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In Case You Missed It: COVID
Patient health suffers amid pandemic health care shortages
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
What the Biden-Harris COVID-19 Advisory Board is missing
On Nov. 9, the Biden-Harris administration announced the members of its COVID-19 Advisory Board. Among them were many esteemed infectious disease and public health experts – encouraging, given that, for now, the COVID-19 pandemic shows no signs of slowing down. Not among them was a mental health professional.
As psychiatrists, we did not find this omission surprising, given the sidelined role our specialty too often plays among medical professionals. But we did find it disappointing. Not having a single behavioral health provider on the advisory board will prove to be a mistake that could affect millions of Americans.
Studies continue to roll in showing that patients with COVID-19 can present during and after infection with neuropsychiatric symptoms, including delirium, psychosis, and anxiety. In July, a meta-analysis published in The Lancet regarding the neuropsychological outcomes of earlier diseases caused by coronaviruses – severe acute respiratory syndrome and Middle East respiratory syndrome – suggested that, in the short term, close to one-quarter of patients experienced confusion representative of delirium. In the long term, following recovery, respondents frequently reported emotional lability, impaired concentration, and traumatic memories. Additionally, more recent research published in The Lancet suggests that rates of psychiatric disorders, dementia, and insomnia are significantly higher among survivors of COVID-19. This study echoes the findings of an article in JAMA from September that reported that, among patients who were hospitalized for COVID-19, mortality rates were higher for those who had previously been diagnosed with a psychiatric condition. And overall, the pandemic has been associated with significantly increased rates of anxiety and depression symptoms.
Although this research is preliminary,
This is especially true when you consider the following:
- It is very difficult to diagnose and treat mental health symptoms in a primary care setting that is already overburdened. Doing so results in delayed treatment and increased costs.
- In the long term, COVID-19 survivors will overburden the already underfunded mental healthcare system.
- Additional unforeseen psychological outcomes stem from the myriad traumas of events in 2020 (eg, racial unrest, children out of school, loss of jobs, the recent election).
Psychiatric disorders are notoriously difficult to diagnose and treat in the outpatient primary care setting, which is why mental health professionals will need to be a more integral part of the postpandemic treatment model and should be represented on the advisory board. Each year in the United States, there are more than 8 million doctors’ visits for depression, and more than half of these are in the primary care setting. Yet fewer than half of those patients leave with a diagnosis of depression or are treated for it.
Historically, screening for depression in the primary care setting is difficult given its broad presentation of symptoms, which include nonspecific physical complaints, such as digestive problems, headaches, insomnia, or general aches and pains. These shortcomings exist despite multiple changes in guidelines, such as regarding the use of self-screening tools and general screening for specific populations, such as postpartum women.
But screening alone has not been an effective strategy, especially when certain groups are less likely to be screened. These include older adults, Black persons, and men, all of whom are at higher risk for mortality after COVID-19. There is a failure to consistently apply standards of universal screening across all patient groups, and even if it occurs, there is a failure to establish reliable treatment and follow-up regimens. As clinicians, imagine how challenging diagnosis and treatment of more complicated psychiatric syndromes, such as somatoform disorder, will be in the primary care setting after the pandemic.
When almost two-thirds of symptoms in primary care are already “medically unexplained,” how do we expect primary care doctors to differentiate between those presenting with vague coronavirus-related “brain fog,” the run of the mill worrywart, and the 16%-34% with legitimate hypochondriasis of somatoform disorder who won’t improve without the involvement of a mental health provider?
A specialty in short supply
The mental health system we have now is inadequate for those who are currently diagnosed with mental disorders. Before the pandemic, emergency departments were boarding increasing numbers of patients with psychiatric illness because beds on inpatient units were unavailable. Individuals with insurance faced difficulty finding psychiatrists or psychotherapists who took insurance or who were availabile to accept new patients, given the growing shortage of providers in general. Community health centers continued to grapple with decreases in federal and state funding despite public political support for parity. Individuals with substance use faced few options for the outpatient, residential, or pharmacologic treatment that many needed to maintain sobriety.
Since the pandemic, we have seen rates of anxiety, depression, and suicidal thinking increase among adults and youth while many clinics have been forced to lay off employees, reduce services, or close their doors. As psychiatrists, we not only see the lack of treatment options for our patients but are forced to find creative solutions to meet their needs. How are we supposed to adapt (or feel confident) when individuals with or without previous mental illness face downstream consequences after COVID-19 when not one of our own is represented in the advisory board? How can we feel confident that downstream solutions acknowledge and address the intricacy of the behavioral health system that we, as mental health providers, know so intimately?
And what about the cumulative impact of everything else that has happened in 2020 in addition to the pandemic?! Although cataloging the various negative events that have happened this year is beyond the scope of this discussion, such lists have been compiled by the mainstream media and include the Australian brush fires, the crisis in Armenia, racial protests, economic uncertainties, and the run-up to and occurrence of the 2020 presidential election. Research is solid in its assertion that chronic stress can disturb our immune and cardiovascular systems, as well as mental health, leading to depression or anxiety. As a result of the pandemic itself, plus the events of this year, mental health providers are already warning not only of the current trauma underlying our day-to-day lives but also that of years to come.
More importantly, healthcare providers, both those represented by members of the advisory board and those who are not, are not immune to these issues. Before the pandemic, rates of suicide among doctors were already above average compared with other professions. After witnessing death repeatedly, self-isolation, the risk for infection to family, and dealing with the continued resistance to wearing masks, who knows what the eventual psychological toll our medical workforce will be?
Mental health providers have stepped up to the plate to provide care outside of traditional models to meet the needs that patients have now. One survey found that 81% of behavioral health providers began using telehealth for the first time in the past 6 months, owing to the COVID-19 pandemic. If not for the sake of the mental health of the Biden-Harris advisory board members themselves, who as doctors are likely to downplay the impact when struggling with mental health concerns in their own lives, a mental health provider deserves a seat at the table.
Plus, the outcomes speak for themselves when behavioral health providers collaborate with primary care providers to give treatment or when mental health experts are members of health crisis teams. Why wouldn’t the same be true for the Biden-Harris advisory board?
Kali Cyrus, MD, MPH, is an assistant professor of psychiatry and behavioral medicine at the Johns Hopkins School of Medicine, Baltimore, Maryland. She sees patients in private practice and offers consultation services in diversity strategy. Ranna Parekh, MD, MPH, is past deputy medical director and director of diversity and health equity for the American Psychiatric Association. She is currently a consultant psychiatrist at the Massachusetts General Hospital, Boston, and the chief diversity and inclusion officer at the American College of Cardiology.
A version of this article originally appeared on Medscape.com.
On Nov. 9, the Biden-Harris administration announced the members of its COVID-19 Advisory Board. Among them were many esteemed infectious disease and public health experts – encouraging, given that, for now, the COVID-19 pandemic shows no signs of slowing down. Not among them was a mental health professional.
As psychiatrists, we did not find this omission surprising, given the sidelined role our specialty too often plays among medical professionals. But we did find it disappointing. Not having a single behavioral health provider on the advisory board will prove to be a mistake that could affect millions of Americans.
Studies continue to roll in showing that patients with COVID-19 can present during and after infection with neuropsychiatric symptoms, including delirium, psychosis, and anxiety. In July, a meta-analysis published in The Lancet regarding the neuropsychological outcomes of earlier diseases caused by coronaviruses – severe acute respiratory syndrome and Middle East respiratory syndrome – suggested that, in the short term, close to one-quarter of patients experienced confusion representative of delirium. In the long term, following recovery, respondents frequently reported emotional lability, impaired concentration, and traumatic memories. Additionally, more recent research published in The Lancet suggests that rates of psychiatric disorders, dementia, and insomnia are significantly higher among survivors of COVID-19. This study echoes the findings of an article in JAMA from September that reported that, among patients who were hospitalized for COVID-19, mortality rates were higher for those who had previously been diagnosed with a psychiatric condition. And overall, the pandemic has been associated with significantly increased rates of anxiety and depression symptoms.
Although this research is preliminary,
This is especially true when you consider the following:
- It is very difficult to diagnose and treat mental health symptoms in a primary care setting that is already overburdened. Doing so results in delayed treatment and increased costs.
- In the long term, COVID-19 survivors will overburden the already underfunded mental healthcare system.
- Additional unforeseen psychological outcomes stem from the myriad traumas of events in 2020 (eg, racial unrest, children out of school, loss of jobs, the recent election).
Psychiatric disorders are notoriously difficult to diagnose and treat in the outpatient primary care setting, which is why mental health professionals will need to be a more integral part of the postpandemic treatment model and should be represented on the advisory board. Each year in the United States, there are more than 8 million doctors’ visits for depression, and more than half of these are in the primary care setting. Yet fewer than half of those patients leave with a diagnosis of depression or are treated for it.
Historically, screening for depression in the primary care setting is difficult given its broad presentation of symptoms, which include nonspecific physical complaints, such as digestive problems, headaches, insomnia, or general aches and pains. These shortcomings exist despite multiple changes in guidelines, such as regarding the use of self-screening tools and general screening for specific populations, such as postpartum women.
But screening alone has not been an effective strategy, especially when certain groups are less likely to be screened. These include older adults, Black persons, and men, all of whom are at higher risk for mortality after COVID-19. There is a failure to consistently apply standards of universal screening across all patient groups, and even if it occurs, there is a failure to establish reliable treatment and follow-up regimens. As clinicians, imagine how challenging diagnosis and treatment of more complicated psychiatric syndromes, such as somatoform disorder, will be in the primary care setting after the pandemic.
When almost two-thirds of symptoms in primary care are already “medically unexplained,” how do we expect primary care doctors to differentiate between those presenting with vague coronavirus-related “brain fog,” the run of the mill worrywart, and the 16%-34% with legitimate hypochondriasis of somatoform disorder who won’t improve without the involvement of a mental health provider?
A specialty in short supply
The mental health system we have now is inadequate for those who are currently diagnosed with mental disorders. Before the pandemic, emergency departments were boarding increasing numbers of patients with psychiatric illness because beds on inpatient units were unavailable. Individuals with insurance faced difficulty finding psychiatrists or psychotherapists who took insurance or who were availabile to accept new patients, given the growing shortage of providers in general. Community health centers continued to grapple with decreases in federal and state funding despite public political support for parity. Individuals with substance use faced few options for the outpatient, residential, or pharmacologic treatment that many needed to maintain sobriety.
Since the pandemic, we have seen rates of anxiety, depression, and suicidal thinking increase among adults and youth while many clinics have been forced to lay off employees, reduce services, or close their doors. As psychiatrists, we not only see the lack of treatment options for our patients but are forced to find creative solutions to meet their needs. How are we supposed to adapt (or feel confident) when individuals with or without previous mental illness face downstream consequences after COVID-19 when not one of our own is represented in the advisory board? How can we feel confident that downstream solutions acknowledge and address the intricacy of the behavioral health system that we, as mental health providers, know so intimately?
And what about the cumulative impact of everything else that has happened in 2020 in addition to the pandemic?! Although cataloging the various negative events that have happened this year is beyond the scope of this discussion, such lists have been compiled by the mainstream media and include the Australian brush fires, the crisis in Armenia, racial protests, economic uncertainties, and the run-up to and occurrence of the 2020 presidential election. Research is solid in its assertion that chronic stress can disturb our immune and cardiovascular systems, as well as mental health, leading to depression or anxiety. As a result of the pandemic itself, plus the events of this year, mental health providers are already warning not only of the current trauma underlying our day-to-day lives but also that of years to come.
More importantly, healthcare providers, both those represented by members of the advisory board and those who are not, are not immune to these issues. Before the pandemic, rates of suicide among doctors were already above average compared with other professions. After witnessing death repeatedly, self-isolation, the risk for infection to family, and dealing with the continued resistance to wearing masks, who knows what the eventual psychological toll our medical workforce will be?
Mental health providers have stepped up to the plate to provide care outside of traditional models to meet the needs that patients have now. One survey found that 81% of behavioral health providers began using telehealth for the first time in the past 6 months, owing to the COVID-19 pandemic. If not for the sake of the mental health of the Biden-Harris advisory board members themselves, who as doctors are likely to downplay the impact when struggling with mental health concerns in their own lives, a mental health provider deserves a seat at the table.
Plus, the outcomes speak for themselves when behavioral health providers collaborate with primary care providers to give treatment or when mental health experts are members of health crisis teams. Why wouldn’t the same be true for the Biden-Harris advisory board?
Kali Cyrus, MD, MPH, is an assistant professor of psychiatry and behavioral medicine at the Johns Hopkins School of Medicine, Baltimore, Maryland. She sees patients in private practice and offers consultation services in diversity strategy. Ranna Parekh, MD, MPH, is past deputy medical director and director of diversity and health equity for the American Psychiatric Association. She is currently a consultant psychiatrist at the Massachusetts General Hospital, Boston, and the chief diversity and inclusion officer at the American College of Cardiology.
A version of this article originally appeared on Medscape.com.
On Nov. 9, the Biden-Harris administration announced the members of its COVID-19 Advisory Board. Among them were many esteemed infectious disease and public health experts – encouraging, given that, for now, the COVID-19 pandemic shows no signs of slowing down. Not among them was a mental health professional.
As psychiatrists, we did not find this omission surprising, given the sidelined role our specialty too often plays among medical professionals. But we did find it disappointing. Not having a single behavioral health provider on the advisory board will prove to be a mistake that could affect millions of Americans.
Studies continue to roll in showing that patients with COVID-19 can present during and after infection with neuropsychiatric symptoms, including delirium, psychosis, and anxiety. In July, a meta-analysis published in The Lancet regarding the neuropsychological outcomes of earlier diseases caused by coronaviruses – severe acute respiratory syndrome and Middle East respiratory syndrome – suggested that, in the short term, close to one-quarter of patients experienced confusion representative of delirium. In the long term, following recovery, respondents frequently reported emotional lability, impaired concentration, and traumatic memories. Additionally, more recent research published in The Lancet suggests that rates of psychiatric disorders, dementia, and insomnia are significantly higher among survivors of COVID-19. This study echoes the findings of an article in JAMA from September that reported that, among patients who were hospitalized for COVID-19, mortality rates were higher for those who had previously been diagnosed with a psychiatric condition. And overall, the pandemic has been associated with significantly increased rates of anxiety and depression symptoms.
Although this research is preliminary,
This is especially true when you consider the following:
- It is very difficult to diagnose and treat mental health symptoms in a primary care setting that is already overburdened. Doing so results in delayed treatment and increased costs.
- In the long term, COVID-19 survivors will overburden the already underfunded mental healthcare system.
- Additional unforeseen psychological outcomes stem from the myriad traumas of events in 2020 (eg, racial unrest, children out of school, loss of jobs, the recent election).
Psychiatric disorders are notoriously difficult to diagnose and treat in the outpatient primary care setting, which is why mental health professionals will need to be a more integral part of the postpandemic treatment model and should be represented on the advisory board. Each year in the United States, there are more than 8 million doctors’ visits for depression, and more than half of these are in the primary care setting. Yet fewer than half of those patients leave with a diagnosis of depression or are treated for it.
Historically, screening for depression in the primary care setting is difficult given its broad presentation of symptoms, which include nonspecific physical complaints, such as digestive problems, headaches, insomnia, or general aches and pains. These shortcomings exist despite multiple changes in guidelines, such as regarding the use of self-screening tools and general screening for specific populations, such as postpartum women.
But screening alone has not been an effective strategy, especially when certain groups are less likely to be screened. These include older adults, Black persons, and men, all of whom are at higher risk for mortality after COVID-19. There is a failure to consistently apply standards of universal screening across all patient groups, and even if it occurs, there is a failure to establish reliable treatment and follow-up regimens. As clinicians, imagine how challenging diagnosis and treatment of more complicated psychiatric syndromes, such as somatoform disorder, will be in the primary care setting after the pandemic.
When almost two-thirds of symptoms in primary care are already “medically unexplained,” how do we expect primary care doctors to differentiate between those presenting with vague coronavirus-related “brain fog,” the run of the mill worrywart, and the 16%-34% with legitimate hypochondriasis of somatoform disorder who won’t improve without the involvement of a mental health provider?
A specialty in short supply
The mental health system we have now is inadequate for those who are currently diagnosed with mental disorders. Before the pandemic, emergency departments were boarding increasing numbers of patients with psychiatric illness because beds on inpatient units were unavailable. Individuals with insurance faced difficulty finding psychiatrists or psychotherapists who took insurance or who were availabile to accept new patients, given the growing shortage of providers in general. Community health centers continued to grapple with decreases in federal and state funding despite public political support for parity. Individuals with substance use faced few options for the outpatient, residential, or pharmacologic treatment that many needed to maintain sobriety.
Since the pandemic, we have seen rates of anxiety, depression, and suicidal thinking increase among adults and youth while many clinics have been forced to lay off employees, reduce services, or close their doors. As psychiatrists, we not only see the lack of treatment options for our patients but are forced to find creative solutions to meet their needs. How are we supposed to adapt (or feel confident) when individuals with or without previous mental illness face downstream consequences after COVID-19 when not one of our own is represented in the advisory board? How can we feel confident that downstream solutions acknowledge and address the intricacy of the behavioral health system that we, as mental health providers, know so intimately?
And what about the cumulative impact of everything else that has happened in 2020 in addition to the pandemic?! Although cataloging the various negative events that have happened this year is beyond the scope of this discussion, such lists have been compiled by the mainstream media and include the Australian brush fires, the crisis in Armenia, racial protests, economic uncertainties, and the run-up to and occurrence of the 2020 presidential election. Research is solid in its assertion that chronic stress can disturb our immune and cardiovascular systems, as well as mental health, leading to depression or anxiety. As a result of the pandemic itself, plus the events of this year, mental health providers are already warning not only of the current trauma underlying our day-to-day lives but also that of years to come.
More importantly, healthcare providers, both those represented by members of the advisory board and those who are not, are not immune to these issues. Before the pandemic, rates of suicide among doctors were already above average compared with other professions. After witnessing death repeatedly, self-isolation, the risk for infection to family, and dealing with the continued resistance to wearing masks, who knows what the eventual psychological toll our medical workforce will be?
Mental health providers have stepped up to the plate to provide care outside of traditional models to meet the needs that patients have now. One survey found that 81% of behavioral health providers began using telehealth for the first time in the past 6 months, owing to the COVID-19 pandemic. If not for the sake of the mental health of the Biden-Harris advisory board members themselves, who as doctors are likely to downplay the impact when struggling with mental health concerns in their own lives, a mental health provider deserves a seat at the table.
Plus, the outcomes speak for themselves when behavioral health providers collaborate with primary care providers to give treatment or when mental health experts are members of health crisis teams. Why wouldn’t the same be true for the Biden-Harris advisory board?
Kali Cyrus, MD, MPH, is an assistant professor of psychiatry and behavioral medicine at the Johns Hopkins School of Medicine, Baltimore, Maryland. She sees patients in private practice and offers consultation services in diversity strategy. Ranna Parekh, MD, MPH, is past deputy medical director and director of diversity and health equity for the American Psychiatric Association. She is currently a consultant psychiatrist at the Massachusetts General Hospital, Boston, and the chief diversity and inclusion officer at the American College of Cardiology.
A version of this article originally appeared on Medscape.com.
Moderna filing for FDA emergency COVID-19 vaccine approval, reports 94.1% efficacy
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
Blood glucose on admission predicts COVID-19 severity in all
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Approval of COVID-19 vaccines will change nature of clinical trials
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
Immune checkpoint inhibitors don’t increase COVID-19 incidence or mortality, studies suggest
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
FROM SITC 2020
CDC panel delves into priorities for COVID vaccine distribution
On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.
The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.
An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.
ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.
“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”
There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.
But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.
ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.
In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.
ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.
“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.
ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.
“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.
Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.
“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
Broader access
Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.
The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.
Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.
Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.
At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.
In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.
“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”
In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.
“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.
Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.
“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.
Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.
There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.
Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.
The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.
“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.
Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.
“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.
ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.
“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.
This article first appeared on Medscape.com.
On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.
The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.
An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.
ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.
“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”
There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.
But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.
ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.
In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.
ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.
“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.
ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.
“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.
Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.
“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
Broader access
Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.
The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.
Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.
Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.
At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.
In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.
“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”
In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.
“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.
Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.
“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.
Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.
There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.
Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.
The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.
“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.
Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.
“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.
ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.
“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.
This article first appeared on Medscape.com.
On Monday, members of an influential federal panel delved into the challenges ahead in deciding who will get the first doses of COVID-19 vaccines, including questions about which healthcare workers need those initial vaccinations the most.
The Advisory Committee on Immunization Practices (ACIP) of the Centers for Disease Control and Prevention (CDC) did not take any votes or seek to establish formal positions. Instead, the meeting served as a forum for experts to discuss the thorny issues ahead. The US Food and Drug Administration (FDA) could make a decision next month regarding clearance for the first COVID-19 vaccine.
An FDA advisory committee will meet December 10 to review the request for emergency use authorization (EUA) of a COVID-19 vaccine from Pfizer, in partnership with BioNTech. Moderna Inc said on November 16 that it expects to soon ask the FDA for an EUA of its rival COVID vaccine.
ACIP will face a two-part task after the FDA clears COVID-19 vaccines, said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases. ACIP will need to first decide whether to recommend use of the vaccine and then address the “complicated and difficult” question of which groups should get the initial limited quantities.
“There aren’t any perfect decisions,” she told the ACIP members. “I know this is something that most of you didn’t anticipate doing, making these kinds of huge decisions in the midst of a pandemic.”
There has been considerable public discussion of prioritization of COVID-19 vaccines, including a set of recommendations offered by a special committee created by the National Academies of Sciences, Engineering and Medicine. In addition, CDC staff and members of ACIP outlined what they termed the “four ethical principles” meant to guide these decisions in a November 23 report in the agency’s Morbidity and Mortality Weekly Report. These four principles are to maximize benefits and minimize harms; promote justice; mitigate health inequities; and promote transparency.
But as the issuing of the first EUA nears, it falls to ACIP to move beyond endorsing broad goals. The panel will need to make decisions as to which groups will have to wait for COVID-19 vaccines.
ACIP members on Monday delved into these kinds of more detailed questions, using a proposed three-stage model as a discussion point.
In phase 1a of this model, healthcare workers and residents of long-term care facilities would be the first people to be vaccinated. Phase 1b would include those deemed essential workers, including police officers, firefighters, and those in education, transportation, food, and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years and older.
ACIP member Grace M. Lee, MD, MPH, of Stanford University, Stanford, California, questioned whether healthcare workers who are not seeing patients in person should wait to get the vaccines. There has been a marked rise in the use of telehealth during the pandemic, which has spared some clinicians from in-person COVID-19 patient visits in their practices.
“Close partnership with our public health colleagues will be critically important to make sure that we are not trying to vaccinate 100% of our healthcare workforce, if some proportion of our workforce can work from home,” Lee said.
ACIP member Pablo Sánchez, MD, of the Research Institute at Nationwide Children’s Hospital in Columbus, Ohio, concurred. Some clinicians, he noted, may have better access to personal protective equipment than others, he said.
“Unfortunately, not all healthcare workers are equal in terms of risk,” Sánchez said. “Within institutions, we’re going to have to prioritize which ones will get” the vaccine.
Clinicians may also make judgments about their own risk and need for early access to COVID-19 vaccinations, Sánchez said.
“I’m 66, and I’d rather give it to somebody much older and sicker than me,” he said.
Broader access
Fairly large populations will essentially be competing for limited doses of the first vaccines to reach the market.
The overlap is significant in the four priority groups put forward by CDC. The CDC staff estimated that about 21 million people would fall into the healthcare personnel category, which includes hospital staff, pharmacists, and those working in long-term care facilities. There are about 87 million people in the essential workers groups. More than 100 million adults in the United States, such as those with diabetes and cancers, fall into the high-risk medical conditions group. Another 53 million people are aged 65 and older.
Department of Health and Human Services Secretary Alex Azar on November 18 said the federal government expects to have about 40 million doses of these two vaccines by the end of December, which is enough to provide the two-dose regimen for about 20 million. If all goes as expected, Pfizer and Moderna will ramp up production.
Moderna has said that it expects by the end of this year to have approximately 20 million doses of its vaccine ready to ship in the United States and that it is on track to manufacture 500 million to 1 billion doses globally in 2021. Pfizer and BioNTech have said they expect to produce globally up to 50 million doses in 2020 and up to 1.3 billion doses by the end of 2021.
At the Monday meeting, several ACIP panelists stressed the need to ensure that essential workers get early doses of vaccines.
In many cases, these workers serve in jobs with significant public interaction and live in poor communities. They put themselves and their families at risk. Many of them lack the resources to take precautions available to those better able to isolate, said ACIP member Beth Bell, MD, MPH, of the University of Washington, Seattle, Washington.
“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance,” she said. “Recognizing that not all of them may want to be vaccinated at this stage, we need to provide them with the opportunity early on in the process.”
In Bell’s view, the initial rollout of COVID-19 vaccines will send an important message about sharing this resource.
“If we’re serious about valuing equity, we need to have that baked in early on in the vaccination program,” she said.
Bell also said she was in favor of including people living in nursing homes in the initial wave of vaccinations. Concerns were raised about the frailty of this population.
“Given the mortality impact on the healthcare system from the number of nursing home residents that have been dying, I think on balance it makes sense to include them in phase 1a,” Bell said.
Other ACIP panelists said missteps with early vaccination of people in nursing homes could undermine faith in the treatments. Because of the ages and medical conditions of people in nursing homes, many of them may die after receiving the COVID-19 vaccine. Such deaths would not be associated with vaccine, but the medical community would not yet have evidence to disprove a connection.
There could be a backlash, with people falsely linking the death of a grandparent to the vaccine.
Fellow ACIP member Robert L. Atmar, MD, Baylor College of Medicine, Houston, Texas, was among those who had raised concerns about including people living in long-term care facilities in phase 1a. He said there are not yet enough data to judge the balance of benefits and harms of vaccination for this population.
The Pfizer and Moderna vaccines are “reactagenic,” meaning people may not feel well in the days after receiving the shots. The symptoms could lead to additional health evaluations of older people in nursing homes as clinicians try to figure out whether the patient’s reactions to the vaccine are caused by some condition or infection, Atmar said.
“Those of us who see these patients in the hospital recognize that there are often medical interventions that are done in the pursuit of a diagnosis, of a change in clinical status, that in and of themselves can lead to harm,” Atmar said.
Clinicians likely will have to encourage their patients of all ages to receive second doses of COVID-19 vaccines, despite the malaise they may provoke.
“We really need to make patients aware that this is not going to be a walk in the park. I mean, they’re going to know they had a vaccine, they’re probably not going to feel wonderful, but they’ve got to come back for that second dose,” said Sandra Adamson Fryhofer, MD, who represented the American Medical Association.
ACIP is expected to meet again to offer specific recommendations on the Pfizer and Moderna vaccines. ACIP’s recommendations trigger reimbursement processes, Azar said at a Tuesday press conference. ACIP’s work will inform decisions made by the federal government and governors about deploying shipments of COVID-19 vaccines, he said.
“At the end of the day, that is a decision, though, of the US government to make, which is where to recommend the prioritization,” Azar said. “It will be our nation’s governors in implementing the distribution plans to tell us” where to ship the vaccine.
This article first appeared on Medscape.com.
Add delirium to checklist of COVID-19 symptoms in seniors
Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.
Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.
Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).
“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.
“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.
“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.
Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.
That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.
“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.
In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.
According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.
Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.
“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
Study details
For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).
Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.
The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.
Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.
The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.
Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.
Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.
“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.
In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.
Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.
“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.
Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.
The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.
Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.
Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).
“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.
“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.
“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.
Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.
That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.
“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.
In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.
According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.
Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.
“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
Study details
For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).
Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.
The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.
Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.
The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.
Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.
Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.
“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.
In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.
Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.
“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.
Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.
The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
Delirium should be included on checklists of the presenting signs and symptoms of COVID-19, particularly in elderly adults, according to a multicenter study of seniors visiting emergency departments.
Overall, 28% of the 817 older adults who presented to the emergency department and were diagnosed with COVID-19 had delirium, according to a study published online November 19 in JAMA Network Open. Moreover, 16% of these patients had delirium that was not accompanied by typical symptoms or signs of SARS-CoV-2 infection.
Among patients with delirium, there was a greater probability of admission to the intensive care unit compared with patients who presented without delirium (adjusted relative risk [aRR], 1.67; 95% CI, 1.30 – 2.15), as well as a greater probability of death (aRR, 1.24; 95% CI, 1.00 – 1.55).
“These findings suggest the clinical importance of including delirium on checklists of presenting signs and symptoms of COVID-19 that guide screening, testing, and evaluation,” write Maura Kennedy, MD, MPH, and colleagues.
“I was absolutely seeing cases of delirium where there were no other symptoms of COVID-19, but we didn’t have lot of data on the frequency of this,” explained Kennedy, an emergency department physician at Massachusetts General Hospital and an assistant professor of emergency medicine at Harvard Medical School, Boston.
“And the rate was somewhat surprising compared with that seen in non-COVID studies of delirium, but then our study population was more at risk, coming from long-term care facilities and having prior stroke or dementia,” she said. The most common form of delirium was hypoactive sleepiness and nonresponsiveness, although hyperactivity and agitation were also seen.
Kennedy thinks the addition of delirium as a common presenting symptom to diagnostic checklists would prevent some cases from being missed and allow earlier identification and management of COVID-19 patients at high risk for poor outcomes. “We certainly don’t want to send them back undiagnosed to a long-term care facility or promote transmission within the hospital,” she told Medscape Medical News.
That step has already been implemented in some US centers. “Delirium is something we’ve been looking at since the early summer,” said geriatrician Angela Catic, MD, an assistant professor at Baylor College of Medicine’s Huffington Center on Aging and the Michael E. DeBakey VA Medical Center, Houston, Texas.
“If we see delirium, we’re looking for COVID-19,” said Catic, who was not involved in the study.
In Catic’s experience, it is “not at all atypical” to see patients whose only symptom of COVID-19 is delirium. As with other infections and diseases, “the aging brain is incredibly vulnerable,” she said.
According to William W. Hung, MD, MPH, an assistant professor of geriatrics and palliative medicine at the Icahn School of Medicine at Mount Sinai, New York City, delirium is “generally a common sign of something seriously wrong” in older adults. “In the case of COVID-19, low oxygenation caused by the infection may play a role,” he told Medscape Medical News. Although he agreed that delirium should be included in the differential diagnosis of COVID-19, how frequently it is the only symptom at presentation would need to be determined in a considerably larger population, he said.
Joining the company of those observing this COVID-19 manifestation is Christopher R. Carpenter, MD, a professor of emergency medicine at Washington University in St. Louis, St. Louis, Missouri. He was not a participant in the current study.
“I have absolutely seen and documented delirium as the presenting complaint in older adult patients who were ultimately diagnosed with SARS-CoV-2, and since March, I contemplate SARS-CoV-2 each time I identify delirium,” Carpenter told Medscape Medical News. “Honestly, I ― and most of my colleagues ― are considering SARS-CoV-2 for a range of symptoms and complaints these days, because of the odd presentations we’ve all encountered.”
Study details
For the study, Kennedy and colleagues enrolled consecutive adults aged 65 years and older who were diagnosed with active COVID-19 and who presented to emergency departments at seven centers in Massachusetts, Maine, Connecticut, Michigan, and North Carolina on or after March 13, 2020. Active infection with SARS-CoV-2 was determined on the basis of results of nasal swab polymerase chain reaction tests (99% of cases) or the appearance and distribution of ground-glass opacities on chest radiography or CT (1%).
Of the 817 patients enrolled, 386 (47%) were men, 493 (62%) were White, 215 (27%) were Black, and 54 (7%) were Hispanic or Latinx. The mean age of patients was 77.7 years (standard deviation, 8.2). Their age placed them at risk for chronic comorbidities and cognitive problems; indeed, 15% had at least four chronic conditions, and 30% had existing cognitive impairment.
The authors note that among the 226 patients (28%) who had delirium at presentation, 60 (27%) had experienced delirium for a duration of 2 to 7 days.
Additionally, of the 226 patients who exhibited delirium as a primary symptom, 84 (37%) showed no typical COVID-19 symptoms or signs, such as cough, fever, or shortness of breath.
The presence of delirium did not correlate with any of the typical COVID-19 symptoms in particular; Kennedy noted that only 56% of patients in the cohort had a fever at presentation.
Delirium at presentation was significantly associated with a median hospital stay of more than 8 days (aRR, 1.14; 95% CI, .97 – 1.35) and a greater risk for discharge to a rehabilitation facility (aRR, 1.55; 95% CI, 1.07 – 2.26). Factors associated with delirium included age older than 75 years, residence in a nursing home or assisted-living facility, previous use of psychoactive medications, vision impairment, hearing impairment, stroke, and Parkinson’s disease.
Kennedy noted that the rate of delirium observed in this study is much higher than that generally reported in emergency department studies conducted before the COVID-19 pandemic. In those studies, the delirium rate ranged from 7% to 20%. The associated risk factors, however, are comparable.
“Mounting evidence supports the high occurrence of delirium and other neuropsychiatric manifestations with COVID-19, with previously reported rates of 22% to 33% among hospitalized patients,” Kennedy and associates write.
In Carpenter’s opinion, the development of incident delirium while receiving care in the emergency department, as opposed to delirium at the time of presentation, has been exacerbated by the no-visitor policies mandated by the pandemic, which have prevented visits even from personal caregivers of patients with moderate to severe dementia. “Although healthcare systems need to be cognizant of the risk of spread to uninfected caregivers, there’s a risk-benefit balance that must be found, because having one caregiver at the bedside can prevent delirium in cognitively impaired patients,” said Carpenter, who was not involved in the current study.
Among the barriers to improving the situation, Carpenter cited the lack of routine delirium screening and the absence of high-quality evidence to support emergency department interventions to mitigate delirium.
“Layer those challenges on top of COVID-19’s rapidly evolving diagnostic landscape, frequent atypical presentations, and asymptomatic carriers across all age groups and the negative impact of delirium is magnified,” Carpenter said.
Once elderly patients are hospitalized, Kennedy recommends the nonpharmacologic guidelines of the Hospital Elder Life Program for reducing delirium risk. Recommendations include the providing of adequate sleep, hydration, and nutrition, as well as function restoration, precipitant avoidance, and reorientation.
The study was supported in part by the National Institute on Aging and the Massachusetts Medical School. The authors, Carpenter, Hung, and Catic have disclosed no relevant financial relationships.
This article first appeared on Medscape.com.
COVID-19 cases in children continue to set records
As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.
Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.
In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.
The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.
Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.
Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.
As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.
Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.
In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.
The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.
Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.
Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.
As far as the pandemic is concerned, it seems like a pretty small thing. A difference of just 0.3%. Children now represent 11.8% of all COVID-19 cases that have occurred since the beginning of the pandemic, compared with 11.5% 1 week ago, according to the American Academy of Pediatrics and the Children’s Hospital Association.
Hiding behind that 0.3%, however, is a much larger number: 144,145. That is the number of new child cases that occurred during the week that ended Nov. 19, and it’s the highest weekly figure yet, eclipsing the previous high of 111,946 from the week of Nov. 12, the AAP and the CHA said in their latest COVID-19 report. For the week ending Nov. 19, children represented 14.1% of all new cases, up from 14.0% the week before.
In the United States, more than 1.18 million children have been infected by the coronavirus since the beginning of the pandemic, with the total among all ages topping 10 million in 49 states (New York is not providing age distribution), the District of Columbia, New York City, Puerto Rico, and Guam, the AAP/CHA data show. That works out to 11.8% of all cases.
The overall rate of child COVID-19 cases is now up to 1,573 per 100,000 children nationally, with considerable variation seen among the states. The lowest rates can be found in Vermont (344 per 100,000), Maine (452), and Hawaii (675), and the highest in North Dakota (5,589), South Dakota (3,993), and Wisconsin (3,727), the AAP and CHA said in the report.
Comparisons between states are somewhat problematic, though, because “each state makes different decisions about how to report the age distribution of COVID-19 cases, and as a result the age range for reported cases varies by state. … It is not possible to standardize more detailed age ranges for children based on what is publicly available from the states at this time,” the two organizations noted.
Five more COVID-19–related deaths in children were reported during the week of Nov. 19, bringing the count to 138 and holding at just 0.06% of the total for all ages, based on data from 43 states and New York City. Children’s share of hospitalizations increased slightly in the last week, rising from 1.7% to 1.8% in the 24 states (and NYC) that are reporting such data. The total number of child hospitalizations in those jurisdictions is just over 6,700, the AAP and CHA said.
Mortality rate of SARS-CoV-2 for similar patients is declining over time
Clinical question: Is the observed drop in COVID-19 mortality caused by changing demographics or improvements in patient care?
Background: At the start of the pandemic, COVID-19 had high mortality rates (6.9% in April according to the U.S. Centers for Disease Control and Prevention). More recently, the mortality rate had decreased to 1.9% of diagnosed cases at the end of September 2020. Concurrently, the median age of confirmed cases dropped as well, from 46 to 38 years, and availability of testing has expanded. It remains unclear whether the drop in mortality rate is because of affected patients with fewer comorbidities, less symptomatic patients, or improvements in clinical care.
Study design: Retrospective cohort study.
Setting: Large urban academic health system.
Synopsis: Researchers analyzed admissions from March 1 through Aug. 31, 2020, to NYU Langone Health System in New York of patients older than 18 years with laboratory-confirmed infection with SARS-CoV-2 during the hospitalization or in the preceding 2 weeks. In total, 5,118 patients qualified for analysis, of which 53% were hospitalized during March and April. Two separate multivariate logistic regression models for mortality were created based on patient demographics, comorbidities, and presenting vital signs and lab-result abnormalities. In the first model, the month of admission was not included, and the standardized mortality ratio (SMR) – the ratio of the sum of observed and expected deaths – for each month was obtained. In the second model, the month of admission was included as a covariate, and the average marginal effect (AME) – the difference in probability of death or discharge to hospice between March and a subsequent time period for equivalent patients – was calculated. The SMR declined progressively over time from 1.26 (95% confidence interval, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August. When accounting for demographic and clinical severity changes, the adjusted AME declined every subsequent month after March reaching a maximum of 18.2 (95% CI, 12.0-24.4) percentage point decrease in probability of death in August.
Bottom line: Mortality from SARS-CoV-2 was significantly lower at the end of the 6-month period when adjusted for demographic and clinical factors for patients admitted to a single health care system in the United States.
Citation: Horwitz LI et al. Trends in COVID-19 Risk-Adjusted Mortality Rates. J Hosp Med. 2020 Oct 23. doi: 10.12788/jhm.3552
Dr. Halpern is a med-peds hospitalist at Brigham and Women’s Hospital in Boston.
Clinical question: Is the observed drop in COVID-19 mortality caused by changing demographics or improvements in patient care?
Background: At the start of the pandemic, COVID-19 had high mortality rates (6.9% in April according to the U.S. Centers for Disease Control and Prevention). More recently, the mortality rate had decreased to 1.9% of diagnosed cases at the end of September 2020. Concurrently, the median age of confirmed cases dropped as well, from 46 to 38 years, and availability of testing has expanded. It remains unclear whether the drop in mortality rate is because of affected patients with fewer comorbidities, less symptomatic patients, or improvements in clinical care.
Study design: Retrospective cohort study.
Setting: Large urban academic health system.
Synopsis: Researchers analyzed admissions from March 1 through Aug. 31, 2020, to NYU Langone Health System in New York of patients older than 18 years with laboratory-confirmed infection with SARS-CoV-2 during the hospitalization or in the preceding 2 weeks. In total, 5,118 patients qualified for analysis, of which 53% were hospitalized during March and April. Two separate multivariate logistic regression models for mortality were created based on patient demographics, comorbidities, and presenting vital signs and lab-result abnormalities. In the first model, the month of admission was not included, and the standardized mortality ratio (SMR) – the ratio of the sum of observed and expected deaths – for each month was obtained. In the second model, the month of admission was included as a covariate, and the average marginal effect (AME) – the difference in probability of death or discharge to hospice between March and a subsequent time period for equivalent patients – was calculated. The SMR declined progressively over time from 1.26 (95% confidence interval, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August. When accounting for demographic and clinical severity changes, the adjusted AME declined every subsequent month after March reaching a maximum of 18.2 (95% CI, 12.0-24.4) percentage point decrease in probability of death in August.
Bottom line: Mortality from SARS-CoV-2 was significantly lower at the end of the 6-month period when adjusted for demographic and clinical factors for patients admitted to a single health care system in the United States.
Citation: Horwitz LI et al. Trends in COVID-19 Risk-Adjusted Mortality Rates. J Hosp Med. 2020 Oct 23. doi: 10.12788/jhm.3552
Dr. Halpern is a med-peds hospitalist at Brigham and Women’s Hospital in Boston.
Clinical question: Is the observed drop in COVID-19 mortality caused by changing demographics or improvements in patient care?
Background: At the start of the pandemic, COVID-19 had high mortality rates (6.9% in April according to the U.S. Centers for Disease Control and Prevention). More recently, the mortality rate had decreased to 1.9% of diagnosed cases at the end of September 2020. Concurrently, the median age of confirmed cases dropped as well, from 46 to 38 years, and availability of testing has expanded. It remains unclear whether the drop in mortality rate is because of affected patients with fewer comorbidities, less symptomatic patients, or improvements in clinical care.
Study design: Retrospective cohort study.
Setting: Large urban academic health system.
Synopsis: Researchers analyzed admissions from March 1 through Aug. 31, 2020, to NYU Langone Health System in New York of patients older than 18 years with laboratory-confirmed infection with SARS-CoV-2 during the hospitalization or in the preceding 2 weeks. In total, 5,118 patients qualified for analysis, of which 53% were hospitalized during March and April. Two separate multivariate logistic regression models for mortality were created based on patient demographics, comorbidities, and presenting vital signs and lab-result abnormalities. In the first model, the month of admission was not included, and the standardized mortality ratio (SMR) – the ratio of the sum of observed and expected deaths – for each month was obtained. In the second model, the month of admission was included as a covariate, and the average marginal effect (AME) – the difference in probability of death or discharge to hospice between March and a subsequent time period for equivalent patients – was calculated. The SMR declined progressively over time from 1.26 (95% confidence interval, 1.15-1.39) in March to 0.38 (95% CI, 0.12-0.88) in August. When accounting for demographic and clinical severity changes, the adjusted AME declined every subsequent month after March reaching a maximum of 18.2 (95% CI, 12.0-24.4) percentage point decrease in probability of death in August.
Bottom line: Mortality from SARS-CoV-2 was significantly lower at the end of the 6-month period when adjusted for demographic and clinical factors for patients admitted to a single health care system in the United States.
Citation: Horwitz LI et al. Trends in COVID-19 Risk-Adjusted Mortality Rates. J Hosp Med. 2020 Oct 23. doi: 10.12788/jhm.3552
Dr. Halpern is a med-peds hospitalist at Brigham and Women’s Hospital in Boston.
FROM THE JOURNAL OF HOSPITAL MEDICINE