointment reminders
• data-to-care HIV care outcomes (using health department surveillance data and/or patient health records to identify and re-engage OOC PWH)

The majority of the 26,154 participants in 39 included studies (incorporating 42 unique interventions) were male (71%) and Black (64%); the most common time frame for OOC was between 6 and 12 months, but some studies used a time frame of 3-4 months, and others more than 12 months.

Definitions for re-engagement and retention were likewise inconsistent across studies but most commonly involved having an HIV medical visit or viral load test record between 2 and 6 months (re-engagement), and ≥ 1 medical visits in each 6-month period a minimum of 60 days apart for a period of over 2 years (retention).

This is notable, as it points to the role played – at least in part – by the care fragmentation inherent in the United States health care system. Without national indicators or thresholds for clinical outcomes, services are unlikely to reach scale.

“You can’t expect retention in care until you have a close to seamless, less fragmented safety net in the United States,” said Mary Jane Rotheram-Borus, PhD, distinguished professor of clinical psychology and director of the Global Center for Children and Families at the Semel Institute for Neuroscience and Human Behavior at the University of California, Los Angeles. (Dr. Rotheram-Borus authored an accompanying editorial but was not involved in the study.)

Nevertheless, review findings highlighted that overall, the five interventions appeared to improve care re-engagement (odds ratio = 1.79, 95% confidence interval, 1.36-2.36), care retention (OR = 2.01; 95% CI, 1.64-2.46), and viral suppression (OR = 2.50; 95% CI, 1.87-2.24).

Overall, the five strategies were associated with optimal re-engagement and retention in care. In addition, four of them were associated with viral suppression for PWH who were OOC during the study time frame. The one exception was data-to-care, for which the evidence supporting an association with viral suppression was unclear.

Because of the similarities between patient navigation and transportation/appointment accompaniment, the researchers also compared PWH who received combined strategies to those who did not.

“The findings suggest that patient navigation services that often include helping with transportation to appointments or accompanying PWH to appointments may be more effective compared to interventions without the combination,” explained Dr. Higa, “especially for communities with the largest challenges remaining in care.”

He added that, moving forward, many of the same strategies that help re-engage out-of-care PWH may be useful for retention. These include co-locating services, outreach, mental health services, clinical care models, telemedicine, and financial incentives.

Despite its financial investments toward ending the HIV epidemic, the United States arguably still has a long way to go to improve retention and care.

Still, Dr. Rotheram-Borus underscores the silver lining.

“The breakthroughs in medication are substantial,” she said, pointing to her own research, which has shown that at least 60% of newly infected, poor, LGBTQ+ young people up to age 24 have been linked to care and are adherent enough to be virally suppressed.

For PWH who are out of care, perhaps treatment advances – including long-acting injectables – may ultimately fill in the gaps.

Dr. Higa and Dr. Rotherum-Borus report no relevant financial relationships.

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

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

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

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

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

With monkeypox now circulating in the United States, expecting mothers may worry about what might happen if they contract the infection while pregnant.

As of today, 25 cases of monkeypox have been confirmed in the United States since the outbreak began in early May, according to the U.S. Centers for Disease Control and Prevention. Although none of those cases has involved a pregnant person, the World Health Organization says monkeypox can pass from mother to fetus before delivery or to newborns by close contact during and after birth.

The case count could grow as the agency continues to investigate potential infections of the virus. In a conference call Friday, health officials stressed the importance of contact tracing, testing, and vaccine treatment.

As physicians in the United States are scrambling for information on ways to treat patients, a new study, published in Ultrasound in Obstetrics & Gynecology, could help clinicians better care for pregnant people infected with monkeypox. The authors advise consistently monitoring the fetus for infection and conducting regular ultrasounds, among other precautions. 

Asma Khalil, MBBCh, MD, a professor of obstetrics and fetal medicine at St. George’s University, London, and lead author of the new study, said the monkeypox outbreak outside Africa caught many clinicians by surprise.

“We quickly realized very few physicians caring for pregnant women knew anything at all about monkeypox and how it affects pregnancy,” Dr. Khalil told this news organization. “Clinicians caring for pregnant women are likely to be faced soon with pregnant women concerned they may have the infection – because they have a rash, for example – or indeed pregnant women who do have the infection.”

According to the CDC, monkeypox can be transmitted through direct contact with the rash, sores, or scabs caused by the virus, as well as contact with clothing, bedding, towels, or other surfaces used by an infected person. Respiratory droplets and oral fluids from a person with monkeypox have also been linked to spread of the virus, as has sexual activity.

Although the condition is rarely fatal, infants and young children are at the greatest risk of developing severe symptoms, health officials said. 

The U.S. Food and Drug Administration has approved a monkeypox vaccine, Jynneos (Bavarian Nordic A/S), for general use, but it has not been specifically approved for pregnant people. However, a study of 300 pregnant women who received the vaccine reported no adverse reactions or failed pregnancies linked to the shots.

The new review suggests that women who have a confirmed infection during pregnancy should have a doctor closely monitor the fetus until birth.

If the fetus is over 26 weeks or if the mother is unwell, the fetus should be cared for with heart monitoring, either by a doctor or remotely every 2-3 days. Ultrasounds should be performed regularly to confirm that the fetus is still growing well and that the placenta is functioning properly.

Further into the pregnancy, monitoring should include measurements of the fetus and detailed assessment of the fetal organs and the amniotic fluid. Once the infection is resolved, the risk to the fetus is small, according to Dr. Khalil. However, since data are limited, she recommended an ultrasound scan every 2-4 weeks. At birth, for the protection of the infant and the mother, the baby should be isolated until infection is no longer a risk.

The Royal College of Obstetricians & Gynaecologists is preparing guidance on the management of monkeypox in pregnant people, Dr. Khalil said. The American College of Obstetricians and Gynecologists said it is “relying on the CDC for the time being,” according to a spokesperson for ACOG. 

“There is a clear need for further research in this area,” Dr. Khalil said. “The current outbreak is an ideal opportunity to make this happen.”

Dr. Khalil has disclosed no relevant financial relationships.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

Patients with multiple sclerosis (MS) treated with the B-cell-depleting medication rituximab who have not yet been vaccinated against COVID-19 should get the initial vaccination as soon as possible but wait to get a booster shot until B-cell levels increase, new research suggests.

In a prospective cohort study, 90% of patients taking rituximab whose B-cell level was at least 40 cells/mcL had a sufficient antibody response to the Pfizer vaccine, whereas among those with lower levels, the antibody response was significantly lower.

Results also showed a wide variation in the length of time needed for adequate B-cell restoration. Some patients needed a year or longer for levels to become adequate.

The findings led the hospital where the study was conducted to suspend rituximab therapy until patients could be vaccinated. The findings also prompted researchers to call for new guidelines on vaccine scheduling that are based on B-cell levels and not on the current criteria of length of time since last treatment.

“It’s meaningless to just go by some recommendation covering time since the last treatment,” study investigator Joachim Burman, MD, PhD, a consultant neurologist at Uppsala University Hospital and an associate professor at Uppsala University, both in Sweden, told this news organization.

“It’s misleading and potentially harmful for patients,” Dr. Burman said.

The findings were published online  in JAMA Network Open.
 

Finding the cutoff

Drugs such as rituximab target CD20, a protein found on the surface of B cells, resulting in B-cell depletion.

Rituximab is the most common MS therapy used in Sweden. The drug is approved in the United States to treat rheumatoid arthritis and some forms of cancer, but it is not approved for treatment of MS.

Prior research showed that antibody response to COVID-19 vaccines was lower in patients receiving B-cell therapy than in the general population. That was not altogether surprising, given the fact that studies have found a similarly weakened antibody response to other vaccines.

But before now, there was no known B-cell threshold sufficient to mount an acceptable antibody response following COVID vaccination.

Researchers enrolled 67 patients in the study. Of those patients, 60 had received rituximab treatment, and seven had not.

Approximately 6 months after the last rituximab dose, the B-cell count was lower than 10/mcL for 40% of patients. In that group, rituximab treatment duration was the only factor significantly associated with slower B-cell mobilization (median duration, 4.0 years, vs. 2.1; P = .002).
 

Close monitoring needed

Six weeks after vaccination with tozinameran, the mRNA vaccine manufactured by Pfizer, 28% of patients failed to generate a sufficient antibody response. Among those patients, the median B-cell count was 22/mcL, versus 51/mcL for the remainder of the cohort (P < .001).

A cutoff value of 40/mcL rendered adequate levels of anti-spike immunoglobulin G antibodies in 90% of patients and a strong response in anti-RBD antibodies in 72%.

Study participants did register an adequate T-cell response to the vaccine, suggesting at least some level of protection.

Because MS patients are at increased risk for serious illness from SARS-CoV-2 infection, the investigators recommend that patients with MS receive their initial COVID vaccines as soon as possible – but that they should hold off on receiving a booster until their B-cell counts reach 40/mcL.

Regarding when a clinician should re-vaccinate, “the results from our study strongly suggest that you should not do that right away or just follow some generic guideline,” Dr. Burman said.

“You should closely monitor the B-cell values, and re-vaccinate once those B- cells hit the level of 40 cells/mcL” he added.

Dr. Burman said he would expect that their findings would hold with the other mRNA vaccine and with any other B-cell therapy.
 

Too soon for B-cell measures?

Commenting for this news organization, Robert J. Fox, MD, staff neurologist at the Mellen Center for MS and vice-chair for research at the Neurological Institute at Cleveland Clinic, Ohio, said the B-cell threshold identified in the study is much higher than what is typically seen in patients who undergo treatment with ocrelizumab, an anti-CD20 B-cell therapy approved in the United States for treating MS.

“Decisions about treatment interval need to balance efficacy in treating MS with safety, including response to vaccines,” said Dr. Fox, who was not involved with the research.

“Given the unknown efficacy of these extended intervals, I don’t think we’re at the point of making management recommendations based upon B-cell counts,” he added.

And yet, Uppsala University Hospital, where the study was conducted, and other centers in Sweden decided to do just that. They suspended administering rituximab to patients with MS until the patients were vaccinated. For patients newly diagnosed with MS, therapy was initiated using another disease-modifying treatment, and for those who were due for a rituximab infusion, that treatment was delayed.

Only one patient experienced a mild MS relapse during the rituximab suspension, and that case went into remission within a week, Dr. Burman reported.

“Ever since the Bar-Or report showing that the humeral response to vaccines is markedly diminished in MS patients treated with anti-CD20 therapies, clinicians have been struggling to balance those safety concerns related to anti-CD20 monoclonal antibody treatments and the clinical benefit of this treatment class,” Dr. Fox said.

“Given the uncharted waters of the COVID pandemic, clinicians made judgments and decisions as best they could, given the paucity of data,” he noted.

“At this point, we don’t know which decisions were right or wrong, but I certainly don’t think we should judge clinicians for making decisions the best they could.”

The study was funded by the Engkvist Foundation, the Marianne and Marcus Wallenberg Foundation, and the Swedish Society for Medical Research. Dr. Burman reported no relevant financial relationships. Dr. Fox has received consulting fees from Genentech/Roche, Biogen, and other companies that promote MS therapies.

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

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.

In a new risk-assessment document, the European Centre for Disease Prevention and Control summarizes what we currently know about monkeypox and recommends that European countries focus on the identification and management of the disease as well as contract tracing and prompt reporting of new cases of the virus.

Recent developments

From May 15 to May 23, in eight European Union member states (Belgium, France, Germany, Italy, the Netherlands, Portugal, Spain, and Sweden) a total of 85 cases of monkeypox were reported; they were acquired through autochthonous transmission. Current diagnosed cases of monkeypox have mainly been recorded in men who have sexual relations with other men, suggesting that transmission may occur during sexual intercourse, through infectious material coming into contact with mucosa or damaged skin, or via large respiratory droplets during prolonged face-to-face contact.

Andrea Ammon, MD, director of the ECDC, stated that “most current cases have presented with mild symptoms of the disease, and for the general population, the chance of diffusion is very low. However, the likelihood of a further spread of the virus through close contact, for example during sexual activities among people with multiple sexual partners, is considerably increased.”

Stella Kyriakides, European commissioner for health and food safety, added, “I am worried about the increase of cases of monkeypox in the EU and worldwide. We are currently monitoring the situation and, although, at the moment, the probability of it spreading to the general population is low, the situation is evolving. We should all remain alert, making sure that contact tracing and a sufficient diagnostic capacity are in place and guarantee that vaccines and antiviral drugs are available, as well as sufficient personal protective equipment [PPE] for health care professionals.”
 

Routes of transmission

Monkeypox is not easily spread among people. Person-to-person transmission occurs through close contact with infectious material, coming from skin lesions of an infected person, through air droplets in the case of prolonged face-to-face contact, and through fomites. So far, diagnosed cases suggest that transmission can occur through sexual intercourse.

The incubation period is 5-21 days, and patients are symptomatic for 2-4 weeks.

According to the ECDC, the likelihood of this infection spreading is increased among people who have more than one sexual partner. Although most current cases present with mild symptoms, monkeypox can cause severe disease in some groups (such as young children, pregnant women, and immunosuppressed people). However, the probability of severe disease cannot yet be estimated precisely.

The overall risk is considered moderate for people who have multiple sexual partners and low for the general population.
 

Clinical course

The disease initially presents with fever, myalgia, fatigue, and headache. Within 3 days of the onset of the prodromal symptoms, a centrifugal maculopapular rash appears on the site of primary infection and rapidly spreads to other parts of the body. The palms of the hands and bottoms of the feet are involved in cases where the rash has spread, which is a characteristic of the disease. Usually within 12 days, the lesions progress, simultaneously changing from macules to papules, blisters, pustules, and scabs before falling off. The lesions may have a central depression and be extremely itchy.

If the patient scratches them, a secondary bacterial infection may take hold (for which treatment with oral antihistamines is indicated). Lesions may also be present in the oral or ocular mucous membrane. Either before or at the same time as onset of the rash, patients may experience swelling of the lymph nodes, which usually is not seen with smallpox or chickenpox.

The onset of the rash is considered the start of the infectious period; however, people with prodromal symptoms may also transmit the virus.

Most cases in people present with mild or moderate symptoms. Complications seen in endemic countries include encephalitis, secondary bacterial skin infections, dehydration, conjunctivitis, keratitis, and pneumonia. The death rate ranges from 0% to 11% in endemic areas, with fatalities from the disease mostly occurring in younger children.

There is not a lot of information available on the disease in immunosuppressed individuals. In the 2017 Nigerian epidemic, patients with a concomitant HIV infection presented with more severe disease, with a greater number of skin lesions and genital ulcers, compared with HIV-negative individuals. No deaths were reported among seropositive patients. The main sequelae from the disease are usually disfiguring scars and permanent corneal lesions.
 

Treatment

No smallpox vaccines are authorized for use against monkeypox, however the third-generation smallpox vaccine Imvanex (Modified Vaccinia Ankara) has been authorized by the European Medicines Agency (EMA) for the EU market against smallpox and has demonstrated to provide protection in primates.

Old-generation smallpox vaccines have significant side effects, are no longer authorized, and should no longer be used. It is also important to note the lack of safety data for the use of Imvanex in immunocompromised people.

For this reason, National Immunization Technical Advisory Groups have been asked to develop specific guidelines for vaccination in close contacts of patients with monkeypox. The use of a smallpox vaccine for preexposure prophylaxis cannot be considered now, when taking into account the risk-benefit ratio.

In regard to treatment, tecovirimat is the only antiviral drug with an EMA-authorized indication for orthopoxvirus infection.

Brincidofovir is not authorized in the EU but has been authorized by the US Food and Drug Administration. However, availability on the European market is limited somewhat by the number of doses.

According to the ECDC, health care authorities should provide information about which groups should have priority access to treatment.

The use of antivirals for postexposure prophylaxis should be investigated further. Cidofovir is active in vitro for smallpox but has a pronounced nephrotoxicity profile that makes it unsuitable for first-line treatment.

The ECDC document also proposes an interim case definition for epidemiologic reporting. Further indications will also be provided for the management of monkeypox cases and close contacts. Those infected should remain in isolation until the scabs have fallen off and should, above all, avoid close contact with at-risk or immunosuppressed people as well as pets.

Most infected people can remain at home with supportive care.
 

Prevention

Close contacts for cases of monkeypox should monitor the development of their symptoms until 21 days have passed from their most recent exposure to the virus.

Health care workers should wear appropriate PPE (gloves, water-resistant gowns, FFP2 masks) during screening for suspected cases or when working with confirmed cases. Laboratory staff should also take precautions to avoid exposure in the workplace.

Close contacts of an infected person should not donate blood, organs, or bone marrow for at least 21 days from the last day of exposure.

Finally, the ECDC recommends increasing proactive communication of the risks to increase awareness and provide updates and indications to individuals who are at a greater risk, as well as to the general public. These messages should highlight that monkeypox is spread through close person-to-person contact, especially within the family unit, and also potentially through sexual intercourse. A balance, however, should be maintained between informing the individuals who are at greater risk and communicating that the virus is not easily spread and that the risk for the general population is low.
 

Human-to-animal transmission

A potential risk for human-to-animal transmission exists in Europe; therefore, a close collaboration is required between human and veterinary health care authorities, working together to manage domestic animals exposed to the virus and to prevent transmission of the disease to wildlife. To date, the European Food Safety Authority is not aware of any reports of animal infections (domestic or wild) within the EU.

There are still many unknown factors about this outbreak. The ECDC continues to closely monitor any developments and will update the risk assessment as soon as new data and information become available.

If human-to-animal transmission occurs and the virus spreads among animal populations, there is a risk that the disease could become an endemic in Europe. Therefore, human and veterinary health care authorities should work together closely to manage cases of domestic animals exposed to the virus and prevent transmission of the disease to wildlife.

A version of this article appeared on Medscape.com. This article was translated from Univadis Italy.