Covid ICYMI

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

Those with risk factors associated with COVID-19–related death post coronavirus vaccination should be considered a priority for COVID therapeutics and further booster doses say U.K. researchers.

The researchers have identified factors that put a person at greater risk of COVID-related death after they have completed both doses of the primary COVID vaccination schedule and a booster dose.

For their research, published in JAMA Network Open, researchers from the Office for National Statistics (ONS); Public Health Scotland; the University of Strathclyde, Glasgow; and the University of Edinburgh used data from the ONS Public linked data set combining the 2011 Census of England and covering 80% of the population of England. The study population included 19,473,570 individuals aged 18-100 years (mean age 60.8 years, 45.2% men, 92.0% White individuals) living in England who had completed both doses of their primary vaccination schedule and had received their mRNA booster 14 days or more prior to Dec. 31, 2021. The outcome of interest was time to death involving COVID-19 occurring between Jan. 1 and March 16, 2022.
 

Prioritization of booster doses and COVID-19 treatments

The authors highlighted how it had become “critical” to identify risk factors associated with COVID-19 death in those who had been vaccinated and pointed out that existing evidence was “based on people who have received one or two doses of a COVID-19 vaccine and were infected by the Alpha or Delta variant”. They emphasized that establishing which groups are at increased risk of COVID-19 death after receiving a booster is crucial for the “prioritization of further booster doses and access to COVID-19 therapeutics.”

During the study period the authors found that there were 4,781 (0.02%) deaths involving COVID-19 and 58,020 (0.3%) deaths from other causes. Of those who died of coronavirus, the mean age was 83.3 years, and the authors highlighted how “age was the most important characteristic” associated with the risk of postbooster COVID-19 death. They added that, compared with a 50-year-old, the HR for an 80-year-old individual was 31.3 (95% confidence interval, 26.1-37.6).

They found that women were at lower risk than men with an HR of 0.52 (95% CI, 0.49-0.55). An increased risk of COVID-19 death was also associated with living in a care home or in a socioeconomically deprived area.

Of note, they said that “there was no association between the risk of COVID-19 death and ethnicity, except for those of Indian background”, who they explained were at slightly elevated risk, compared with White individuals. However, they explained how the association with ethnicity was “unclear and differed from previous studies”, with their findings likely to be due “largely to the pronounced differences in vaccination uptake” between ethnic groups in previous studies.
 

Dementia concern

With regard to existing health conditions the authors commented that “most of the QCovid risk groups were associated with an increased HR of postbooster breakthrough death, except for of congenital heart disease, asthma, and prior fracture.”

Risk was particularly elevated, they said, for people with severe combined immunodeficiency (HR, 6.2; 95% CI, 3.3-11.5), and they also identified several conditions associated with HRs of greater than 3, including dementia.

In July, Alzheimer’s Research UK urged the Government to boost the development and deployment of new dementia treatments having found that a significant proportion of people who died of COVID-19 in 2020 and 2021 were living with the condition. At the time, data published by the ONS of deaths caused by coronavirus in England and Wales in 2021 showed dementia to be the second-most common pre-existing condition.

David Thomas, head of policy at Alzheimer’s Research UK, said: “We’ve known for some time that people with dementia have been hit disproportionately hard during the pandemic, but this new data serves as a stark reminder of the growing challenge we face in tackling the condition, and the urgent need to address it.”

The authors of the new research acknowledged the study’s limitations, notably that only data for the population living in England who were enumerated in the 2011 Census of England and Wales was included.

However, subpopulations “remain at increased risk of COVID-19 fatality” after receiving a booster vaccine during the Omicron wave, they pointed out.

“The subpopulations with the highest risk should be considered a priority for COVID-19 therapeutics and further booster doses,” they urged.

A version of this article first appeared on Medscape UK.

Experiencing psychological distress prior to becoming infected with SARS-CoV-2 is tied to an increased risk for post-COVID conditions often called “long COVID,” new research suggests.

In an analysis of almost 55,000 adult participants in three ongoing studies, having depression, anxiety, worry, perceived stress, or loneliness early in the pandemic, before SARS-CoV-2 infection, was associated with a 50% increased risk for developing long COVID. These types of psychological distress were also associated with a 15% to 51% greater risk for impairment in daily life among individuals with long COVID.

Psychological distress was even more strongly associated with developing long COVID than were physical health risk factors, and the increased risk was not explained by health behaviors such as smoking or physical comorbidities, researchers note.

“Our findings suggest the need to consider psychological health in addition to physical health as risk factors of long COVID-19,” lead author Siwen Wang, MD, postdoctoral fellow, department of nutrition, Harvard T. H. Chan School of Public Health, Boston, said in an interview.

“We need to increase public awareness of the importance of mental health and focus on getting mental health care for people who need it, increasing the supply of mental health clinicians and improving access to care,” she said.

The findings were published online in JAMA Psychiatry.
 

‘Poorly understood’

Postacute sequelae of SARS-CoV-2 (“long COVID”), which are “signs and symptoms consistent with COVID-19 that extend beyond 4 weeks from onset of infection” constitute “an emerging health issue,” the investigators write.

Dr. Wang noted that it has been estimated that 8-23 million Americans have developed long COVID. However, “despite the high prevalence and daily life impairment associated with long COVID, it is still poorly understood, and few risk factors have been established,” she said.

Although psychological distress may be implicated in long COVID, only three previous studies investigated psychological factors as potential contributors, the researchers note. Also, no study has investigated the potential role of other common manifestations of distress that have increased during the pandemic, such as loneliness and perceived stress, they add.

To investigate these issues, the researchers turned to three large ongoing longitudinal studies: the Nurses’ Health Study II (NSHII), the Nurses’ Health study 3 (NHS3), and the Growing Up Today Study (GUTS).

They analyzed data on 54,960 total participants (96.6% women; mean age, 57.5 years). Of the full group, 38% were active health care workers.

Participants completed an online COVID-19 questionnaire from April 2020 to Sept. 1, 2020 (baseline), and monthly surveys thereafter. Beginning in August 2020, surveys were administered quarterly. The end of follow-up was in November 2021.

The COVID questionnaires included questions about positive SARS-CoV-2 test results, COVID symptoms and hospitalization since March 1, 2020, and the presence of long-term COVID symptoms, such as fatigue, respiratory problems, persistent cough, muscle/joint/chest pain, smell/taste problems, confusion/disorientation/brain fog, depression/anxiety/changes in mood, headache, and memory problems.

Participants who reported these post-COVID conditions were asked about the frequency of symptoms and the degree of impairment in daily life.
 

Inflammation, immune dysregulation implicated?

The Patient Health Questionnaire–4 (PHQ-4) was used to assess for anxiety and depressive symptoms in the past 2 weeks. It consists of a two-item depression measure (PHQ-2) and a two-item Generalized Anxiety Disorder Scale (GAD-2).

Non–health care providers completed two additional assessments of psychological distress: the four-item Perceived Stress Scale and the three-item UCLA Loneliness Scale.

The researchers included demographic factors, weight, smoking status, marital status, and medical conditions, including diabetes, hypertension, hypercholesterolemia, asthma, and cancer, and socioeconomic factors as covariates.

For each participant, the investigators calculated the number of types of distress experienced at a high level, including probable depression, probable anxiety, worry about COVID-19, being in the top quartile of perceived stress, and loneliness.

During the 19 months of follow-up (1-47 weeks after baseline), 6% of respondents reported a positive result on a SARS-CoV-2 antibody, antigen, or polymerase chain reaction test.

Of these, 43.9% reported long-COVID conditions, with most reporting that symptoms lasted 2 months or longer; 55.8% reported at least occasional daily life impairment.

The most common post-COVID conditions were fatigue (reported by 56%), loss of smell or taste problems (44.6%), shortness of breath (25.5%), confusion/disorientation/ brain fog (24.5%), and memory issues (21.8%).

Among patients who had been infected, there was a considerably higher rate of preinfection psychological distress after adjusting for sociodemographic factors, health behaviors, and comorbidities. Each type of distress was associated with post-COVID conditions.

In addition, participants who had experienced at least two types of distress prior to infection were at nearly 50% increased risk for post–COVID conditions (risk ratio, 1.49; 95% confidence interval, 1.23-1.80).

Among those with post-COVID conditions, all types of distress were associated with increased risk for daily life impairment (RR range, 1.15-1.51).

Senior author Andrea Roberts, PhD, senior research scientist at the Harvard T. H. Chan School of Public Health, Boston, noted that the investigators did not examine biological mechanisms potentially underlying the association they found.

However, “based on prior research, it may be that inflammation and immune dysregulation related to psychological distress play a role in the association of distress with long COVID, but we can’t be sure,” Dr. Roberts said.
 

Contributes to the field

Commenting for this article, Yapeng Su, PhD, a postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, called the study “great work contributing to the long-COVID research field and revealing important connections” with psychological stress prior to infection.

Dr. Su, who was not involved with the study, was previously at the Institute for Systems Biology, also in Seattle, and has written about long COVID.

He noted that the “biological mechanism of such intriguing linkage is definitely the important next step, which will likely require deep phenotyping of biological specimens from these patients longitudinally.”

Dr. Wang pointed to past research suggesting that some patients with mental illness “sometimes develop autoantibodies that have also been associated with increased risk of long COVID.” In addition, depression “affects the brain in ways that may explain certain cognitive symptoms in long COVID,” she added.

More studies are now needed to understand how psychological distress increases the risk for long COVID, said Dr. Wang.

The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, the Dean’s Fund for Scientific Advancement Acceleration Award from the Harvard T. H. Chan School of Public Health, the Massachusetts Consortium on Pathogen Readiness Evergrande COVID-19 Response Fund Award, and the Veterans Affairs Health Services Research and Development Service funds. Dr. Wang and Dr. Roberts have reported no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Su reports no relevant financial relationships.

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

Experiencing psychological distress prior to becoming infected with SARS-CoV-2 is tied to an increased risk for post-COVID conditions often called “long COVID,” new research suggests.

In an analysis of almost 55,000 adult participants in three ongoing studies, having depression, anxiety, worry, perceived stress, or loneliness early in the pandemic, before SARS-CoV-2 infection, was associated with a 50% increased risk for developing long COVID. These types of psychological distress were also associated with a 15% to 51% greater risk for impairment in daily life among individuals with long COVID.

Psychological distress was even more strongly associated with developing long COVID than were physical health risk factors, and the increased risk was not explained by health behaviors such as smoking or physical comorbidities, researchers note.

“Our findings suggest the need to consider psychological health in addition to physical health as risk factors of long COVID-19,” lead author Siwen Wang, MD, postdoctoral fellow, department of nutrition, Harvard T. H. Chan School of Public Health, Boston, said in an interview.

“We need to increase public awareness of the importance of mental health and focus on getting mental health care for people who need it, increasing the supply of mental health clinicians and improving access to care,” she said.

The findings were published online in JAMA Psychiatry.
 

‘Poorly understood’

Postacute sequelae of SARS-CoV-2 (“long COVID”), which are “signs and symptoms consistent with COVID-19 that extend beyond 4 weeks from onset of infection” constitute “an emerging health issue,” the investigators write.

Dr. Wang noted that it has been estimated that 8-23 million Americans have developed long COVID. However, “despite the high prevalence and daily life impairment associated with long COVID, it is still poorly understood, and few risk factors have been established,” she said.

Although psychological distress may be implicated in long COVID, only three previous studies investigated psychological factors as potential contributors, the researchers note. Also, no study has investigated the potential role of other common manifestations of distress that have increased during the pandemic, such as loneliness and perceived stress, they add.

To investigate these issues, the researchers turned to three large ongoing longitudinal studies: the Nurses’ Health Study II (NSHII), the Nurses’ Health study 3 (NHS3), and the Growing Up Today Study (GUTS).

They analyzed data on 54,960 total participants (96.6% women; mean age, 57.5 years). Of the full group, 38% were active health care workers.

Participants completed an online COVID-19 questionnaire from April 2020 to Sept. 1, 2020 (baseline), and monthly surveys thereafter. Beginning in August 2020, surveys were administered quarterly. The end of follow-up was in November 2021.

The COVID questionnaires included questions about positive SARS-CoV-2 test results, COVID symptoms and hospitalization since March 1, 2020, and the presence of long-term COVID symptoms, such as fatigue, respiratory problems, persistent cough, muscle/joint/chest pain, smell/taste problems, confusion/disorientation/brain fog, depression/anxiety/changes in mood, headache, and memory problems.

Participants who reported these post-COVID conditions were asked about the frequency of symptoms and the degree of impairment in daily life.
 

Inflammation, immune dysregulation implicated?

The Patient Health Questionnaire–4 (PHQ-4) was used to assess for anxiety and depressive symptoms in the past 2 weeks. It consists of a two-item depression measure (PHQ-2) and a two-item Generalized Anxiety Disorder Scale (GAD-2).

Non–health care providers completed two additional assessments of psychological distress: the four-item Perceived Stress Scale and the three-item UCLA Loneliness Scale.

The researchers included demographic factors, weight, smoking status, marital status, and medical conditions, including diabetes, hypertension, hypercholesterolemia, asthma, and cancer, and socioeconomic factors as covariates.

For each participant, the investigators calculated the number of types of distress experienced at a high level, including probable depression, probable anxiety, worry about COVID-19, being in the top quartile of perceived stress, and loneliness.

During the 19 months of follow-up (1-47 weeks after baseline), 6% of respondents reported a positive result on a SARS-CoV-2 antibody, antigen, or polymerase chain reaction test.

Of these, 43.9% reported long-COVID conditions, with most reporting that symptoms lasted 2 months or longer; 55.8% reported at least occasional daily life impairment.

The most common post-COVID conditions were fatigue (reported by 56%), loss of smell or taste problems (44.6%), shortness of breath (25.5%), confusion/disorientation/ brain fog (24.5%), and memory issues (21.8%).

Among patients who had been infected, there was a considerably higher rate of preinfection psychological distress after adjusting for sociodemographic factors, health behaviors, and comorbidities. Each type of distress was associated with post-COVID conditions.

In addition, participants who had experienced at least two types of distress prior to infection were at nearly 50% increased risk for post–COVID conditions (risk ratio, 1.49; 95% confidence interval, 1.23-1.80).

Among those with post-COVID conditions, all types of distress were associated with increased risk for daily life impairment (RR range, 1.15-1.51).

Senior author Andrea Roberts, PhD, senior research scientist at the Harvard T. H. Chan School of Public Health, Boston, noted that the investigators did not examine biological mechanisms potentially underlying the association they found.

However, “based on prior research, it may be that inflammation and immune dysregulation related to psychological distress play a role in the association of distress with long COVID, but we can’t be sure,” Dr. Roberts said.
 

Contributes to the field

Commenting for this article, Yapeng Su, PhD, a postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, called the study “great work contributing to the long-COVID research field and revealing important connections” with psychological stress prior to infection.

Dr. Su, who was not involved with the study, was previously at the Institute for Systems Biology, also in Seattle, and has written about long COVID.

He noted that the “biological mechanism of such intriguing linkage is definitely the important next step, which will likely require deep phenotyping of biological specimens from these patients longitudinally.”

Dr. Wang pointed to past research suggesting that some patients with mental illness “sometimes develop autoantibodies that have also been associated with increased risk of long COVID.” In addition, depression “affects the brain in ways that may explain certain cognitive symptoms in long COVID,” she added.

More studies are now needed to understand how psychological distress increases the risk for long COVID, said Dr. Wang.

The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, the Dean’s Fund for Scientific Advancement Acceleration Award from the Harvard T. H. Chan School of Public Health, the Massachusetts Consortium on Pathogen Readiness Evergrande COVID-19 Response Fund Award, and the Veterans Affairs Health Services Research and Development Service funds. Dr. Wang and Dr. Roberts have reported no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Su reports no relevant financial relationships.

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

Experiencing psychological distress prior to becoming infected with SARS-CoV-2 is tied to an increased risk for post-COVID conditions often called “long COVID,” new research suggests.

In an analysis of almost 55,000 adult participants in three ongoing studies, having depression, anxiety, worry, perceived stress, or loneliness early in the pandemic, before SARS-CoV-2 infection, was associated with a 50% increased risk for developing long COVID. These types of psychological distress were also associated with a 15% to 51% greater risk for impairment in daily life among individuals with long COVID.

Psychological distress was even more strongly associated with developing long COVID than were physical health risk factors, and the increased risk was not explained by health behaviors such as smoking or physical comorbidities, researchers note.

“Our findings suggest the need to consider psychological health in addition to physical health as risk factors of long COVID-19,” lead author Siwen Wang, MD, postdoctoral fellow, department of nutrition, Harvard T. H. Chan School of Public Health, Boston, said in an interview.

“We need to increase public awareness of the importance of mental health and focus on getting mental health care for people who need it, increasing the supply of mental health clinicians and improving access to care,” she said.

The findings were published online in JAMA Psychiatry.
 

‘Poorly understood’

Postacute sequelae of SARS-CoV-2 (“long COVID”), which are “signs and symptoms consistent with COVID-19 that extend beyond 4 weeks from onset of infection” constitute “an emerging health issue,” the investigators write.

Dr. Wang noted that it has been estimated that 8-23 million Americans have developed long COVID. However, “despite the high prevalence and daily life impairment associated with long COVID, it is still poorly understood, and few risk factors have been established,” she said.

Although psychological distress may be implicated in long COVID, only three previous studies investigated psychological factors as potential contributors, the researchers note. Also, no study has investigated the potential role of other common manifestations of distress that have increased during the pandemic, such as loneliness and perceived stress, they add.

To investigate these issues, the researchers turned to three large ongoing longitudinal studies: the Nurses’ Health Study II (NSHII), the Nurses’ Health study 3 (NHS3), and the Growing Up Today Study (GUTS).

They analyzed data on 54,960 total participants (96.6% women; mean age, 57.5 years). Of the full group, 38% were active health care workers.

Participants completed an online COVID-19 questionnaire from April 2020 to Sept. 1, 2020 (baseline), and monthly surveys thereafter. Beginning in August 2020, surveys were administered quarterly. The end of follow-up was in November 2021.

The COVID questionnaires included questions about positive SARS-CoV-2 test results, COVID symptoms and hospitalization since March 1, 2020, and the presence of long-term COVID symptoms, such as fatigue, respiratory problems, persistent cough, muscle/joint/chest pain, smell/taste problems, confusion/disorientation/brain fog, depression/anxiety/changes in mood, headache, and memory problems.

Participants who reported these post-COVID conditions were asked about the frequency of symptoms and the degree of impairment in daily life.
 

Inflammation, immune dysregulation implicated?

The Patient Health Questionnaire–4 (PHQ-4) was used to assess for anxiety and depressive symptoms in the past 2 weeks. It consists of a two-item depression measure (PHQ-2) and a two-item Generalized Anxiety Disorder Scale (GAD-2).

Non–health care providers completed two additional assessments of psychological distress: the four-item Perceived Stress Scale and the three-item UCLA Loneliness Scale.

The researchers included demographic factors, weight, smoking status, marital status, and medical conditions, including diabetes, hypertension, hypercholesterolemia, asthma, and cancer, and socioeconomic factors as covariates.

For each participant, the investigators calculated the number of types of distress experienced at a high level, including probable depression, probable anxiety, worry about COVID-19, being in the top quartile of perceived stress, and loneliness.

During the 19 months of follow-up (1-47 weeks after baseline), 6% of respondents reported a positive result on a SARS-CoV-2 antibody, antigen, or polymerase chain reaction test.

Of these, 43.9% reported long-COVID conditions, with most reporting that symptoms lasted 2 months or longer; 55.8% reported at least occasional daily life impairment.

The most common post-COVID conditions were fatigue (reported by 56%), loss of smell or taste problems (44.6%), shortness of breath (25.5%), confusion/disorientation/ brain fog (24.5%), and memory issues (21.8%).

Among patients who had been infected, there was a considerably higher rate of preinfection psychological distress after adjusting for sociodemographic factors, health behaviors, and comorbidities. Each type of distress was associated with post-COVID conditions.

In addition, participants who had experienced at least two types of distress prior to infection were at nearly 50% increased risk for post–COVID conditions (risk ratio, 1.49; 95% confidence interval, 1.23-1.80).

Among those with post-COVID conditions, all types of distress were associated with increased risk for daily life impairment (RR range, 1.15-1.51).

Senior author Andrea Roberts, PhD, senior research scientist at the Harvard T. H. Chan School of Public Health, Boston, noted that the investigators did not examine biological mechanisms potentially underlying the association they found.

However, “based on prior research, it may be that inflammation and immune dysregulation related to psychological distress play a role in the association of distress with long COVID, but we can’t be sure,” Dr. Roberts said.
 

Contributes to the field

Commenting for this article, Yapeng Su, PhD, a postdoctoral researcher at the Fred Hutchinson Cancer Research Center in Seattle, called the study “great work contributing to the long-COVID research field and revealing important connections” with psychological stress prior to infection.

Dr. Su, who was not involved with the study, was previously at the Institute for Systems Biology, also in Seattle, and has written about long COVID.

He noted that the “biological mechanism of such intriguing linkage is definitely the important next step, which will likely require deep phenotyping of biological specimens from these patients longitudinally.”

Dr. Wang pointed to past research suggesting that some patients with mental illness “sometimes develop autoantibodies that have also been associated with increased risk of long COVID.” In addition, depression “affects the brain in ways that may explain certain cognitive symptoms in long COVID,” she added.

More studies are now needed to understand how psychological distress increases the risk for long COVID, said Dr. Wang.

The research was supported by grants from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institutes of Health, the Dean’s Fund for Scientific Advancement Acceleration Award from the Harvard T. H. Chan School of Public Health, the Massachusetts Consortium on Pathogen Readiness Evergrande COVID-19 Response Fund Award, and the Veterans Affairs Health Services Research and Development Service funds. Dr. Wang and Dr. Roberts have reported no relevant financial relationships. The other investigators’ disclosures are listed in the original article. Dr. Su reports no relevant financial relationships.

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

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

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

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

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

Comments from the White House this week suggesting a once-a-year COVID-19 shot for most Americans, “just like your annual flu shot,” were met with backlash from many who say COVID and influenza come from different viruses and need different schedules.

Remarks, from “capitulation” to too few data, hit the airwaves and social media.

Some, however, agree with the White House vision and say that asking people to get one shot in the fall instead of periodic pushes for boosters will raise public confidence and buy-in and reduce consumer confusion.  

Health leaders, including Bob Wachter, MD, chair of the department of medicine at the University of California, San Francisco, say they like the framing of the concept – that people who are not high-risk should plan each year for a COVID shot and a flu shot.

“Doesn’t mean we KNOW shot will prevent transmission for a year. DOES mean it’ll likely lower odds of SEVERE case for a year & we need strategy to bump uptake,” Dr. Wachter tweeted this week.

But the numbers of Americans seeking boosters remain low. Only one-third of all eligible people 50 years and older have gotten a second COVID booster, according to the Centers for Disease Control and Prevention. About half of those who got the original two shots got a first booster.

Meanwhile, the United States is still averaging about 70,000 new COVID cases and more than 300 deaths every day.

The suggested change in approach comes as Pfizer/BioNTech and Moderna roll out their new boosters that target Omicron subvariants BA.4 and BA.5 after the CDC recommended their use and the U.S. Food and Drug Administration approved emergency use authorization. 

“As the virus continues to change, we will now be able to update our vaccines annually to target the dominant variant,” President Joe Biden said in a statement promoting the yearly approach.
 

Some say annual shot premature

Other experts say it’s too soon to tell whether an annual approach will work.

“We have no data to support that current vaccines, including the new BA.5 booster, will provide durable protection beyond 4-6 months. It would be good to aspire to this objective, and much longer duration or protection, but that will likely require next generation and nasal vaccines,” said Eric Topol, MD, Medscape’s editor-in-chief and founder and director of the Scripps Research Translational Institute.

A report in Nature Reviews Immunology states, “Mucosal vaccines offer the potential to trigger robust protective immune responses at the predominant sites of pathogen infection” and potentially “can prevent an infection from becoming established in the first place, rather than only curtailing infection and protecting against the development of disease symptoms.”

Dr. Topol tweeted after the White House statements, “[An annual vaccine] has the ring of Covid capitulation.”

William Schaffner, MD, an infectious disease expert at Vanderbilt University, Nashville, Tenn., told this news organization that he cautions against interpreting the White House comments as official policy.

“This is the difficulty of having public health announcements come out of Washington,” he said. “They ought to come out of the CDC.”

He says there is a reasonable analogy between COVID and influenza, but warns, “don’t push the analogy.”

They are both serious respiratory viruses that can cause much illness and death in essentially the same populations, he notes. These are the older, frail people, people who have underlying illnesses or are immunocompromised.

Both viruses also mutate. But there the paths diverge.

“We’ve gotten into a pattern of annually updating the influenza vaccine because it is such a singularly seasonal virus,” Dr. Schaffner said. “Basically it disappears during the summer. We’ve had plenty of COVID during the summers.”

For COVID, he said, “We will need a periodic booster. Could this be annually? That would certainly make it easier.” But it’s too soon to tell, he said.

Dr. Schaffner noted that several manufacturers are working on a combined flu/COVID vaccine.
 

Just a ‘first step’ toward annual shot

The currently updated COVID vaccine may be the first step toward an annual vaccine, but it’s only the first step, Dr. Schaffner said. “We haven’t committed to further steps yet because we’re watching this virus.”

Syra Madad, DHSc, MSc, an infectious disease epidemiologist at Harvard University’s Belfer Center for Science and International Affairs, Cambridge, Mass., and the New York City hospital system, told this news organization that arguments on both sides make sense.

Having a single message once a year can help eliminate the considerable confusion involving people on individual timelines with different levels of immunity and separate campaigns for COVID and flu shots coming at different times of the year.

“Communication around vaccines is very muddled and that shows in our overall vaccination rates, particularly booster rates,” she says. “The overall strategy is hopeful and makes sense if we’re going to progress that way based on data.”

However, she said that the data are just not there yet to show it’s time for an annual vaccine. First, scientists will need to see how long protection lasts with the Omicron-specific vaccine and how well and how long it protects against severe disease and death as well as infection.

COVID is less predictable than influenza and the influenza vaccine has been around for decades, Dr. Madad noted. With influenza, the patterns are more easily anticipated with their “ladder-like pattern,” she said. “COVID-19 is not like that.”

What is hopeful, she said, “is that we’ve been in the Omicron dynasty since November of 2021. I’m hopeful that we’ll stick with that particular variant.”

Dr. Topol, Dr. Schaffner, and Dr. Madad declared no relevant financial relationships.

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

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

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

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

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

BARCELONA – Hospitalized patients in the ICU because of an acute COVID-19 infection had significantly fewer thrombotic events and complications when treated with full-dose anticoagulation, compared with patients who received standard-dose anticoagulation prophylaxis, but full-dose anticoagulation also triggered an excess of moderate and severe bleeding events, randomized trial results show.

The new findings from the COVID-PACT trial in an exclusively U.S.-based cohort of 382 on-treatment patients in the ICU with COVID-19 infection may lead to a change in existing guidelines, which currently recommend standard-dose prophylaxis based on results from prior head-to-head comparisons, such as guidelines posted March 2022 from the American Society of Hematology.

The new findings suggest “full-dose anticoagulation should be considered to prevent thrombotic complications in selected critically ill patients with COVID-19” after weighing an individual patient’s risk for both thrombotic events and bleeding, David D. Berg, MD, said at the annual congress of the European Society of Cardiology. Simultaneous with his report at the congress, the results also appeared online in the journal Circulation.

“What the results tell us is that full-dose anticoagulation in critically ill patients with COVID-19 is highly effective for reducing thrombotic complications,” said Dr. Berg, a cardiologist and critical care physician at Brigham and Women’s Hospital, Boston.

The report’s designated discussant agreed with Dr. Berg’s conclusions.
 

‘Need to replace the guidelines’

“We probably need to replace the guidelines,” said Eduardo Ramacciotti, MD, PhD, MPH, a professor of vascular surgery at Santa Casa School of Medicine, São Paulo. Dr. Ramacciotti praised the study’s design, the endpoints, and the fact that the design excluded patients at high risk for bleeding complications, particularly those with a fibrinogen level below 200 mg/dL (2 g/L).

But other experts questioned the significance of the COVID-PACT results given that the outcomes did not show that full-dose anticoagulation produced incremental improvement in patient survival.

“We should abandon the thought that intensified anticoagulation should be routine, because it did not overall increase the number of patients discharged from the hospital alive,” commented John W. Eikelboom, MBBS, a professor of hematology and thromboembolism at McMaster University, Hamilton, Ont.

“Preventing venous thrombosis is a good thing, but the money is in saving lives and stopping need for ventilation, and we haven’t been successful doing that with an antithrombotic strategy,” said Dr. Eikelboom. “It is useful to prevent venous thrombosis, but we need to look elsewhere to improve the outcomes of [critically ill] patients with COVID-19.”
 

Reducing thromboembolism is a ‘valid goal’

Dr. Berg took a different view. “It’s a valid goal to try to reduce venous thromboembolism complications,” the major benefit seen in his study, he said. “There is clinical significance to reducing thrombotic events in terms of how people feel, their functional status, and their complications. There are a lot of clinically relevant consequences of thrombosis beyond mortality.”

COVID-PACT ran at 34 U.S. centers from August 2020 to March 2022 but stopped short of its enrollment goal of 750 patients because of waning numbers of patients with COVID-19 admitted to ICUs. In addition to randomly assigning patients within 96 hours of their ICU admission to full-dose anticoagulation or to standard-dose antithrombotic prophylaxis, the study included a second, concurrent randomization to the antiplatelet agent clopidogrel (Plavix) or to no antiplatelet drug. Both randomizations used an open-label design.

The results failed to show a discernable effect from adding clopidogrel on both the primary efficacy and primary safety endpoints, adding to accumulated evidence that treatment with an antiplatelet agent, including aspirin, confers no antithrombotic benefit in patients with COVID-19.

The trial’s participants averaged 61 years old, 68% were obese, 59% had hypertension, and 32% had diabetes. The median time after ICU admission when randomized treatment began was 2.1 days, and researchers followed patients for a median of 13 days, including a median time on anticoagulation of 10.6 days.

The trial design allowed clinicians to use either low molecular weight heparin or unfractionated heparin for anticoagulation, and 82% of patients received low molecular weight heparin as their initial treatment. The prespecified design called for an on-treatment analysis because of an anticipated high crossover rate. During the trial, 34% of patients who started on the prophylactic dose switched to full dose, and 17% had the reverse crossover.
 

95% increased win ratio with full dose

The study’s primary efficacy endpoint used a win-ratio analysis that included seven different adverse outcomes that ranged from death from venous or arterial thrombosis to clinically silent deep vein thrombosis. Treatment with full-dose anticoagulation led to a significant 95% increase in win ratio.

Researchers also applied a more conventional time-to-first-event secondary efficacy analysis, which showed that full-dose anticoagulation cut the incidence of an adverse outcome by a significant 44% relative to prophylactic dosing.

The two study groups showed no difference in all-cause death rates. The efficacy advantage of the full-dose regimen was driven by reduced rates of venous thrombotic events, especially a reduction in clinically evident deep vein thrombotic events.

The primary safety endpoint was the rate of fatal or life-threatening bleeding episodes, and while life-threatening bleeds were numerically more common among the full-dose recipients (four events, compared with one event on prophylaxis dosing) the difference was not significant, and no patients died from a bleeding event.
 

More secondary safety bleeds

The safety difference showed up in a secondary measure of bleeding severity, the rate of GUSTO moderate or severe bleeds. These occurred in 15 of the full-dose recipients, compared with 1 patient on the prophylactic dose.

Dr. Berg highlighted that several prior studies have assessed various anticoagulation regimens in critically ill (ICU-admitted and on respiratory or cardiovascular support) patients with COVID-19. For example, two influential reports published in 2021 by the same team of investigators in the New England Journal of Medicine had sharply divergent results.

One multicenter study, which tested full-dose heparin against prophylactic treatment in more than 1,000 critically ill patients, was stopped prematurely because it had not shown a significant difference between the treatment arms. The second study, in more than 2,000 multicenter patients with COVID-19 who did not require critical-level organ support, showed clear superiority of the full-dose heparin regimen.

Notably, both previous studies used a different primary efficacy endpoint than the COVID-PACT study. The earlier reports both measured efficacy in terms of patients being alive and off organ support by 21 days from randomization.
 

Patients to exclude

Although Dr. Berg stressed the clear positive result, he also cautioned that they should not apply to patients excluded from the study: those with severe coagulopathies, those with severe thrombocytopenia, and patients already maintained on dual antiplatelet therapy. He also cautioned against using the full-dose strategy in elderly patients, because in COVID-PACT, those who developed bleeding complications tended to be older.

Dr. Berg also noted that heparin prophylaxis is a well-established intervention for ICU-admitted patients without COVID-19 for the purpose of preventing venous thromboembolisms without evidence that this approach reduces deaths or organ failure.

But he conceded that “the priority of treatment depends on whether it saves lives, so anticoagulation is probably not as high a priority as other effective treatments” that reduce mortality. “Preventing venous thromboembolism has rarely been shown to have a mortality benefit,” Dr. Berg noted.

COVID-PACT received no direct commercial funding. Dr. Berg has been a consultant to AstraZeneca, Mobility Bio, and Youngene Therapeutics, and he participated in a trial sponsored by Kowa. Dr. Ramacciotti has been a consultant to or speaker on behalf of Aspen, Bayer, Daiichi Sankyo, Mylan, Pfizer, and Sanofi, and he has received research support from Bayer, Esperon, Novartis, and Pfizer. Dr. Eikelboom has received honoraria and research support from Bayer.

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

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

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

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

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

A panel of infectious disease experts shared their take recently on the importance of the newly approved bivalent COVID-19 vaccines, why authorization without human data is not for them a cause for alarm, and what they are most optimistic about at this stage of the pandemic.

“I’m very encouraged by this new development,” Kathryn M. Edwards, MD, said during a media briefing sponsored by the Infectious Diseases Society of America (IDSA).

It makes sense to develop a vaccine that targets both the original SARS-CoV-2 strain and Omicron BA.4 and BA.5, she said. “It does seem that if you have a circulating strain BA.4 and BA.5, hitting it with the appropriate vaccine targeted for that is most immunogenic, certainly. We will hopefully see that in terms of effectiveness.”

Changing the vaccines at this point is appropriate, Walter A. Orenstein, MD, said. “One of our challenges is that this virus mutates. Our immune response is focused on an area of the virus that can change and be evaded,” said Dr. Orenstein, professor and associate director of the Emory Vaccine Center at Emory University, Atlanta.

“This is different than measles or polio,” he said. “But for influenza and now with SARS-CoV-2 ... we have to update our vaccines, because the virus changes.”
 

Man versus mouse

Dr. Edwards addressed the controversy over a lack of human data specific to these next-generation Pfizer/BioNTech and Moderna vaccines. “I do not want people to be unhappy or worried that the bivalent vaccine will act in a different way than the ones that we have been administering for the past 2 years.”

The Food and Drug Administration emergency use authorization may have relied primarily on animal studies, she said, but mice given a vaccine specific to BA.4 and BA.5 “have a much more robust immune response,” compared with those given a BA.1 vaccine.

Also, “over and over and over again we have seen with these SARS-CoV-2 vaccines that the mouse responses mirror the human responses,” said Dr. Edwards, scientific director of the Vanderbilt Vaccine Research Program at Vanderbilt University, Nashville, Tenn., and an IDSA fellow.

“Human data will be coming very soon to look at the immunogenicity,” she said.
 

A ‘glass half full’ perspective

When asked what they are most optimistic about at this point in the COVID-19 pandemic, Dr. Orenstein said, “I’m really positive in the sense that the vaccines we have are already very effective against severe disease, death, and hospitalization. I feel really good about that. And we have great tools.

“The bottom line for me is, I want to get it myself,” he said regarding the bivalent vaccine.

“There are a lot of things to be happy with,” Dr. Edwards said. “I’m kind of a glass-half-full kind of person.”

Dr. Edwards is confident that the surveillance systems now in place can accurately detect major changes in the virus, including new variants. She is also optimistic about the mRNA technology that allows rapid updates to COVID-19 vaccines.

Furthermore, “I’m happy that we’re beginning to open up – that we can go do different things that we have done in the past and feel much more comfortable,” she said.
 

More motivational messaging needed

Now is also a good time to renew efforts to get people vaccinated.

“We invested a lot into developing these vaccines, but I think we also need to invest in what I call ‘implementation science research,’ ” Dr. Orenstein said, the goal being to convince people to get vaccinated.

He pointed out that it’s vaccinations, not vaccines, that saves lives. “Vaccine doses that remain in the vial are 0% effective.

“When I was director of the United States’ immunization program at the CDC,” Dr. Orenstein said, “my director of communications used to say that you need the right message delivered by the right messenger through the right communications channel.”

Dr. Edwards agreed that listening to people’s concerns and respecting their questions are important. “We also need to make sure that we use the proper messenger, just as Walt said. Maybe the proper messenger isn’t an old gray-haired lady,” she said, referring to herself, “but it’s someone that lives in your community or is your primary care doctor who has taken care of you or your children for many years.”

Research on how to better motivate people to get vaccinated is warranted, Dr. Edwards said, as well as on “how to make sure that this is really a medical issue and not a political issue. That’s been a really big problem.”

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

Two large studies out of the United Kingdom and Norway show vitamin D supplementation has no benefit – as low dose, high dose, or in the form of cod liver oil supplementation – in preventing COVID-19 or acute respiratory tract infections, regardless of whether individuals are deficient or not.

copyright Joss/Fotolia.com

The studies, published in the BMJ, underscore that “vaccination is still the most effective way to protect people from COVID-19, and vitamin D and cod liver oil supplementation should not be offered to healthy people with normal vitamin D levels,” writes Peter Bergman, MD, of the Karolinska Institute, Stockholm, in an editorial published alongside the studies.

Suboptimal levels of vitamin D are known to be associated with an increased risk of acute respiratory infections, and some observational studies have linked low 25-hydroxyvitamin D (25[OH]D) with more severe COVID-19; however, data on a possible protective effect of vitamin D supplementation in preventing infection have been inconsistent.
 

U.K. study compares doses

To further investigate the relationship with infections, including COVID-19, in a large cohort, the authors of the first of the two BMJ studies, a phase 3 open-label trial, enrolled 6,200 people in the United Kingdom aged 16 and older between December 2020 and June 2021 who were not taking vitamin D supplements at baseline.

Half of participants were offered a finger-prick blood test, and of the 2,674 who accepted, 86.3% were found to have low concentrations of 25(OH)D (< 75 nmol/L). These participants were provided with vitamin D supplementation at a lower (800 IU/day; n = 1328) or higher dose (3,200 IU/day; n = 1,346) for 6 months. The other half of the group received no tests or supplements.

The results showed minimal differences between groups in terms of rates of developing at least one acute respiratory infection, which occurred in 5% of those in the lower-dose group, 5.7% in the higher-dose group, and 4.6% of participants not offered supplementation.

Similarly, there were no significant differences in the development of real-time PCR-confirmed COVID-19, with rates of 3.6% in the lower-dose group, 3.0% in the higher-dose group, and 2.6% in the group not offered supplementation.

The study is “the first phase 3 randomized controlled trial to evaluate the effectiveness of a test-and-treat approach for correction of suboptimal vitamin D status to prevent acute respiratory tract infections,” report the authors, led by Adrian R. Martineau, MD, PhD, of Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

While uptake and supplementation in the study were favorable, “no statistically significant effect of either dose was seen on the primary outcome of swab test, doctor-confirmed acute respiratory tract infection, or on the major secondary outcome of swab test-confirmed COVID-19,” they conclude.
 

Traditional use of cod liver oil of benefit?

In the second study, researchers in Norway, led by Arne Soraas, MD, PhD, of the department of microbiology, Oslo University Hospital, evaluated whether that country’s long-held tradition of consuming cod liver oil during the winter to prevent vitamin D deficiency could affect the development of COVID-19 or outcomes.

For the Cod Liver Oil for COVID-19 Prevention Study (CLOC), a large cohort of 34,601 adults with a mean age of 44.9 years who were not taking daily vitamin D supplements were randomized to receive 5 mL/day of cod liver oil, representing a surrogate dose of 400 IU/day of vitamin D (n = 17,278), or placebo (n = 17,323) for up to 6 months.

In contrast with the first study, the vast majority of patients in the CLOC study (86%) had adequate vitamin D levels, defined as greater than 50 nmol/L, at baseline.

Again, however, the results showed no association between increased vitamin D supplementation with cod liver oil and PCR-confirmed COVID-19 or acute respiratory infections, with approximately 1.3% in each group testing positive for COVID-19 over a median of 164 days.

Supplementation with cod liver oil was also not associated with a reduced risk of any of the coprimary endpoints, including other acute respiratory infections.

“Daily supplementation with cod liver oil, a low-dose vitamin D, eicosapentaenoic acid, and docosahexaenoic acid supplement, for 6 months during the SARS-CoV-2pandemic among Norwegian adults did not reduce the incidence of SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections,” the authors report.
 

Key study limitations

In his editorial, Dr. Bergman underscores the limitations of two studies – also acknowledged by the authors – including the key confounding role of vaccines that emerged during the studies.

“The null findings of the studies should be interpreted in the context of a highly effective vaccine rolled out during both studies,” Dr. Bergman writes.

In the U.K. study, for instance, whereas only 1.2% of participants were vaccinated at baseline, the rate soared to 89.1% having received at least one dose by study end, potentially masking any effect of vitamin D, he says.

Additionally, for the Norway study, Dr. Bergman notes that cod liver oil also contains a substantial amount of vitamin A, which can be a potent immunomodulator.

“Excessive intake of vitamin A can cause adverse effects and may also interfere with vitamin D-mediated effects on the immune system,” he writes.

With two recent large meta-analyses showing benefits of vitamin D supplementation to be specifically among people who are vitamin D deficient, “a pragmatic approach for the clinician could be to focus on risk groups” for supplementation, Dr. Bergman writes.

“[These include] those who could be tested before supplementation, including people with dark skin, or skin that is rarely exposed to the sun, pregnant women, and elderly people with chronic diseases.”

The U.K. trial was supported by Barts Charity, Pharma Nord, the Fischer Family Foundation, DSM Nutritional Products, the Exilarch’s Foundation, the Karl R. Pfleger Foundation, the AIM Foundation, Synergy Biologics, Cytoplan, the Clinical Research Network of the U.K. National Institute for Health and Care Research, the HDR UK BREATHE Hub, the U.K. Research and Innovation Industrial Strategy Challenge Fund, Thornton & Ross, Warburtons, Hyphens Pharma, and philanthropist Matthew Isaacs.

The CLOC trial was funded by Orkla Health, the manufacturer of the cod liver oil used in the trial. Dr. Bergman has reported no relevant financial relationships.

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

Two large studies out of the United Kingdom and Norway show vitamin D supplementation has no benefit – as low dose, high dose, or in the form of cod liver oil supplementation – in preventing COVID-19 or acute respiratory tract infections, regardless of whether individuals are deficient or not.

copyright Joss/Fotolia.com

The studies, published in the BMJ, underscore that “vaccination is still the most effective way to protect people from COVID-19, and vitamin D and cod liver oil supplementation should not be offered to healthy people with normal vitamin D levels,” writes Peter Bergman, MD, of the Karolinska Institute, Stockholm, in an editorial published alongside the studies.

Suboptimal levels of vitamin D are known to be associated with an increased risk of acute respiratory infections, and some observational studies have linked low 25-hydroxyvitamin D (25[OH]D) with more severe COVID-19; however, data on a possible protective effect of vitamin D supplementation in preventing infection have been inconsistent.
 

U.K. study compares doses

To further investigate the relationship with infections, including COVID-19, in a large cohort, the authors of the first of the two BMJ studies, a phase 3 open-label trial, enrolled 6,200 people in the United Kingdom aged 16 and older between December 2020 and June 2021 who were not taking vitamin D supplements at baseline.

Half of participants were offered a finger-prick blood test, and of the 2,674 who accepted, 86.3% were found to have low concentrations of 25(OH)D (< 75 nmol/L). These participants were provided with vitamin D supplementation at a lower (800 IU/day; n = 1328) or higher dose (3,200 IU/day; n = 1,346) for 6 months. The other half of the group received no tests or supplements.

The results showed minimal differences between groups in terms of rates of developing at least one acute respiratory infection, which occurred in 5% of those in the lower-dose group, 5.7% in the higher-dose group, and 4.6% of participants not offered supplementation.

Similarly, there were no significant differences in the development of real-time PCR-confirmed COVID-19, with rates of 3.6% in the lower-dose group, 3.0% in the higher-dose group, and 2.6% in the group not offered supplementation.

The study is “the first phase 3 randomized controlled trial to evaluate the effectiveness of a test-and-treat approach for correction of suboptimal vitamin D status to prevent acute respiratory tract infections,” report the authors, led by Adrian R. Martineau, MD, PhD, of Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

While uptake and supplementation in the study were favorable, “no statistically significant effect of either dose was seen on the primary outcome of swab test, doctor-confirmed acute respiratory tract infection, or on the major secondary outcome of swab test-confirmed COVID-19,” they conclude.
 

Traditional use of cod liver oil of benefit?

In the second study, researchers in Norway, led by Arne Soraas, MD, PhD, of the department of microbiology, Oslo University Hospital, evaluated whether that country’s long-held tradition of consuming cod liver oil during the winter to prevent vitamin D deficiency could affect the development of COVID-19 or outcomes.

For the Cod Liver Oil for COVID-19 Prevention Study (CLOC), a large cohort of 34,601 adults with a mean age of 44.9 years who were not taking daily vitamin D supplements were randomized to receive 5 mL/day of cod liver oil, representing a surrogate dose of 400 IU/day of vitamin D (n = 17,278), or placebo (n = 17,323) for up to 6 months.

In contrast with the first study, the vast majority of patients in the CLOC study (86%) had adequate vitamin D levels, defined as greater than 50 nmol/L, at baseline.

Again, however, the results showed no association between increased vitamin D supplementation with cod liver oil and PCR-confirmed COVID-19 or acute respiratory infections, with approximately 1.3% in each group testing positive for COVID-19 over a median of 164 days.

Supplementation with cod liver oil was also not associated with a reduced risk of any of the coprimary endpoints, including other acute respiratory infections.

“Daily supplementation with cod liver oil, a low-dose vitamin D, eicosapentaenoic acid, and docosahexaenoic acid supplement, for 6 months during the SARS-CoV-2pandemic among Norwegian adults did not reduce the incidence of SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections,” the authors report.
 

Key study limitations

In his editorial, Dr. Bergman underscores the limitations of two studies – also acknowledged by the authors – including the key confounding role of vaccines that emerged during the studies.

“The null findings of the studies should be interpreted in the context of a highly effective vaccine rolled out during both studies,” Dr. Bergman writes.

In the U.K. study, for instance, whereas only 1.2% of participants were vaccinated at baseline, the rate soared to 89.1% having received at least one dose by study end, potentially masking any effect of vitamin D, he says.

Additionally, for the Norway study, Dr. Bergman notes that cod liver oil also contains a substantial amount of vitamin A, which can be a potent immunomodulator.

“Excessive intake of vitamin A can cause adverse effects and may also interfere with vitamin D-mediated effects on the immune system,” he writes.

With two recent large meta-analyses showing benefits of vitamin D supplementation to be specifically among people who are vitamin D deficient, “a pragmatic approach for the clinician could be to focus on risk groups” for supplementation, Dr. Bergman writes.

“[These include] those who could be tested before supplementation, including people with dark skin, or skin that is rarely exposed to the sun, pregnant women, and elderly people with chronic diseases.”

The U.K. trial was supported by Barts Charity, Pharma Nord, the Fischer Family Foundation, DSM Nutritional Products, the Exilarch’s Foundation, the Karl R. Pfleger Foundation, the AIM Foundation, Synergy Biologics, Cytoplan, the Clinical Research Network of the U.K. National Institute for Health and Care Research, the HDR UK BREATHE Hub, the U.K. Research and Innovation Industrial Strategy Challenge Fund, Thornton & Ross, Warburtons, Hyphens Pharma, and philanthropist Matthew Isaacs.

The CLOC trial was funded by Orkla Health, the manufacturer of the cod liver oil used in the trial. Dr. Bergman has reported no relevant financial relationships.

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

Two large studies out of the United Kingdom and Norway show vitamin D supplementation has no benefit – as low dose, high dose, or in the form of cod liver oil supplementation – in preventing COVID-19 or acute respiratory tract infections, regardless of whether individuals are deficient or not.

copyright Joss/Fotolia.com

The studies, published in the BMJ, underscore that “vaccination is still the most effective way to protect people from COVID-19, and vitamin D and cod liver oil supplementation should not be offered to healthy people with normal vitamin D levels,” writes Peter Bergman, MD, of the Karolinska Institute, Stockholm, in an editorial published alongside the studies.

Suboptimal levels of vitamin D are known to be associated with an increased risk of acute respiratory infections, and some observational studies have linked low 25-hydroxyvitamin D (25[OH]D) with more severe COVID-19; however, data on a possible protective effect of vitamin D supplementation in preventing infection have been inconsistent.
 

U.K. study compares doses

To further investigate the relationship with infections, including COVID-19, in a large cohort, the authors of the first of the two BMJ studies, a phase 3 open-label trial, enrolled 6,200 people in the United Kingdom aged 16 and older between December 2020 and June 2021 who were not taking vitamin D supplements at baseline.

Half of participants were offered a finger-prick blood test, and of the 2,674 who accepted, 86.3% were found to have low concentrations of 25(OH)D (< 75 nmol/L). These participants were provided with vitamin D supplementation at a lower (800 IU/day; n = 1328) or higher dose (3,200 IU/day; n = 1,346) for 6 months. The other half of the group received no tests or supplements.

The results showed minimal differences between groups in terms of rates of developing at least one acute respiratory infection, which occurred in 5% of those in the lower-dose group, 5.7% in the higher-dose group, and 4.6% of participants not offered supplementation.

Similarly, there were no significant differences in the development of real-time PCR-confirmed COVID-19, with rates of 3.6% in the lower-dose group, 3.0% in the higher-dose group, and 2.6% in the group not offered supplementation.

The study is “the first phase 3 randomized controlled trial to evaluate the effectiveness of a test-and-treat approach for correction of suboptimal vitamin D status to prevent acute respiratory tract infections,” report the authors, led by Adrian R. Martineau, MD, PhD, of Barts and The London School of Medicine and Dentistry, Queen Mary University of London.

While uptake and supplementation in the study were favorable, “no statistically significant effect of either dose was seen on the primary outcome of swab test, doctor-confirmed acute respiratory tract infection, or on the major secondary outcome of swab test-confirmed COVID-19,” they conclude.
 

Traditional use of cod liver oil of benefit?

In the second study, researchers in Norway, led by Arne Soraas, MD, PhD, of the department of microbiology, Oslo University Hospital, evaluated whether that country’s long-held tradition of consuming cod liver oil during the winter to prevent vitamin D deficiency could affect the development of COVID-19 or outcomes.

For the Cod Liver Oil for COVID-19 Prevention Study (CLOC), a large cohort of 34,601 adults with a mean age of 44.9 years who were not taking daily vitamin D supplements were randomized to receive 5 mL/day of cod liver oil, representing a surrogate dose of 400 IU/day of vitamin D (n = 17,278), or placebo (n = 17,323) for up to 6 months.

In contrast with the first study, the vast majority of patients in the CLOC study (86%) had adequate vitamin D levels, defined as greater than 50 nmol/L, at baseline.

Again, however, the results showed no association between increased vitamin D supplementation with cod liver oil and PCR-confirmed COVID-19 or acute respiratory infections, with approximately 1.3% in each group testing positive for COVID-19 over a median of 164 days.

Supplementation with cod liver oil was also not associated with a reduced risk of any of the coprimary endpoints, including other acute respiratory infections.

“Daily supplementation with cod liver oil, a low-dose vitamin D, eicosapentaenoic acid, and docosahexaenoic acid supplement, for 6 months during the SARS-CoV-2pandemic among Norwegian adults did not reduce the incidence of SARS-CoV-2 infection, serious COVID-19, or other acute respiratory infections,” the authors report.
 

Key study limitations

In his editorial, Dr. Bergman underscores the limitations of two studies – also acknowledged by the authors – including the key confounding role of vaccines that emerged during the studies.

“The null findings of the studies should be interpreted in the context of a highly effective vaccine rolled out during both studies,” Dr. Bergman writes.

In the U.K. study, for instance, whereas only 1.2% of participants were vaccinated at baseline, the rate soared to 89.1% having received at least one dose by study end, potentially masking any effect of vitamin D, he says.

Additionally, for the Norway study, Dr. Bergman notes that cod liver oil also contains a substantial amount of vitamin A, which can be a potent immunomodulator.

“Excessive intake of vitamin A can cause adverse effects and may also interfere with vitamin D-mediated effects on the immune system,” he writes.

With two recent large meta-analyses showing benefits of vitamin D supplementation to be specifically among people who are vitamin D deficient, “a pragmatic approach for the clinician could be to focus on risk groups” for supplementation, Dr. Bergman writes.

“[These include] those who could be tested before supplementation, including people with dark skin, or skin that is rarely exposed to the sun, pregnant women, and elderly people with chronic diseases.”

The U.K. trial was supported by Barts Charity, Pharma Nord, the Fischer Family Foundation, DSM Nutritional Products, the Exilarch’s Foundation, the Karl R. Pfleger Foundation, the AIM Foundation, Synergy Biologics, Cytoplan, the Clinical Research Network of the U.K. National Institute for Health and Care Research, the HDR UK BREATHE Hub, the U.K. Research and Innovation Industrial Strategy Challenge Fund, Thornton & Ross, Warburtons, Hyphens Pharma, and philanthropist Matthew Isaacs.

The CLOC trial was funded by Orkla Health, the manufacturer of the cod liver oil used in the trial. Dr. Bergman has reported no relevant financial relationships.

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

Among men who have not been vaccinated against COVID-19, having low levels of testosterone may increase the risk of hospitalization from the disease – but hormone therapy appears to reduce the likelihood of severe COVID, researchers have found.

Low testosterone has long been linked to multiple chronic conditions, including obesity, heart disease, and type 2 diabetes, as well as acute conditions, such as heart attack and stroke. A study published earlier in the pandemic suggested that suppressing the sex hormone might protect against COVID-19. The new study, published in JAMA Network Open, is among the first to suggest a link between low testosterone and the risk for severe COVID.

Researchers at Washington University in St. Louis evaluated data from 723 unvaccinated men who had been infected with SARS-CoV-2. Of those, 116 had been diagnosed with hypogonadism, and 180 were receiving testosterone supplementation.

The study found that men whose testosterone levels were less than 200 ng/dL were 2.4 times more likely to experience a severe case of COVID-19 that required hospitalization than were those with normal levels of the hormone. The study accounted for the fact that participants with low testosterone were also more likely to have comorbidities such as diabetes and obesity.

Paresh Dandona, MD, PhD, distinguished professor of medicine and endocrinology at the State University of New York at Buffalo, called the findings “very exciting” and “fundamental.”

“In the world of hypogonadism, this is the first to show that low testosterone makes you vulnerable” to COVID, added Dr. Dandona, who was not involved with the research.

Men who were receiving hormone replacement therapy were at lower risk of hospitalization, compared with those who were not receiving treatment, the study found.

“Testosterone therapy seemed to negate the harmful effects of COVID,” said Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University and lead author of the study.

Approximately 50% more men have died from confirmed COVID-19 than women since the start of the pandemic, according to the Sex, Gender and COVID-19 Project. Previous findings suggesting that sex may be a risk factor for death from COVID prompted researchers to consider whether hormones may play a role in the increased risk among men and whether treatments that suppress androgen levels could cut hospitalizations, but researchers consistently found that androgen suppression was not effective.

“There are other reasons women might be doing better – they may have followed public health guidelines a lot better,” according to Abhinav Diwan, MD, professor of medicine at Washington University in St. Louis, who helped conduct the new study. “It may be chromosomal and not necessarily just hormonal. The differences between men and women go beyond one factor.”

According to the researchers, the findings do not suggest that hormone therapy be used as a preventive measure against COVID.

“We don’t want patients to get excited and start to ask their doctors for testosterone,” Dr. Dhindsa said.

However, viewing low testosterone as a risk factor for COVID could be considered a shift in thinking for some clinicians, according to Dr. Dandana.

“All obese and all [men with] type 2 diabetes should be tested for testosterone, which is the practice in my clinic right now, even if they have no symptoms,” Dr. Dandana said. “Certainly, those with symptoms [of low testosterone] but no diagnosis, they should be tested, too.”

Participants in the study were infected with SARS-CoV-2 early in 2020, before vaccines were available. The researchers did not assess whether the rate of hospitalizations among participants with low testosterone would be different had they been vaccinated.

“Whatever benefits we saw with testosterone might be minor compared to getting the vaccine,” Dr. Dhindsa said.

Dr. Diwan agreed. “COVID hospitalization continues to be a problem, the strains are evolving, and new vaccines are coming in,” he said. “The bottom line is to get vaccinated.”

Dr. Dhindsa has received personal fees from Bayer and Acerus Pharmaceuticals and grants from Clarus Therapeutics outside the submitted work. Dr. Diwan has served as a consultant for the interpretation of echocardiograms for clinical trials for Clario (previously ERT) and has received nonfinancial support from Dewpoint Therapeutics outside the submitted work. Dr. Dandana has disclosed no relevant financial relationships.

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

Among men who have not been vaccinated against COVID-19, having low levels of testosterone may increase the risk of hospitalization from the disease – but hormone therapy appears to reduce the likelihood of severe COVID, researchers have found.

Low testosterone has long been linked to multiple chronic conditions, including obesity, heart disease, and type 2 diabetes, as well as acute conditions, such as heart attack and stroke. A study published earlier in the pandemic suggested that suppressing the sex hormone might protect against COVID-19. The new study, published in JAMA Network Open, is among the first to suggest a link between low testosterone and the risk for severe COVID.

Researchers at Washington University in St. Louis evaluated data from 723 unvaccinated men who had been infected with SARS-CoV-2. Of those, 116 had been diagnosed with hypogonadism, and 180 were receiving testosterone supplementation.

The study found that men whose testosterone levels were less than 200 ng/dL were 2.4 times more likely to experience a severe case of COVID-19 that required hospitalization than were those with normal levels of the hormone. The study accounted for the fact that participants with low testosterone were also more likely to have comorbidities such as diabetes and obesity.

Paresh Dandona, MD, PhD, distinguished professor of medicine and endocrinology at the State University of New York at Buffalo, called the findings “very exciting” and “fundamental.”

“In the world of hypogonadism, this is the first to show that low testosterone makes you vulnerable” to COVID, added Dr. Dandona, who was not involved with the research.

Men who were receiving hormone replacement therapy were at lower risk of hospitalization, compared with those who were not receiving treatment, the study found.

“Testosterone therapy seemed to negate the harmful effects of COVID,” said Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University and lead author of the study.

Approximately 50% more men have died from confirmed COVID-19 than women since the start of the pandemic, according to the Sex, Gender and COVID-19 Project. Previous findings suggesting that sex may be a risk factor for death from COVID prompted researchers to consider whether hormones may play a role in the increased risk among men and whether treatments that suppress androgen levels could cut hospitalizations, but researchers consistently found that androgen suppression was not effective.

“There are other reasons women might be doing better – they may have followed public health guidelines a lot better,” according to Abhinav Diwan, MD, professor of medicine at Washington University in St. Louis, who helped conduct the new study. “It may be chromosomal and not necessarily just hormonal. The differences between men and women go beyond one factor.”

According to the researchers, the findings do not suggest that hormone therapy be used as a preventive measure against COVID.

“We don’t want patients to get excited and start to ask their doctors for testosterone,” Dr. Dhindsa said.

However, viewing low testosterone as a risk factor for COVID could be considered a shift in thinking for some clinicians, according to Dr. Dandana.

“All obese and all [men with] type 2 diabetes should be tested for testosterone, which is the practice in my clinic right now, even if they have no symptoms,” Dr. Dandana said. “Certainly, those with symptoms [of low testosterone] but no diagnosis, they should be tested, too.”

Participants in the study were infected with SARS-CoV-2 early in 2020, before vaccines were available. The researchers did not assess whether the rate of hospitalizations among participants with low testosterone would be different had they been vaccinated.

“Whatever benefits we saw with testosterone might be minor compared to getting the vaccine,” Dr. Dhindsa said.

Dr. Diwan agreed. “COVID hospitalization continues to be a problem, the strains are evolving, and new vaccines are coming in,” he said. “The bottom line is to get vaccinated.”

Dr. Dhindsa has received personal fees from Bayer and Acerus Pharmaceuticals and grants from Clarus Therapeutics outside the submitted work. Dr. Diwan has served as a consultant for the interpretation of echocardiograms for clinical trials for Clario (previously ERT) and has received nonfinancial support from Dewpoint Therapeutics outside the submitted work. Dr. Dandana has disclosed no relevant financial relationships.

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

Among men who have not been vaccinated against COVID-19, having low levels of testosterone may increase the risk of hospitalization from the disease – but hormone therapy appears to reduce the likelihood of severe COVID, researchers have found.

Low testosterone has long been linked to multiple chronic conditions, including obesity, heart disease, and type 2 diabetes, as well as acute conditions, such as heart attack and stroke. A study published earlier in the pandemic suggested that suppressing the sex hormone might protect against COVID-19. The new study, published in JAMA Network Open, is among the first to suggest a link between low testosterone and the risk for severe COVID.

Researchers at Washington University in St. Louis evaluated data from 723 unvaccinated men who had been infected with SARS-CoV-2. Of those, 116 had been diagnosed with hypogonadism, and 180 were receiving testosterone supplementation.

The study found that men whose testosterone levels were less than 200 ng/dL were 2.4 times more likely to experience a severe case of COVID-19 that required hospitalization than were those with normal levels of the hormone. The study accounted for the fact that participants with low testosterone were also more likely to have comorbidities such as diabetes and obesity.

Paresh Dandona, MD, PhD, distinguished professor of medicine and endocrinology at the State University of New York at Buffalo, called the findings “very exciting” and “fundamental.”

“In the world of hypogonadism, this is the first to show that low testosterone makes you vulnerable” to COVID, added Dr. Dandona, who was not involved with the research.

Men who were receiving hormone replacement therapy were at lower risk of hospitalization, compared with those who were not receiving treatment, the study found.

“Testosterone therapy seemed to negate the harmful effects of COVID,” said Sandeep Dhindsa, MD, an endocrinologist at Saint Louis University and lead author of the study.

Approximately 50% more men have died from confirmed COVID-19 than women since the start of the pandemic, according to the Sex, Gender and COVID-19 Project. Previous findings suggesting that sex may be a risk factor for death from COVID prompted researchers to consider whether hormones may play a role in the increased risk among men and whether treatments that suppress androgen levels could cut hospitalizations, but researchers consistently found that androgen suppression was not effective.

“There are other reasons women might be doing better – they may have followed public health guidelines a lot better,” according to Abhinav Diwan, MD, professor of medicine at Washington University in St. Louis, who helped conduct the new study. “It may be chromosomal and not necessarily just hormonal. The differences between men and women go beyond one factor.”

According to the researchers, the findings do not suggest that hormone therapy be used as a preventive measure against COVID.

“We don’t want patients to get excited and start to ask their doctors for testosterone,” Dr. Dhindsa said.

However, viewing low testosterone as a risk factor for COVID could be considered a shift in thinking for some clinicians, according to Dr. Dandana.

“All obese and all [men with] type 2 diabetes should be tested for testosterone, which is the practice in my clinic right now, even if they have no symptoms,” Dr. Dandana said. “Certainly, those with symptoms [of low testosterone] but no diagnosis, they should be tested, too.”

Participants in the study were infected with SARS-CoV-2 early in 2020, before vaccines were available. The researchers did not assess whether the rate of hospitalizations among participants with low testosterone would be different had they been vaccinated.

“Whatever benefits we saw with testosterone might be minor compared to getting the vaccine,” Dr. Dhindsa said.

Dr. Diwan agreed. “COVID hospitalization continues to be a problem, the strains are evolving, and new vaccines are coming in,” he said. “The bottom line is to get vaccinated.”

Dr. Dhindsa has received personal fees from Bayer and Acerus Pharmaceuticals and grants from Clarus Therapeutics outside the submitted work. Dr. Diwan has served as a consultant for the interpretation of echocardiograms for clinical trials for Clario (previously ERT) and has received nonfinancial support from Dewpoint Therapeutics outside the submitted work. Dr. Dandana has disclosed no relevant financial relationships.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Almost half the people who were hospitalized with COVID-19 last spring had been fully vaccinated and received a third dose or booster shot, the Centers for Disease Control and Prevention says.

Unvaccinated adults were 3.4 times more likely to be hospitalized with COVID than those who were vaccinated, the CDC said.

The CDC report considered hospitalization numbers from March 20 to May 31, when the omicron subvariant BA.2 was the dominant strain. Researchers found 39.1% of patients had received a primary vaccination series and at least one booster or additional dose; 5% were fully vaccinated with two boosters.

“Adults should stay up to date with COVID-19 vaccination, including booster doses,” the CDC said. “Multiple nonpharmaceutical and medical prevention measures should be used to protect persons at high risk for severe SARS-CoV-2, regardless of vaccination status.”

Older adults and people with underlying medical conditions who become infected with the coronavirus are more likely to be hospitalized.

The study also found that hospitalization rates among people over 65 increased threefold over the study period. Rates among people under 65 rose 1.7 times.

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

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Women who are pregnant or breastfeeding showed no long-term adverse reactions after a third or booster dose of COVID-19 vaccine, according to a study of more than 17,000 individuals.

Doctors and health professionals continue to recommend COVID-19 vaccine boosters or third doses for adolescents and adults more than 5 months after their initial vaccinations with the Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273 primary vaccine series or more than 2 months after receiving the Janssen JNJ-78436735 vaccine, Alisa Kachikis, MD, of the University of Washington, Seattle, and colleagues wrote in JAMA Network Open.

Although multiple studies have shown that the COVID-19 primary series is safe and well tolerated in pregnant and lactating women, information on the safety and tolerability of boosters are lacking, the researchers noted.

“COVID-19 will be with us for a while, and it is important to continue to provide data on COVID-19 vaccines in these groups, particularly because there still are many questions about the vaccine, and because pregnant individuals have been, understandably, more hesitant to receive COVID-19 vaccines,” Dr. Kachikis said in an interview. “The findings of this study that COVID-19 booster doses are well tolerated among pregnant and lactating individuals are especially pertinent with the new COVID-19 boosters available this fall.”

In the new study, the researchers reviewed data from 17,014 participants who were part of an ongoing online prospective study of COVID-19 vaccines in pregnant and lactating individuals. Data were collected between October 2021 and April 2022 through an online survey.

The study population included 2,009 participants (11.8%) who were pregnant at the time of their booster or third dose, 10,279 (60.4%) who were lactating, and 4,726 (27.8%) who were neither pregnant nor lactating. The mean age of the participants was 33.3 years; 92.1% self-identified as White, 94.5% self-identified as non-Hispanic, and 99.7% self-identified as female.

The receipt of a booster was similar across trimesters; 26.4%, 36.5%, and 37.1% of participants received boosters or third doses in the first, second, and third trimester, respectively. The primary outcome was self-reported vaccine reactions within 24 hours of the dose.

Overall, 82.8% of the respondents reported a reaction at the site of the injection, such as redness, pain, or swelling, and 67.9% reported at least one systemic symptom, such as aches and pains, headache, chills, or fever. The most frequently reported symptoms across all groups were injection-site pain (82.2%) and fatigue (54.4%).

The pregnant women were significantly more likely than nonpregnant or nonlactating individuals to report any local reaction at the injection site (adjusted odds ratio, 1.2; P = .01), but less likely to report any systemic reaction (aOR, 0.7; P < .001).

The majority (97.6%) of the pregnant respondents and 96.0% of those lactating reported no obstetric or lactation concerns after vaccination.

Overall, a majority of the respondents reported that recommendations from public health authorities were helpful in their decision to receive a COVID-19 booster or third dose (90.0% of pregnant respondents, 89.9% of lactating respondents, and 88.1% of those neither pregnant nor lactating).

Although vaccine uptake in the current study population was high (91.1% overall and 95.0% of those pregnant), “the importance of the health care professional’s recommendation is pertinent given the ongoing increased vaccine hesitancy among pregnant individuals in the context of the COVID-19 vaccine,” the researchers emphasized.

The study findings were limited by several factors including the reliance on self-reports and a convenience sample composed mainly of health care workers because of their vaccine eligibility at the time the study started, which limits generalizability, the researchers noted. Analyses on the pregnancy outcomes of those who were pregnant when vaccinated are in progress.

The results were strengthened by the large study population that included participants from all 50 states and several territories, and ability to compare results between pregnant and lactating individuals with those who were neither pregnant nor lactating, but were of childbearing age, they said.

The results support the safety of COVID-19 boosters for pregnant and breastfeeding individuals, and these data are important to inform discussions between patients and clinicians to boost vaccine uptake and acceptance in this population, they concluded.

“Our earlier data analysis showed that pregnant and lactating individuals did very well with the initial COVID-19 vaccine series, so it was not very surprising that they also did well with COVID-19 booster or third doses,” Dr. Kachikis said in an interview.

There are two takeaway messages for clinicians, she said: “First, pregnant and lactating individuals tolerated the COVID-19 booster well. The second is that clinicians are very important when it comes to vaccine acceptance.”

“In our study, we found that, while pregnant participants were more likely to report that they were hesitant to receive the booster, they also were more likely to have discussed the COVID-19 booster with their health care provider, and to have received a recommendation to receive the booster. So, spending a little bit of extra time with patients discussing COVID-19 boosters and recommending them can make a significant difference,” she said.

The message of the study is highly reassuring for pregnant and lactating individuals, Dr. Kachikis added. “Most of the participants reported that they had fewer symptoms with the COVID-19 booster compared to the primary vaccine series, which is good news, especially since a new COVID-19 booster is being recommended for the fall.”
 

Reassuring findings for doctors and patients

The current study is especially timely, as updated COVID-19 boosters have now been recommended for most individuals by the Centers for Disease Control and Prevention, Martina L. Badell, MD, a maternal-fetal medicine specialist at Emory University, Atlanta, said in an interview.

The findings support previous studies on the tolerability of COVID-19 vaccinations in pregnant and lactating persons, said Dr. Badell, who was not involved in the study.

The reassuring message for clinicians is that COVID-19 booster vaccinations are similarly well tolerated in pregnancy and lactation as they are in nonpregnant individuals, said Dr. Badell. “Given the risks of COVID infections in pregnancy and neonates, reassuring data on the tolerability and safety of vaccination in this population is very important.” Also, the researchers found that all three cohorts reported that recommendations from public or medical health authorities helped them make a decision about vaccination; “thus the more data to support these recommendations, the better,” she emphasized.

If you are pregnant or breastfeeding, the message from the study is that COVID-19 booster vaccinations are similarly well tolerated by those who are pregnant or breastfeeding and those who are not, said Dr. Badell.

“This study provides additional support for the strong recommendation to encourage not only COVID-19 vaccination in pregnancy and lactation, but booster vaccinations specifically,” and pregnant and breastfeeding individuals should not be excluded from the new CDC recommendations for COVID-19 boosters, she said.
 

Future research suggestions

Next steps for research include evaluating the obstetrical and neonatal outcomes in pregnancy and lactation following COVID- 19 boosters, Dr. Badell added.

Dr. Kachikis suggested studies try to answer the remaining questions about COVID-19 vaccines and the immunity of pregnant and lactating persons, particularly since they were excluded from the early clinical trials in 2020.

The study was supported by the National Institute of Allergy and Infectious Diseases, a Women’s Reproductive Health Research Award, and the National Center for Advancing Translational Sciences of the National Institutes of Health. \Dr. Kachikis disclosed serving as a research consultant for Pfizer and GlaxoSmithKline and as an unpaid consultant for GlaxoSmithKline unrelated to the current study, as well as grant support from Merck and Pfizer unrelated to the current study. Dr. Badell had no financial conflicts to disclose.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.

Unvaccinated people may be 10 times more likely than fully vaccinated people to be hospitalized for the Omicron variant of COVID-19, suggests a large study conducted by the U.S. Centers for Disease Control and Prevention.

The data, which included almost 200,000 COVID-19–associated hospitalizations across 13 states, also showed that vaccinated, hospitalized patients were more often older and already dealing with other health conditions, compared with unvaccinated, hospitalized patients, reported lead author Fiona P. Havers, MD, of the CDC, Atlanta.

“Unlike previously published reports and web pages … this study reports hospitalization rates by vaccination status and clinical and demographic characteristics of hospitalized patients, beginning with the period when vaccines first became available, and includes comparisons of unvaccinated persons, persons vaccinated with a primary series without a booster dose, and those vaccinated with a primary series and at least 1 booster dose,” the investigators wrote in JAMA Internal Medicine.

In total, the investigators reviewed 192,509 hospitalizations involving patients 18 years and older. The study period spanned from Jan. 1, 2021, to April 30, 2022. Data were reported month by month, showing that the relative monthly hospitalization rate peaked in May 2021, when it was 17.7 times higher for unvaccinated versus vaccinated individuals (with or without a booster).

To account for differences in clinical course between Delta and Omicron, the investigators also analyzed data sorted into two time periods: July-December 2021 (Delta predominant) and January-April 2022 (Omicron BA.1 predominant). These analyses revealed the greater hospitalization risk presented by Delta. Specifically, unvaccinated people were 12.2 times more likely to be hospitalized for Delta than vaccinated people, with or without a booster, versus 6.8 times for Omicron BA.1.

Study shows power of the booster

A closer look at the Omicron BA.1 data showed the power of a booster dose. From January to April 2022, individuals who were fully vaccinated with a booster dose were 10.5 times less likely than unvaccinated individuals to be hospitalized for Omicron BA.1. Plus, boosted people were 2.5 times less likely to be hospitalized for Omicron BA.1 than people who got vaccinated but skipped the booster.

“The high hospitalization rates in unvaccinated compared with vaccinated persons with and without a booster dose underscores the importance of COVID-19 vaccinations in preventing hospitalizations and suggests that increasing vaccination coverage, including booster dose coverage, can prevent hospitalizations, serious illness, and death,” the investigators wrote.

The study also revealed that vaccinated hospitalized patients were significantly older, on average, than unvaccinated hospitalized patients (median, 70 vs. 58 years; P < .001). They were also significantly more likely to have three or more underlying medical conditions (77.8% vs. 51.6%; P < .001)

“A greater proportion of hospitalized cases among vaccinated persons occurred in individuals with medical fragility who were older, more likely to reside in long-term care facilities, and have three or more underlying medical conditions, including immunosuppressive conditions,” the investigators wrote.

New variants outpacing data, vaccines remain essential

While data from April 2022 alone showed a 3.5-fold higher rate of hospitalization among unvaccinated versus vaccinated individuals with or without a booster, newer data suggest that emerging strains of Omicron are putting more people in the hospital.

A recent report by the CDC showed weekly hospitalization rates climbing from March 20 to May 31, 2022, which coincided with predominance of the newer Omicron BA.2 variant. While unvaccinated people were still around 3.5 times more likely to be hospitalized than vaccinated people, overall hospitalization rates jumped 3-fold for people 65 years and older, and 1.7-fold for adults younger than 65. Adding further complexity to this constantly evolving situation is that Omicron BA.2 has since been joined by the BA.4 and BA.5 lineages, for which vaccines are now available.

In the paper published in JAMA Internal Medicine, the CDC report, and in a comment for this article, the CDC offered the same take-home message: Get vaccinated.

“These findings reinforce previous research illustrating how vaccination provides protection from hospitalization due to COVID-19,” a CDC spokesperson said. “COVID-19 vaccines are proven to help prevent serious COVID-19 illness, and everyone ages 6 months and older should stay up to date with COVID-19 vaccines.”

The study published in JAMA Internal Medicine was supported by the CDC. The investigators disclosed additional relationships with Sanofi, GSK, MedImmune, and others.