Infectious Disease Practitioner

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Most SARS-CoV-2 virus strains feature a specific mutation that makes them more transmissible, to the point that these strains now predominate globally, new evidence shows.

In contrast to a greater variety of strains early in the pandemic, now 99.9% of circulating SARS-CoV-2 strains in the study feature the D614G mutation on the spike protein. In addition, people infected with a D614G strain have higher nasopharynx viral loads at diagnosis.

It’s not all bad news. This single-point mutation was not associated with worse clinical COVID-19 severity. Also, the mutation isn’t expected to interfere with the efficacy any of the antibody cocktails, small molecule therapies or vaccines in development.

Furthermore, “as bad as SARS-CoV-2 is, we may have dodged a bullet in terms of how quickly it mutates,” study author Ilya Finkelstein, PhD, said in an interview. This virus mutates much slower than HIV, for example, giving researchers a greater chance to stay one step ahead, he said.

The study was published online Oct. 30 in the journal mBio.
 

Molecular sleuthing

The research was possible because colleagues at the Houston Methodist Hospital system sequenced the genome of 5085 SARS-CoV-2 strains early in the outbreak and during a second wave of infection over the summer, Dr. Finkelstein said.

The unique data source also includes information from plasma, convalescent plasma, and patient outcomes. Studying a large and diverse population in a major metropolitan area like Houston helps create a “molecular fingerprint” for the virus that will continue to be very useful, said Dr. Finkelstein, a researcher and director of the Finkelstein Lab at the University of Texas, Austin.

D614G was the most common genetic substitution the researchers found, appearing in 82% of SARS-CoV-2 strains during the first wave from March 5 to May 11. The proportion with this mutation jumped to 99.9% by the second wave, defined as occurring between May 12 and July 7 in the study.

The jump in mutation frequency “occurred very rapidly, in a matter of just a few months,” the researchers noted.

The presence of the mutation during the first wave was independently associated with mechanical ventilation days, overall length of stay, and ICU length of stay. However, it was not associated with any significant differences in patient outcomes.

The D614G mutation is now so common worldwide that these viruses are considered reference strains. Researchers believe D614G predominates because it increases the spike protein’s ability to open cells for the virus to enter.

Despite the large number of virus strains evaluated, the samples only represent about 10% of COVID-19 cases in Houston during the study, a potential limitation. Also, some collected samples could not be used for high-quality genome analysis because of limited virus nucleic acid.

Also, it remains unclear if host-virus immune interactions play a significant role. However, the researchers noted in the paper that “available data suggest that, in the aggregate, host genetics does not play an overwhelming role in determining outcome in the great majority of adult patients, once virus infection is established.”
 

Surveillance ongoing

“The findings will help us to understand the origin, composition, and trajectory of future infection waves and the potential effect of the host immune response and therapeutic maneuvers on SARS-CoV-2 evolution,” the researchers added.

Going forward, the ongoing molecular surveillance of SARS-CoV-2 “may provide critical insights into the origin of the new infection spikes and waves that are occurring as public health constraints are further relaxed, schools and colleges reopen, holidays occur, commercial air travel increases and individuals change their behavior because of COVID-19 ‘fatigue,’ ” the researchers noted.

They added that the genome data will also be useful in assessing ongoing molecular evolution in spike and other proteins “as baseline herd immunity is generated, either by natural exposure to SARS-CoV-2 or by vaccination.”
 

Further validation warranted

“The study is very interesting and well performed,” Noam Shomron, PhD, a member of the faculty of medicine at Tel Aviv University, said in an interview.

Analyzing the “SARS-CoV-2 molecular evolution in a specific region in the USA … could be viewed as a microcosm of what occurs in other large cities in the USA,” he said.

However, “before jumping to conclusions, this should be further validated,” added Dr. Shomron, who authored a study suggesting differences in genetic alleles could partially explain variations across countries in the infection rates, severity, and mortality associated with SARS-CoV-2.

“We know that many other features and contributors might affect the results – even social constraints could generate a bias in the observations,” he said. 

Dr. Finkelstein and Dr. Shomron disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

In a large international study of patients admitted to the ICU with COVID-19, the likelihood of having severe pneumonia (i.e., needing invasive mechanical ventilation) increased stepwise with increasing body mass index (BMI) – independent of diabetes, hypertension, dyslipidemia, or current smoking.

The main finding was a linear correlation between BMI and need for invasive mechanical ventilation, after adjustment for center, age, sex, and other prespecified metabolic risk factors.

Risk was “highest for older people and males, but the next most important risk factor to developing severe pneumonia if infected [was] obesity,” said François Pattou, MD, Centre Hospitalier Universitaire de Lille (France), who presented the findings at the ObesityWeek 2020 virtual meeting. The results were also recently published in a preprint article in The Lancet.

Dr. Pattou and colleagues first reported back in April that obesity is one of the biggest risk factors for severe COVID-19 infection, especially in younger patients. Many further reports linked the two, and the French researchers then set out to conduct the current large, international, multicenter cohort study.

“The high number of patients included here [allowed us] to disentangle the role of various metabolic cofactors and to show that obesity, not diabetes or hypertension, was the main determinant of severe pneumonia [after age and gender],” Dr. Pattou said in an interview.

And the impact of obesity was most pronounced in women younger than 50 years.
 

Patients with severe obesity must protect themselves

Of interest, the study also found an “obesity paradox” for mortality after admission to the ICU.

Specifically, compared with leaner patients (BMI < 25 kg/m²), those with severe obesity (obesity class III, BMI ≥ 40) had an increased risk of dying within 28 days of admission to ICU. But patients with overweight to moderate obesity (BMI 25-39.9) had a lower risk of this outcome.

“The second original finding of our study,” Dr. Pattou continued, was the “nonlinear relation observed between BMI and all-cause mortality rate in ICU patients.”

Matteo Rottoli, MD, PhD, author of a related study reported by in July, said the new trial “confirms the findings of our study, which are that obesity is an independent risk factor for intensive care admission and death.”

Dr. Rottoli, from Alma Mater Studiorum, University of Bologna, Italy, and colleagues found that in their population of patients with COVID-19, a BMI > 35 was associated with a greater risk of death.

The takeaway message from the research is that “obesity should be considered one of the most important parameters to identify the population at risk” of getting COVID-19 who need to take extra precautions such as social distancing, Dr. Rottoli stressed.

Dr. Pattou agrees, particularly when it comes to severe obesity.

Intensive care physicians have learned a lot in the past months about COVID-19 pneumonia and how to address it (such as not precipitating intubation, using corticosteroids), he explained.

“Importantly, the general population has also learned a lot, and we can hope that patients with obesity, especially those with severe obesity, will take extra measures to protect themselves, resulting in a decrease of the incidence of severe pneumonia in young and severely obese patients,” he added.
 

Untangling BMI from other metabolic risk factors

Dr. Pattou said that, from Dec. 16, 2019, to Nov. 1, 2020, more than 45 million people worldwide tested positive for COVID-19 and more than 1.2 million people died from it.

Multiple studies have reported that, among people with COVID-19, those with obesity are at higher risk of hospitalization, ICU admission, invasive ventilation, and death, but it had not been clear if BMI was an independent risk factor.

Dr. Pattou and colleagues aimed to examine the relationship between BMI and COVID-19 pneumonia severity, defined by the need for mechanical ventilation (primary outcome), as well as 28-day all-cause mortality (secondary outcome) among patients admitted to the ICU.

They also sought to disentangle the effect of BMI from other metabolic risk factors (diabetes, hypertension, dyslipidemia, and current smoking) and examine the influence of age and sex on outcomes.

They performed a retrospective analysis of 1,461 patients with confirmed COVID-19 (positive reverse polymerase chain reaction test using a nasal or pharyngeal swab specimen) who were admitted to the ICU at 21 centers from Feb. 19 to May 11, 2020.

Participating centers were in France (13), Italy (3), the United States (1 in New York and 1 in Providence, R.I.), Israel (1), Belgium (1), and Spain (1).

Close to three-quarters of patients were men (73%), which is similar to multiple other studies, Dr. Pattou said. Patients were a mean age of 64 years and had a mean BMI of 28.1.

Half of patients had hypertension (52%), 29% had diabetes, 29% had hyperlipidemia, and 6.5% were current smokers.

Close to three-quarters (74%) required invasive mechanical ventilation, and 36% died within 28 days of ICU admission.

Each 5-kg/m² increase in BMI was associated with a 27% increased risk of mechanical ventilation in the overall cohort and a 65% increased risk of this outcome among women younger than 50 years, after adjustment for other risk factors.

Male sex and each 10-year increase in age were associated with an 82% and a 17% increased risk of ventilation, respectively, but hypertension, diabetes, hyperlipidemia, and current smoking were not associated with a greater risk. After adjustment for center, age, sex, and prespecified metabolic risk factors, obesity class III (BMI ≥ 40) was associated with a 68% increase in mortality, compared with the risk seen in lean patients.

The findings were similar across different centers.

“To our knowledge, this study represents the first international collaborative effort to explore the association of BMI with the outcomes of pneumonia among COVID-19 patients admitted to ICU,” said the investigators.

They conclude that “available evidence should foster more focused and effective interventions in COVID-19 patients with the highest risk of severe pneumonia, in order to reduce future strain on intensive care resources worldwide, and inform physio-pathological research to elucidate the mechanism of severe lung damage in COVID-19.”

The study did not receive specific funding. The authors have reported no relevant financial relationships.
 

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The first study to suggest benefit from low-dose radiotherapy for severe COVID-19–induced pneumonia involved only 20 patients, but the results were so promising that two larger randomized trials are now underway.

“RESCUE-119 was a trial based on the hypothesis that low-dose radiation therapy may help eliminate the stormy cytokine release and unchecked edema in hospitalized COVID-19 patients,” said Mohammed Khan, MD, PhD, Winship Cancer Institute of Emory University, Atlanta.

“We found patients had a quicker improvement in their time to clinical recovery with low-dose radiation therapy, compared to controls, and this was significant even in this small cohort of patients,” he said.

Dr. Khan was speaking at a special press briefing held during the virtual American Society for Radiation Oncology Annual Meeting 2020.

A total of 20 patients were involved in the trial. Ten patients were treated with low-dose radiotherapy; 10 others, who served as control patients, were treated with the best supportive care and COVID-directed therapies. The control patients were matched for age and comorbidities. All these patients were hospitalized and were oxygen dependent, Dr. Khan noted. In addition, for all patients, serial x-rays demonstrated consolidation and damage in the lung.

The intervention consisted of whole-lung low-dose radiotherapy delivered at a dose of 1.5 Gy.

The first five patients were assessed at an interim endpoint of 7 days to confirm the safety of the procedure. Subsequently, a total of 10 patients were treated with radiotherapy and were followed to day 28.

The main study endpoints were time to clinical recovery, determined on the basis of the patient’s being taken off oxygen, and improvement, evidenced on either serial x-rays or by inflammatory biomarkers.

The median time to clinical recovery was almost three times faster for the patients who received low-dose radiotherapy, at a median of 3 days; for control patients, the median was 12 days (P = .048).

“We also saw a trend toward getting patients out of hospital sooner,” Dr. Khan added. The mean time to hospital discharge was 12 days for the patients who received low-dose radiotherapy, compared with 20 days for control patients (P = .19).

Only one patient required intubation after receiving low-dose radiotherapy, whereas 4 of 10 control patients required some sort of intubation (P = .12), he noted.

Investigators also saw improvements on serial x-rays in 9 of 10 patients treated with low-dose radiotherapy, compared with only 4 patients in the control group. There was also a significant improvement in delirium among the low-dose radiotherapy group compared with control patients (P < .01). Before receiving low-dose radiotherapy, C-reactive protein levels increased by 22% per day. After receiving the 1.5-Gy radiation treatment, there was a sharp reduction in C-reactive protein levels (P < .01) as well as in lactate dehydrogenase levels (P = .03).

Overall survival, however, did not differ between the two treatment groups; 90% of both groups were alive at day 28.

“By focally dampening cytokine hyperactivation, [low-dose radiotherapy] may improve COVID-19 outcomes through immunomodulation,” Dr. Khan explained.
 

VENTED and PRE-VENT trials

These results from the small RESCUE-119 trial led to the launch of two larger phase 2 trials, the VENTED and the PRE-VENT trials, noted Arnab Chakravarti, MD, professor and chair of radiation oncology, the Ohio State University Comprehensive Cancer Center, Columbus.

To be enrolled in the VENTED trial, patients must have received mechanical ventilation. They will receive at least one dose of ultra-low-dose bilateral whole-lung radiotherapy, with the option of receiving a second dose. The primary objective is 30-day mortality rate.

“The hypothesis is that low-dose thoracic radiation will decrease inflammation and improve outcomes for these intubated COVID-19 patients,” Dr. Chakravarti explained.

The PRE-VENT trial will explore low-dose thoracic radiotherapy for hospitalized patients with severe respiratory compromise who have not yet been intubated. Two doses of low-dose radiotherapy will be tested and compared. The primary study objective is to determine which of the two doses appears to be the most efficacious, Dr. Chakravarti noted.

“The ultimate question to which we remain agnostic is whether the potential benefits of low-dose radiation therapy outweigh the risks,” he said.

Low-dose radiotherapy is readily available in most countries, unlike the newly developed COVID-19 drugs, which are only available in the developed world, he noted. “This creates a bit more economic equity in terms of COVID-19 treatment.”

In addition, it may offer a therapeutic option that could be useful in the future, “as low-dose radiation therapy does not discriminate against various viruses that may cause another pandemic,” he commented. It could offer “a stopgap measure where we don’t have to shut down society completely, which, as we have all witnessed, can cause tremendous financial and social unrest.”
 

Reasonable question

Whether or not radiotherapy has value for the short-term management of severe pulmonary inflammation caused by COVID-19 is a reasonable question to evaluate in clinical trials, commented discussant Ramesh Rengan, MD, PhD, professor and chair, department of radiation oncology, University of Washington, Seattle.

He noted that inflammatory cells are highly sensitive to radiation, and low-dose radiotherapy has been used effectively in other inflammatory conditions, such as arthritis. Indeed, before the discovery of antibiotics, low-dose radiation was used with reasonable efficacy to treat pneumonia.

“The pneumonia associated with this viral infection is a bit unique in that what happens is the infection triggers an inflammatory cascade – the so-called cytokine storm – that essentially overwhelms the lungs, thereby leading, unfortunately, to mortality,” Dr. Rengan noted. “So a big focus of our energy is how to stop this inflammatory cascade from occurring.”

Corticosteroids are currently the only therapeutic intervention that has shown any mortality benefit in COVID-19, he pointed out.

The question now being asked is: “Can we suppress inflammation specifically within the lung?” Dr. Rengan continued. The main problem with radiotherapy is that it has different effects on various tissues, both immediately and over the long term.

“The immediate benefit that we will likely see from these studies is the immediate sterilization of inflammatory cells,” he said. However, injury to normal lung tissue from low-dose radiotherapy could lead to inflammation weeks or months later, and this could contribute to the disease burden and increase the risk of dying.

Dr. Rengan also noted that there are some very real practical concerns about offering radiotherapy to COVID-19 patients, including potential COVID-19 transmission to vulnerable cancer patients.

Nevertheless, Dr. Rengan said the results to date are very important and that ongoing trials will provide important new information about the long-term impact of this particular treatment in high-risk patients.

“This is a race to the bottom – we are trying to find the lowest possible dose of radiation therapy that we can deliver to sterilize these inflammatory cells without creating any harm to the surrounding tissue,” he said.

“It also brings radiation oncologists into the fight against this deadly disease,” he added.

Dr. Rengan has received honoraria from Novocur and has served as a consultant to AstraZeneca.

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

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

The age of antiretroviral therapy (ART) for HIV is in its third decade, and many of the patients who live in areas of the world fortunate enough to have had early access to therapy have now lived for several decades with complications of HIV and viral suppressive therapy.

But while the life-expectancy of persons with HIV has approached that of noninfected persons over the last 20 years, the higher burden of comorbidities for aging patients with HIV has remained largely the same, according to an epidemiologist who specializes in HIV/AIDS research and aging.

“The pathways from HIV and its treatments to comorbidities are very long and winding, spanning a life course. Social determinants of health and individual risk factors also play an important role, and must be considered,” said Keri N. Althoff, PhD, MPH, of Johns Hopkins University, Baltimore.

Dr. Althoff discussed long-term complications of HIV and its treatment in a virtual symposium during an annual scientific meeting on infectious diseases.

“Many urban HIV providers have an increased proportion of patients who are older long-term survivors of the epidemic. Many, but not all of the comorbidities (including cardiovascular, neurocognitive, renal, and malignancies) have been associated with age, long-term HIV infection, especially uncontrolled HIV infection, and low CD4 nadirs,” commented Harry Lampiris, MD, professor of clinical medicine at the University of California, San Francisco.

“An increasing number of patients are experiencing geriatric syndromes (especially problems with mobility, cognitive decline, food insecurity, polypharmacy, and social isolation) at younger ages than HIV-negative populations,” he added.

Dr. Lampiris, who moderated the session where Dr. Althoff presented her findings, commented on it in an interview, but was not involved in her research.
 

Pathways to comorbidity

The three primary pathways to comorbidities in people with HIV infections are as follows, according to Dr. Athloff:

• The virus itself, with its associated inflammation, immunosuppression, immune activation, and AIDS.
• HIV therapies, beginning with the notoriously toxic dideoxynucleoside analogues or “d-drugs,” and following with subsequent generations of newer, less toxic agents.
• Individual risk factors, including smoking, stress, diet, exercise, and environment.

Cardiovascular and renal complications

Persons with HIV have an approximately twofold higher risk for major adverse cardiovascular events (myocardial infarction, stroke) compared with persons without HIV. Conditions contributing to cardiovascular disease including hypertension, diabetes, and hyperlipidemia are also significantly higher among persons with HIV, Dr. Althoff said.

Hypertension among persons with HIV from the ages 60-69 years is especially high for Black men and to a lesser degree non-Black men, compared with either White or Black women, she noted.

Pathways to renal disease in persons with HIV include diabetes and hypertension, as well as therapies to treat them, hepatitis B and C coinfection, HIV-associated nephropathy, and immune complex kidney disease, as well as chronic kidney disease resulting from acute kidney injury related to therapy.

“Cardiovascular disease and kidney disease are excellent examples of why the life-course perspective is essential when caring for people with HIV. For those diagnosed with HIV at younger ages, there are points of intervention along the decades-long path, and the timing and implementation of the most effective intervention may preserve comorbidity-free years,” Dr. Althoff said.

Prevention and screening interventions to lower risk for future heart- and kidney-related comorbidities include smoking cessation and lifestyle optimization (diet, exercise, mental health), as well as lipid-lowering medications to lower risk for cardiovascular events.
 

Liver comorbidities

“Primary drivers of liver disease are social determinants of health and individual lifestyle risk factors that share the same pathways as HIV, resulting in this increased burden of liver disease in people with HIV,” she said.

Risk factors include alcoholic liver disease, nonalcoholic fatty liver disease, hepatitis B and C coinfection, drug use, autoimmune disease, and aging. These risk factors contribute to oxidative stress, mitochondrial injury, lipotoxicity, cytotoxicity, and other mechanisms that can lead to fibrosis, cirrhosis, hepatocellular carcinoma, and end-stage liver disease.

“I want to be sure to acknowledge the importance of liver disease as a comorbidity among people with HIV. Liver disease accounts for nearly 20% of mortality in persons with HIV,” she said.
 

Neurocognitive problems

HIV has been linked to neurocognitive decline since the beginning of the epidemic, Dr. Althoff noted. The term HIV-associated neurocognitive disorders encompasses the broad spectrum of cognitive effects of HIV, from asymptomatic illness to AIDS-related dementia. Estimates of cognitive impairment in people with HIV range from 14% to 64% across various study populations, but diagnosing and treating it in the community can be challenging.

“Routine monitoring of cognition is often just out of reach in the clinical setting, due to the time it takes to use validated tools. We need a deeper toolbox of quick and validated tools calibrated to people with HIV in order to accurately monitor cognition,” she said.

She noted that the average age of onset of Alzheimer’s disease in the general population is 80 years, and that relatively few people with HIV infection have reached that age.

“But before the population age distribution shifts to the older ages, we can do more to monitor cognition in people with HIV,” she added.

In addition to HIV, factors that can contribute to worse neurocognitive outcomes include major depressive disorder, occurring in and estimated 20%-40% of adults with HIV versus 8% of the U.S. population, generalized anxiety disorder (10%-25% vs. 3%), bipolar disorder (3%-9% vs. 3%), schizophrenia (4%-15% vs. 1%), and posttraumatic stress disorder (10%-30% vs. 8%).

Substance use and polypharmacy, common among adults with HIV, can also contribute to cognitive decline, she said.
 

Decreased mobility

The Multicenter AIDS Cohort Study (MACS) showed that decreased mobility, defined as a gait speed less than 1 m/sec, occurred earlier in life among HIV-positive men than in HIV-negative men.

In the general aging population, slow gait speed is a predictor for lower extremity limitations, hospitalization, and death, and in more recent MACS studies was associated with increased hemoglobin A_1C levels, as well as neurocognitive impairment.

“Hemoglobin A_1C is an intervenable target, and perhaps it will help to slow the decline in gait speed,” Dr. Althoff said.
 

Reduce ‘healthspan’ disparities

The goal for treating aging adults with HIV “is to reduce the disparity in healthspan between people with HIV compared to people without HIV by delaying or eliminating the onset of comorbidities among people with HIV,” she said.

The gerontological concept of extending “healthspan” – the duration of life without significant comorbidities – is to target common mechanisms of aging, thereby delaying the onset of more than one age-related disease at the same time.

“Crude translation of this concept to the population of aging with HIV includes reducing that gap in comorbidity-free survival in people with versus without HIV,” she said.

Modification of care models from geriatrics may help infectious disease specialists manage adults with HIV who have increasingly complex needs.

For example, the geriatric “5 M” model emphasizes focusing on issues of mind (mentation, dementia, delirium, depression), mobility (impaired gait and balance, as well as fall prevention), medications (reducing polypharmacy, optimal prescribing), multicomplexity (multiple morbidities and complex bio-psycho-social situations), and “matters most” (each patient’s individual meaningful health outcome goals and care preferences).

Changing exposures that may influence the pattern of comorbidities for patients with HIV in the future include earlier start on ART, shorter duration of uncontrolled viremia, compared with older populations, newer and less toxic ARTs, long-term viral suppression, and risk factor interventions, Dr. Althoff concluded.

Dr. Lampiris noted that “patients who have initiated therapy in the last 5-10 years are more likely to initiate antiretroviral therapy at higher CD4 counts, and less likely to experience long-term toxicities of antiretroviral therapy. However, African Americans, Hispanics and HIV-positive women continue to lag behind others with regard to timely initiation of treatment.

“In addition there are toxicities associated with the newer agents, particularly weight gain, which disproportionately affect African Americans and women and which may be made worse by poverty, food insecurity, and other health-related behaviors.”

Dr. Athloff’s work is supported by grants from the National Institutes for Health. She disclosed serving as a consultant to the NIH-funded All of US study and to MediQ, and as an adviser to TrioHealth. Dr. Lampiris reported having no disclosures.

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

A smartphone app that combines passively collected physiologic data from wearable devices, such as fitness trackers, and self-reported symptoms can discriminate between COVID-19–positive and –negative individuals among those who report symptoms, new data suggest.

LDProd/Getty Images

After analyzing data from more than 30,000 participants, researchers from the Digital Engagement and Tracking for Early Control and Treatment (DETECT) study concluded that adding individual changes in sensor data improves models based on symptoms alone for differentiating symptomatic persons who are COVID-19 positive and symptomatic persons who are COVID-19 negative.

The combination can potentially identify infection clusters before wider community spread occurs, Giorgio Quer, PhD, and colleagues report in an article published online Oct. 29 in Nature Medicine. DETECT investigators note that marrying participant-reported symptoms with personal sensor data, such as deviation from normal sleep duration and resting heart rate, resulted in an area under the curve (AUC) of 0.80 (interquartile range [IQR], 0.73-0.86) for differentiating between symptomatic individuals who were positive and those who were negative for COVID-19.

“By better characterizing each individual’s unique baseline, you can then identify changes that may indicate that someone has a viral illness,” said Dr. Quer, director of artificial intelligence at Scripps Research Translational Institute in La Jolla, Calif. “In previous research, we found that the proportion of individuals with elevated resting heart rate and sleep duration compared with their normal could significantly improve real-time detection of influenza-like illness rates at the state level,” he said in an interview.

Thus, continuous passively captured data may be a useful adjunct to bricks-and-mortar site testing, which is generally a one-off or infrequent sampling assay and is not always easily accessible, he added. Furthermore, traditional screening with temperature and symptom reporting is inadequate. An elevation in temperature is not as common as frequently believed for people who test positive for COVID-19, Dr. Quer continued. “Early identification via sensor variables of those who are presymptomatic or even asymptomatic would be especially valuable, as people may potentially be infectious during this period, and early detection is the ultimate goal,” Dr. Quer said.

According to his group, adding these physiologic changes from baseline values significantly outperformed detection (P < .01) using a British model described in an earlier study by by Cristina Menni, PhD, and associates. That method, in which symptoms were considered alone, yielded an AUC of 0.71 (IQR, 0.63-0.79).

According to Dr. Quer, one in five Americans currently wear an electronic device. “If we could enroll even a small percentage of these individuals, we’d be able to potentially identify clusters before they have the opportunity to spread,” he said.
 

DETECT study details

During the period March 15 to June 7, 2020, the study enrolled 30,529 participants from all 50 states. They ranged in age from younger than 35 years (23.1%) to older than 65 years (12.8%); the majority (63.5%) were aged 35-65 years, and 62% were women. Sensor devices in use by the cohort included Fitbit activity trackers (78.4%) and Apple HealthKit (31.2%).

Participants downloaded an app called MyDataHelps, which collects smartwatch and activity tracker information, including self-reported symptoms and diagnostic testing results. The app also monitors changes from baseline in resting heart rate, sleep duration, and physical activity, as measured by steps.

Overall, 3,811 participants reported having at least one symptom of some kind (e.g., fatigue, cough, dyspnea, loss of taste or smell). Of these, 54 reported testing positive for COVID-19, and 279 reported testing negative.

Sleep and activity were significantly different for the positive and negative groups, with an AUC of 0.68 (IQR, 0.57-0.79) for the sleep metric and 0.69 (IQR, 0.61-0.77) for the activity metric, suggesting that these parameters were more affected in COVID-19–positive participants.

When the investigators combined resting heart rate, sleep, and activity into a single metric, predictive performance improved to an AUC of 0.72 (IQR, 0.64-0.80).

The next step, Dr. Quer said, is to include an alert to notify users of possible infection.
 

Alerting users to possible COVID-19 infection

In a similar study, an alert feature was already incorporated. The study, led by Michael P. Snyder, PhD, director of the Center for Genomics and Personalized Medicine at Stanford (Calif.) University, will soon be published online in Nature Biomedical Engineering. In that study, presymptomatic detection of COVID-19 was achieved in more than 80% of participants using resting heart rate.

“The median is 4 days prior to symptom formation,” Dr. Snyder said in an interview. “We have an alarm system to notify people when their heart rate is elevated. So a positive signal from a smartwatch can be used to follow up by polymerase chain reaction [testing].”

Dr. Snyder said these approaches offer a roadmap to containing widespread infections. “Public health authorities need to be open to these technologies and begin incorporating them into their tracking,” he said. “Right now, people do temperature checks, which are of limited value. Resting heart rate is much better information.”

Although the DETECT researchers have not yet received feedback on their results, they believe public health authorities could recommend the use of such apps. “These are devices that people routinely wear for tracking their fitness and sleep, so it would be relatively easy to use the data for viral illness tracking,” said co–lead author Jennifer Radin, PhD, an epidemiologist at Scripps. “Testing resources are still limited and don’t allow for routine serial testing of individuals who may be asymptomatic or presymptomatic. Wearables can offer a different way to routinely monitor and screen people for changes in their data that may indicate COVID-19.”

The marshaling of data through consumer digital platforms to fight the coronavirus is gaining ground. New York State and New Jersey are already embracing smartphone apps to alert individuals to possible exposure to the virus.

More than 710,000 New Yorkers have downloaded the COVID NY Alert app, launched in October to help protect individuals and communities from COVID-19 by sending alerts without compromising privacy or personal information. “Upon receiving a notification about a potential exposure, users are then able to self-quarantine, get tested, and reduce the potential exposure risk to family, friends, coworkers, and others,” Jonah Bruno, a spokesperson for the New York State Department of Health, said in an interview.

And recently the Mayo Clinic and Safe Health Systems launched a platform to store COVID-19 testing and vaccination data.

Both the Scripps and Stanford platforms are part of a global technologic response to the COVID-19 pandemic. Prospective studies, led by device manufacturers and academic institutions, allow individuals to voluntarily share sensor and clinical data to address the crisis. Similar approaches have been used to track COVID-19 in large populations in Germany via the Corona Data Donation app.

The study by Dr. Quer and colleagues was funded by a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. One coauthor reported grants from Janssen and personal fees from Otsuka and Livongo outside of the submitted work. The other authors have disclosed no relevant financial relationships. Dr. Snyder has ties to Personalis, Qbio, January, SensOmics, Protos, Mirvie, and Oralome.
 

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

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Black patients may be significantly less likely to receive eradication testing after treatment for Helicobacter pylori infection than patients of other races/ethnic groups, based on a retrospective analysis of more than 1,700 individuals.

Patho/Wikimedia Commons/CC BY-SA 3.0

This disparity may exacerbate the already increased burden of H. pylori infection and gastric cancer among Black individuals, according to principal author David A. Leiman, MD, MSHP, of Duke University Medical Center in Durham, N.C.

“H. pylori infection disproportionately affects racial/ethnic minorities and those of lower socioeconomic status,” Dr. Leiman, coauthor Julius Wilder, MD, PhD, of Duke University in Durham, and colleagues wrote in their abstract presented at the annual meeting of the American College of Gastroenterology. “ACG guidelines recommend treatment for H. pylori infection followed by confirmation of cure. Adherence to these recommendations varies and its impact on practice patterns is unclear. This study characterizes the management of H. pylori infection and predictors of guideline adherence.”

The investigators analyzed electronic medical records from 1,711 patients diagnosed with H. pylori infection through the Duke University Health System between June 2016 and June 2018, most often (71%) via serum antibody test. Approximately two-thirds of those diagnosed were non-White (66%) and female (63%). Out of 1,711 patients, 622 (36%) underwent eradication testing, of whom 559 (90%) were cured.

Despite publication of the ACG H. pylori guideline midway through the study (February 2017), testing rates dropped significantly from 43.1% in 2016 to 35.9% in 2017, and finally 25.5% in 2018 (P < .0001).

“These findings are consistent with other work that has shown low rates of testing to confirm cure in patients treated for H. pylori,” Dr. Leiman said. “There remains a disappointingly low number of patients who are tested for cure.”

Across the entire study period, patients were significantly more likely to undergo eradication testing if they were treated in the gastroenterology department (52.4%), compared with rates ranging from 33% to 34.6% for internal medicine, family medicine, and other departments (P < .001).

Across all departments, Black patients underwent eradication testing significantly less often than patients of other races/ethnicities, at a rate of 30.5% versus 32.2% for White patients, 35.1% for Asian patients, and 36.7% for patients who were of other backgrounds (P < .001). Compared with White patients, Black patients were 38% less likely to undergo eradication testing (odds ratio, 0.62; 95% confidence interval, 0.48-0.79).

Dr. Leiman noted that these findings contrast with a study by Dr. Shria Kumar and colleagues from earlier this year, which found no racial disparity in eradication testing within a Veterans Health Affairs cohort.

“Black patients are significantly less likely to undergo testing for eradication than [patients of other races/ethnicities],” Dr. Leiman said. “More work is needed to understand the mechanisms driving this disparity.” He suggested a number of possible contributing factors, including provider knowledge gaps, fragmented care, and social determinants of health.

“It is clear that a greater emphasis on characterizing and addressing the social determinants of health, including poverty, education, and location, are needed,” Dr. Leiman said. “Although health systems are not solely responsible for the known and ongoing observations of disparities in care, interventions must be identified and implemented to mitigate these issues.” Such interventions would likely require broad participation, he said, including policy makers, health systems, and individual practitioners.

“We plan to perform a prospective mixed methods study to contextualize which social determinants are associated with a decreased likelihood of receiving appropriate eradication testing by exploring barriers at patient, practitioner, and health-system levels,” Dr. Leiman said. “Ultimately, we aim to leverage these findings to develop an evidence-based intervention to circumnavigate those identified barriers, thereby eliminating the observed disparities in H. pylori care.”

According to Gregory L. Hall, MD, of Northeast Ohio Medical University, Rootstown, and Case Western Reserve University, Cleveland, and codirector of the Partnership for Urban Health Research, Atlanta, the higher rate of H. pylori infection in Black individuals may stem partly from genetic factors.

“Studies have shown that African Americans with a higher proportion of African ancestry have higher rates of H. pylori, suggesting a genetic component to this increased risk,” he said.

Still, Dr. Hall, who is the author of the book Patient-Centered Clinical Care for African Americans, went on to emphasize appropriate H. pylori management and recognition of racial disparities in medicine.

“The ability to test for, treat, and confirm eradication of H. pylori infections represents a great opportunity to improve quality of life through decreased gastritis, gastric ulcers, and gastric cancer,” he said. “[The present findings] show yet another disparity in our clinical care of African Americans that needs increased awareness among providers to these communities.”

Rotonya Carr, MD, of the Hospital of the University of Pennsylvania, Philadelphia, and lead author of a recent publication addressing racism and health disparities in gastroenterology, said the findings of the present study add weight to a known equity gap.

“These data are concerning in view of the twofold higher prevalence of H. pylori seropositivity and twofold higher incidence of gastric cancer in Black patients, compared with White patients,” Dr. Carr said. “These and other data support a comprehensive approach to reduce GI disparities that includes targeted education of both GI specialists and referring providers.”

According to Dr. Leiman, individual practitioners may work toward more equitable outcomes through a comprehensive clinical approach, regardless of patient race or ethnicity.

“Clinicians should consider H. pylori therapy an episode of care that spans diagnosis, treatment, and confirmation of cure,” he said. “Closing the loop in that episode by ensuring eradication is vital to conforming with best practices, and to reduce patients’ long-term risks.”The investigators disclosed relationships with Exact Sciences, Guardant Health, and Phathom Pharmaceuticals. Dr. Hall and Dr. Carr reported no relevant conflicts of interest.

SOURCE: Reichstein J et al. ACG 2020. Abstract S1332.

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

Editors in chief at 10 leading family medicine journals have banded together to address systemic racism in research, health care, and the medical profession.

Sumi Sexton, MD, editor in chief of American Family Physician (AFP), said in an interview she had been working on changes at her journal that would answer the need for action that was made clear by this summer’s Black Lives Matter protests and realized the issue was much bigger than one journal. She proposed the collaboration with the other editors.

The editors wrote a joint statement explaining what they plan to do collectively. It was published online Oct. 15 ahead of print and will be published in all 10 journals at the beginning of the year.

Following the action by family medicine editors, the American College of Physicians issued a statement expressing commitment to being an antiracist organization. It calls on all doctors to speak out against hate and discrimination and to act against institutional and systemic racism. The statement also apologizes for the organization’s own past actions: “ACP acknowledges and regrets its own historical organizational injustices and inequities, and past racism, discrimination and exclusionary practices throughout its history, whether intentional or unintentional, by act or omission.”


 

Family medicine journals plan changes

Changes will differ at each family medicine publication, according to Sexton and other interviewees. Some specific changes at AFP, for example, include creating a medical editor role dedicated to diversity, equity, and inclusion to ensure that content is not only accurate but also that more content addresses racism, Dr. Sexton said.

AFP is creating a Web page dedicated to diversity and will now capitalize the word “Black” in racial and cultural references. Recent calls for papers have included emphasis on finding authors from underrepresented groups and on mentoring new authors.

“We really need to enable our colleagues,” Dr. Sexton said.

The journals are also pooling their published research on topics of racism and inclusion and have established a joint bibliography.

The steps are important, Dr. Sexton said, because reform in research will start a “cascade of action” that will result in better patient care.

“Our mission is to care for the individual as a whole person,” Dr. Sexton said. “This is part of that mission.”
 

Increasing diversity on editorial boards

Family physician Kameron Leigh Matthews, MD, chief medical officer for the Veterans Health Administration, praised the journals’ plan.

She noted that the groups are addressing diversity on their editorial boards, as well as evaluating content. Effective change must also happen regarding the people reviewing the content, she said in an interview. “It has to be both.

“I’m very proud as a family physician that our editors came together and are giving the right response. It’s not enough to say we stand against racism. They’re actually offering concrete actions that they will take as editors, and that will influence health care,” she said.

Dr. Matthews pointed to an example of what can happen when the editorial process fails and racism is introduced in research.

She cited the retraction of an article in the Journal of the American Heart Association entitled, “Evolution of Race and Ethnicity Considerations for the Cardiology Workforce.” The article advocated for ending racial and ethnic preferences in undergraduate and medical school admissions.

The American Heart Association said the article concluded “incorrectly that Black and Hispanic trainees in medicine are less qualified than White and Asian trainees.” The article had “rightfully drawn criticism for its misrepresentations and conclusions,” the AHA said, adding that it would launch an investigation into how the article came to be published.

Dr. Matthews says that’s why it’s so important that, in their statement, the family medicine editors vow to address not only the content but also the editing process to avoid similar systemic lapses.

Dr. Matthews added that, because the proportion of physicians from underrepresented groups is small – only 5% of physicians are Black and 6% are Hispanic – it is vital, as recommended in the editors’ statement, to mentor researchers from underrepresented groups and to reach out to students and residents to be coauthors.

“To sit back and say there’s not enough to recruit from is not sufficient,” Dr. Matthews said. “You need to recognize that you need to assist with expanding the pool.”

She also said she would like to see the journals focus more heavily on solutions to racial disparities in health care rather than on pointing them out.

At the Journal of Family Practice (JFP), Editor in Chief John Hickner, MD, said adding diversity to the editorial board is a top priority. He also reiterated that diversity in top leadership is a concern across all the journals, inasmuch as only 1 of the 10 editors in chief is a person of color.

As an editor, he said, he will personally, as well as through family medicine department chairs, be seeking authors who are members of underrepresented groups and that he will be assisting those who need help.

“I’m committed to giving them special attention in the editorial process,” he said.

Dr. Hickner said the 10 journals have also committed to periodically evaluate whether their approaches are making substantial changes. He said the editors have vowed to meet at least once a year to review progress “and hold each other accountable.”

Statement authors, in addition to Dr. Sexton and Dr. Hickner, include these editors in chief: Caroline R. Richardson, MD, Annals of Family Medicine; Sarina B. Schrager, MD, FPM; Marjorie A. Bowman, MD, The Journal of the American Board of Family Medicine; Christopher P. Morley, PhD, PRiMER; Nicholas Pimlott, MD, PhD, Canadian Family Physician; John W. Saultz, MD, Family Medicine; and Barry D. Weiss, MD, FP Essentials.

The authors have disclosed no relevant financial relationships. The Journal of Family Practice is owned by the same news organization as this publication.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

The latest recommendations from sports cardiologists on getting athletes with COVID-19 back on the playing field safely emphasize a more judicious approach to screening for cardiac injury.

The new recommendations, made by the American College of Cardiology’s Sports and Exercise Cardiology Section, are for adult athletes in competitive sports and also for two important groups: younger athletes taking part in competitive high school sports and older athletes aged 35 and older, the Masters athletes, who continue to be active throughout their lives. The document was published online in JAMA Cardiology.

Because of the evolving nature of knowledge about COVID-19, updates on recommendations for safe return to play for athletes of all ages will continue to be made, senior author Aaron L. Baggish, MD, director of the cardiovascular performance program at Massachusetts General Hospital, Boston, said.

“The recommendations we released in May were entirely based on our experience taking care of hospitalized patients with COVID-19; we had no athletes in this population. We used a lot of conservative guesswork around how this would apply to otherwise healthy athletes,” Dr. Baggish said in an interview.

“But as sports started to open up, and we started to see large numbers of first professional and then college athletes come back into training, we realized that we needed to stop and ask whether the recommendations we put forward back in May were still appropriate,” Dr. Baggish said.

“Once we started to actually get into the trenches with these athletes, literally hundreds of them, and applying the testing strategies that we had initially recommended in everybody, we realized that we probably had some room for improvement, and that’s why we reconvened, to make these revisions,” he said.

Essentially, the recommendations now urge less cardiac testing. “Cardiac injury is not as common as we may have originally thought,” said Dr. Baggish.

“In the early days of COVID, people who were hospitalized had evidence of heart injury, and so we wondered if that prevalence would also be applicable to otherwise young, healthy people who got COVID. If that had been the case, we would have been in big trouble with respect to getting people back into sports. So this is why we started with a conservative screening approach and a lot of testing in order to not miss a huge burden of disease,” he said.

“But what we’ve learned over the past few months is that young people who get either asymptomatic or mild infection appear to have very, very low risk of having associated heart injury, so the need for testing in that population, when people who have infections recover fully, is almost certainly not going to be high yield,” Dr. Baggish said.
 

First iteration of the recommendations

Published in May in the early weeks of the pandemic, the first recommendations for safe return to play said that all athletes should stop training for at least 2 weeks after their symptoms resolve, then undergo “careful, clinical cardiovascular evaluation in combination with cardiac biomarkers and imaging.”

Additional testing with cardiac MRI, exercise testing, or ambulatory rhythm monitoring was to be done “based on the clinical course and initial testing.”

But experts caution that monitoring on such a scale in everyone is unnecessary and could even be counterproductive.

“Sending young athletes for extensive testing is not warranted and could send them to unnecessary testing, cardiac imaging, and so on,” Dr. Baggish said.

Only those athletes who continue to have symptoms or whose symptoms return when they get back to their athletic activities should go on for more screening.

“There, in essence, is the single main change from May, and that is a move away from screening with testing everyone, [and instead] confining that to the people who had moderate or greater severity disease,” he said.

Both iterations of the recommendations end with the same message.

“We are at the beginning of our knowledge about the cardiotoxic effects of COVID-19 but we are gathering evidence every day,” said Dr. Baggish. “Just as they did earlier, we acknowledge that our approaches are subject to change when we learn more about how COVID affects the heart, and specifically the hearts of athletes. This will be an ongoing process.”
 

Something to lean on

The recommendations are welcome, said James E. Udelson, MD, chief of the division of cardiology at Tufts Medical Center, Boston, coauthor of an accompanying editorial.

“It was a bit of the wild west out there, because each university, each college, all with good intentions, had been all struggling to figure out what to do, and how much to do. Probably the most important message from this new paper is the fact that now there is something out there that all coaches, athletes, families, schools, trainers can get some guidance from,” Dr. Udelson said in an interview.

Refining the cardiac screening criteria was a necessary step, Dr. Udelson said.

“How much cardiac imaging do you do? That is a matter of controversy,” said Dr. Udelson, who coauthored the commentary with Tufts cardiologist Ethan Rowin, MD, and Michael A. Curtis, MEd, a certified strength and conditioning specialist at the University of Virginia, Charlottesville. “The problem is that if you use a very sensitive imaging test on a lot of people, sometimes you find things that you really didn’t need to know about. They’re really not important. And now, the athlete is told he or she cannot play for 3 months because they might have myocarditis.

“Should we be too sensitive, meaning do we want to pick up anything no matter whether it’s important or not?” he added. “There will be a lot of false positives, and we are going to disqualify a lot of people. Or do you tune it a different way?”

Dr. Udelson said he would like to see commercial sports donate money to support research into the potential cardiotoxicity of COVID-19.

“If the organizations that benefit from these athletes, like the National Collegiate Athletic Association and professional sports leagues, can fund some of this research, that would be a huge help,” Dr. Udelson said.

“These are the top sports cardiologists in the country, and they have to start somewhere, and these are all based on what we know right now, as well as their own extensive experience. We all know that we are just at the beginning of our knowledge of this. But we have to have something to guide this huge community out there that is really thirsty for help.”

Dr. Baggish reports receiving research funding for the study of athletes in competitive sports from the National Heart, Lung, and Blood Institute; the National Football League Players Association; and the American Heart Association and receiving compensation for his role as team cardiologist from the US Olympic Committee/US Olympic Training Centers, US Soccer, US Rowing, the New England Patriots, the Boston Bruins, the New England Revolution, and Harvard University. Dr. Udelson has disclosed no relevant financial relationships.
 

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

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

Clarissa Barnes, MD, a hospitalist at Avera McKennan Hospital in Sioux Falls, S.D., and until recently medical director of Avera’s LIGHT Program, a wellness-oriented service for doctors, nurse practitioners, and physician assistants, watched the COVID-19 crisis unfold up close in her community and her hospital. Sioux Falls traced its surge of COVID patients to an outbreak at a local meatpacking plant.

“In the beginning, we didn’t know much about the virus and its communicability, although we have since gotten a better handle on that,” she said. “We had questions: Should we give patients more fluids – or less? Steroids or not? In my experience as a hospitalist I never had patients die every day on my shift, but that was happening with COVID.” The crisis imposed serious stresses on frontline providers, and hospitalists were concerned about personal safety and exposure risk – not just for themselves but for their families.

“The first time I worked on the COVID unit, I moved into the guest room in our home, apart from my husband and our young children,” Dr. Barnes said. “Ultimately I caught the virus, although I have since recovered.” Her experience has highlighted how existing issues of job stress and burnout in hospital medicine have been exacerbated by COVID-19. Even physicians who consider themselves healthy may have little emotional reserve to draw upon in a crisis of this magnitude.

“We are social distancing at work, wearing masks, not eating together with our colleagues – with less camaraderie and social support than we used to have,” she said. “I feel exhausted and there’s no question that my colleagues and I have sacrificed a lot to deal with the pandemic.” Add to that the second front of the COVID-19 crisis, Dr. Barnes said, which is “fighting the medical information wars, trying to correct misinformation put out there by people. Physicians who have been on the front lines of the pandemic know how demoralizing it can be to have people negate your first-hand experience.”

The situation has gotten better in Sioux Falls, Dr. Barnes said, although cases have started rising in the state again. The stress, while not gone, is reduced. For some doctors, “COVID reminded us of why we do what we do. Some of the usual bureaucratic requirements were set aside and we could focus on what our patients needed and how to take care of them.”
 

Taking job stress seriously

Tiffani Panek, MA, SFHM, CLHM, administrator of the division of hospital medicine at Johns Hopkins Bayview Medical Center in Baltimore, said job stress is a major issue for hospitalist groups.

“We take it seriously here, and use a survey tool to measure morale in our group annually,” she said. “So far, knock on wood, Baltimore has not been one of the big hot spots, but we’ve definitely had waves of COVID patients.”

The Bayview hospitalist group has a diversified set of leaders, including a wellness director. “They’re always checking up on our people, keeping an eye on those who are most vulnerable. One of the stressors we hadn’t thought about before was for our people who live alone. With the isolation and lockdown, they haven’t been able to socialize, so we’ve made direct outreach, asking people how they were doing,” Ms. Panek said. “People know we’ve got their back – professionally and personally. They know, if there’s something we can do to help, we will do it.”

Bayview Medical Center has COVID-specific units and non-COVID units, and has tried to rotate hospitalist assignments because more than a couple days in a row spent wearing full personal protective equipment (PPE) is exhausting, Ms. Panek said. The group also allocated a respite room just outside the biocontainment unit, with a computer and opportunities for providers to just sit and take a breather – with appropriate social distancing. “It’s not fancy, but you just have to wear a mask, not full PPE.”

The Hopkins hospitalist group’s wellness director, Catherine Washburn, MD, also a working hospitalist, said providers are exhausted, and trying to transition to the new normal is a moving target.

“It’s hard for anyone to say what our lives will look like in 6 months,” she said. “People in our group have lost family members to COVID, or postponed major life events, like weddings. We acknowledge losses together as a group, and celebrate things worth celebrating, like babies or birthdays.”
 

Greatest COVID caseload

Joshua Case, MD, hospitalist medical director for 16 acute care hospitals of Northwell Health serving metropolitan New York City and Long Island, said his group’s hospitalists and other staff worked incredibly hard during the surge of COVID-19 patients in New York. “Northwell likely cared for more COVID patients than any other health care system in the U.S., if not the world.

“It’s vastly different now. We went from a peak of thousands of cases per day down to about 70-90 new cases a day across our system. We’re lucky our system recognized that COVID could be an issue early on, with all of the multifaceted stressors on patient care,” Dr. Case said. “We’ve done whatever we could to give people time off, especially as the census started to come down. We freed up as many supportive mental health services as we could, working with the health system’s employee assistance program.”

Northwell gave out numbers for the psychiatry department, with clinicians available 24/7 for a confidential call, along with outside volunteers and a network of trauma psychologists. “Our system also provided emergency child care for staff, including hospitalists, wherever we could, drawing upon community resources,” Dr. Case added.

“We recognize that we’re all in the same foxhole. That’s been a helpful attitude – recognizing that it’s okay to be upset in a crisis and to have trouble dealing with what’s going on,” he said. “We need to acknowledge that some of us are suffering and try to encourage people to face it head on. For a lot of physicians, especially those who were redeployed here from other departments, it was important just to have us ask if they were doing okay.”

Brian Schroeder, MHA, FACHE, FHM, assistant vice president for hospital and emergency medicine for Atrium Health, based in Charlotte, N.C., said one of the biggest sources of stress on his staff has been the constant pace of change – whether local hospital protocols, state policies, or guidelines from the Centers for Disease Control and Prevention. “The updating is difficult to keep up with. A lot of our physicians get worried and anxious that they’re not following the latest guidelines or correctly doing what they should be doing to care for COVID patients. One thing we’ve done to alleviate some of that fear and anxiety is through weekly huddles with our hospital teams, focusing on changes relevant to their work. We also have weekly ‘all-hands’ meetings for our 250 providers across 13 acute and four postacute facilities.”

Before COVID, it was difficult to get everyone together as one big group from hospitals up to 5 hours apart, but with the Microsoft Teams platform, they can all meet together.

“At the height of the pandemic, we’d convene weekly and share national statistics, organizational statistics, testing updates, changes to protocols,” Mr. Schroeder said. As the pace of change has slowed, these meetings were cut back to monthly. “Our physicians feel we are passing on information as soon as we get it. They know we’ll always tell them what we know.”

Sarah Richards, MD, assistant professor of internal medicine at the University of Nebraska, Omaha, who heads the Society of Hospital Medicine’s Well-Being Task Force, formed to address staff stress in the COVID environment, said there are things that health care systems can do to help mitigate job stress and burnout. But broader issues may need to be addressed at a national level. “SHM is trying to understand work-related stress – and to identify resources that could support doctors, so they can spend more of their time doing what they enjoy most, which is taking care of patients,” she said.

“We also recognize that people have had very different experiences, depending on geography, and at the individual level stressors are experienced very differently,” Dr. Richard noted. “One of the most common stressors we’ve heard from doctors is the challenge of caring for patients who are lonely and isolated in their hospital rooms, suffering and dying in new ways. In low-incidence areas, doctors are expressing guilt because they aren’t under as much stress as their colleagues. In high-incidence areas, doctors are already experiencing posttraumatic stress disorder.”

SHM’s Well-Being Task Force is working on a tool to help normalize these stressors and encourage open conversations about mental health issues. A guide called “HM COVID Check-in Guide for Self & Peers” is designed to help hospitalists break the culture of silence around well-being and burnout during COVID-19 and how people are handling and processing the pandemic experience. It is expected to be completed later this year, Dr. Richards said. Other SHM projects and resources for staff support are also in the works.
 

The impact on women doctors

In a recent Journal of Hospital Medicine article entitled “Collateral Damage: How COVID-19 is Adversely Impacting Women Physicians,” hospitalist Yemisi Jones, MD, medical director of continuing medical education at Cincinnati Children’s Hospital Medical Center, and colleagues argue that preexisting gender inequities in compensation, academic rank and leadership positions for physicians have made the COVID-19 crisis even more burdensome on female hospitalists.¹

“Increased childcare and schooling obligations, coupled with disproportionate household responsibilities and an inability to work from home, will likely result in female hospitalists struggling to meet family needs while pandemic-related work responsibilities are ramping up,” they write. COVID may intensify workplace inequalities, with a lack of recognition of the undue strain that group policies place on women.

“Often women suffer in silence,” said coauthor Jennifer O’Toole, MD, MEd, director of education in the division of hospital medicine at Cincinnati Children’s Hospital Medical Center and program director of the internal medicine–pediatrics residency. “We are not always the best self-advocates, although many of us are working on that.”

When women in hospital medicine take leadership roles, these often tend to involve mutual support activities, taking care of colleagues, and promoting collaborative work environments, Dr. Jones added. The stereotypical example is the committee that organizes celebrations when group members get married or have babies.

These activities can take a lot of time, she said. “We need to pay attention to that kind of role in our groups, because it’s important to the cohesiveness of the group. But it often goes unrecognized and doesn’t translate into the currency of promotion and leadership in medicine. When women go for promotions in the future, how will what happened during the COVID crisis impact their opportunities?”

What is the answer to overcoming these systemic inequities? Start with making sure women are part of the leadership team, with responsibilities for group policies, schedules, and other important decisions. “Look at your group’s leadership – particularly the higher positions. If it’s not diverse, ask why. ‘What is it about the structure of our group?’ Make a more concerted effort in your recruitment and retention,” Dr. Jones said.

The JHM article also recommends closely monitoring the direct and indirect effects of COVID-19 on female hospitalists, inquiring specifically about the needs of women in the organization, and ensuring that diversity, inclusion, and equity efforts are not suspended during the pandemic. Gender-based disparities in pay also need a closer look, and not just one time but reviewed periodically and adjusted accordingly.

Mentoring for early career women is important, but more so is sponsorship – someone in a high-level leadership role in the group sponsoring women who are rising up the career ladder, Dr. O’Toole said. “Professional women tend to be overmentored and undersponsored.”
 

What are the answers?

Ultimately, listening is key to try to help people get through the pandemic, Dr. Washburn said. “People become burned out when they feel leadership doesn’t understand their needs or doesn’t hear their concerns. Our group leaders all do clinical work, so they are seen as one of us. They try very hard; they have listening ears. But listening is just the first step. Next step is to work creatively to get the identified needs met.”

A few years ago, Johns Hopkins developed training in enhanced communication in health care for all hospital providers, including nurses and doctors, encouraging them to get trained in how to actively listen and address their patients’ emotional and social experiences as well as disease, Dr. Washburn explained. Learning how to listen better to patients can enhance skills at listening to colleagues, and vice versa. “We recognize the importance of better communication – for reducing sentinel events in the hospital and also for preventing staff burnout.”

Dr. Barnes also does physician coaching, and says a lot of that work is helping people achieve clarity on their core values. “Healing patients is a core identify for physicians; we want to take care of people. But other things can get in the way of that, and hospitalist groups can work at minimizing those barriers. We also need to learn, as hospitalists, that we work in a group. You need to be creative in how you do your team building, especially now, when you can no longer get together for dinner. Whatever it is, how do we bring our team back together? The biggest source of support for many hospitalists, beyond their family, is the group.”

Dr. Case said there is a longer-term need to study the root causes of burnout in hospitalists and to identify the issues that cause job stress. “What is modifiable? How can we tackle it? I see that as big part of my job every day. Being a physician is hard enough as it is. Let’s work to resolve those issues that add needlessly to the stress.”

“I think the pandemic brought a magnifying glass to how important a concern staff stress is,” Ms. Panek said. Resilience is important.

“We were working in our group on creating a culture that values trust and transparency, and then the COVID crisis hit,” she said. “But you can still keep working on those things. We would not have been as good or as positive as we were in managing this crisis without that preexisting culture to draw upon. We always said it was important. Now we know that’s true.”
 

Reference

1. Jones Y et al. Collateral Damage: How COVID-19 Is Adversely Impacting Women Physicians. J Hosp Med. 2020 August;15(8):507-9.

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Plagued by false starts, a few dashed hopes, but with perhaps a glimmer of light on the horizon, the race to find an effective treatment for COVID-19 continues. At last count, more than 300 treatments and 200 vaccines were in preclinical or clinical development (not to mention the numerous existing agents that are being evaluated for repurposing).

There is also a renewed interest in cannabinoid therapeutics — in particular, the nonpsychoactive agent cannabidiol (CBD) and the prospect of its modulating inflammatory and other disease-associated clinical indices, including SARS-CoV-2–induced viral load, hyperinflammation, the cytokine storm, and acute respiratory distress syndrome (ARDS).

Long hobbled by regulatory, political, and financial barriers, CBD’s potential ability to knock back COVID-19–related inflammation might just open doors that have been closed for years to CBD researchers.
 

Why CBD and why now?

CBD and the resulting therapeutics have been plagued by a complicated association with recreational cannabis use. It’s been just 2 years since CBD-based therapeutics moved into mainstream medicine — the US Food and Drug Administration (FDA) approved Epidiolex oral solution for the treatment of Lennox-Gastaut syndrome and Dravet syndrome, and in August, the FDA approved it for tuberous sclerosis complex.

CBD’s mechanism of action has not been fully elucidated, but on the basis of its role in immune responses — well described in research spanning more than two decades — it›s not surprising that cannabinoid researchers have thrown their hats into the COVID-19 drug development ring.

The anti-inflammatory potential of CBD is substantial and appears to be related to the fact that it shares 20 protein targets common to inflammation-related pathways, Jenny Wilkerson, PhD, research assistant professor at the University of Florida School of Pharmacy, Gainesville, Florida, explained to Medscape Medical News.

Among the various trials that are currently recruiting or are underway is one that is slated for completion this fall. CANDIDATE (Cannabidiol for COVID-19 Patients With Mild-to-Moderate COVID-19) is a randomized, controlled, double-blind study led by Brazilian researchers at the University of São Paulo. The study, which began recruitment this past August, enrolled 100 patients, 50 in the active treatment group (who received capsulated CBD 300 mg daily for 14 days plus pharmacologic therapy [antipyretics] and clinical measures) and 50 who received placebo.

The primary outcome is intended to help clarify the potential role of oral CBD for preventing COVID-19 disease progression, modifying disease-associated clinical indices, and modulating inflammatory parameters, such as the cytokine storm, according to lead investigator Jose Alexandre de Souza Crippa, MD, PhD, professor of neuropsychology at the Ribeirao Preto Medical School at the University of São Paulo in Brazil, in the description of the study on clinicaltrials.gov. Crippa declined to provide any additional information about the trial in an email to Medscape Medical News.
 

Calming or preventing the storm

While Crippa and colleagues wrap up their CBD trial in South America, several North American and Canadian researchers are seeking to clarify and address one of the most therapeutically challenging aspects of SARS-CoV-2 infection — the lung macrophage–orchestrated hyperinflammatory response.

Although hyperinflammation is not unique to SARS-CoV-2 infection, disease severity and COVID-19–related mortality have been linked to this rapid and prolonged surge of inflammatory cytokines (eg, interleukin 6 [IL-6], IL-10, tumor necrosis factors [TNF], and chemokines) and the cytokine storm.

“When you stimulate CB2 receptors (involved in fighting inflammation), you get a release of the same inflammatory cytokines that are involved in COVID,” Cecilia Costiniuk, MD, associate professor and researcher at the Research Institute of the McGill University Health Center, Montreal, Canada, told Medscape Medical News.

“So, if you can act on this receptor, you might be able to reduce the release of those damaging cytokines that are causing ARDS, lung damage, etc,” she explained. Targeting these inflammatory mediators has been a key strategy in research aimed at reducing COVID-19 severity and related mortality, which is where CBD comes into play.

“CBD is a very powerful immune regulator. It keeps the [immune] engine on, but it doesn’t push the gas pedal, and it doesn’t push the brake completely,” Babak Baban, PhD, professor and immunologist at the Dental College of Georgia at Augusta University, told Medscape Medical News.

To explore the effectiveness of CBD in reducing hyperactivated inflammatory reactions, Baban and colleagues examined the potential of CBD to ameliorate ARDS in a murine model. The group divided wild-type male mice into sham, control, and treatment groups.

The sham group received intranasal phosphate buffered saline; the treatment and control groups received a polyriboinosinic:polycytidylic acid (poly I:C) double-stranded RNA analogue (100 mcg daily for 3 days) to simulate the cytokine storm and clinical ARDS symptoms.

Following the second poly I:C dose, the treatment group received CBD 5 mg/kg intraperitoneally every other day for 6 days. The mice were sacrificed on day 8.

The study results, published in July in Cannabis and Cannabinoid Research, first confirmed that the poly I:C model simulated the cytokine storm in ARDS, reducing blood oxygen saturation by as much as 10% (from ±81.6% to ±72.2%).

Intraperitoneally administered CBD appeared to reverse these ARDS-like trends. “We observed a significant improvement in severe lymphopenia, a mild decline in the ratio of neutrophils to T cells, and significant reductions in levels of [inflammatory and immune factors] IL-6, IFN-gamma [interferon gamma], and in TNF-alpha after the second CBD dose,” Baban said.

There was also a marked downregulation in infiltrating neutrophils and macrophages in the lung, leading to partial restoration of lung morphology and structure. The investigators write that this suggests “a counter inflammatory role for CBD to limit ARDS progression.”

Additional findings from a follow-up study published in mid-October “provide strong data that CBD may partially assert its beneficial and protective impact through its regulation of the apelin peptide,” wrote Baban in an email to Medscape Medical News.

“Apelin may also be a reliable biomarker for early diagnosis of ARDS in general, and in COVID-19 in particular,” he wrote.

Questions remain concerning dose response and whether CBD alone or in combination with other phytocannabinoids is more effective for treating COVID-19. Timing is likewise unclear.

Baban explained that as a result of the biphasic nature of COVID-19, the “sweet spot” appears to be just before the innate immune response progresses into an inflammation-driven response and fibrotic lung damage occurs.

But Wilkerson isn’t as convinced. She said that as with a thermostat, the endocannabinoid system needs tweaking to get it in the right place, that is, to achieve immune homeostasis. The COVID cytokine storm is highly unpredictable, she added, saying, “Right now, the timing for controlling the COVID cytokine storm is really a moving target.”
 

Is safety a concern?

Safety questions are expected to arise, especially in relation to COVID-19. CBD is not risk free, and one size does not fit all. Human CBD studies report gastrointestinal and somnolent effects, as well as drug-drug interactions.

Findings from a recent systematic review of randomized, controlled CBD trials support overall tolerability, suggesting that serious adverse events are rare. Such events are believed to be related to drug-drug interactions rather than to CBD itself. On the flip side, it is nonintoxicating, and there does not appear to be potential for abuse.

“It’s generally well tolerated,” Wilkerson said. “There’ve now been several clinical trials in numerous patient population settings where basically the only time you really start to have issues is where you have patients on very select agents. But this is where a pharmacist would come into play.”

Costiniuk agreed: “Just because it’s cannabis, it doesn’t mean that there’s going to be strange or unusual effects; these people [ie, those with severe COVID-19] are in the hospital and monitored very closely.”
 

Delving into the weeds: What’s next?

Although non-COVID-19 cannabinoid researchers have encountered regulatory roadblocks, several research groups that have had the prescience to dive in at the right time are gaining momentum.

Baban’s team has connected with one of the nation’s few academic laboratories authorized to work with the SARS-CoV-2 virus and are awaiting protocol approval so that they can reproduce their research, this time using two CBD formulations (injectable and inhaled).

If findings are positive, they will move forward quickly to meet with the FDA, Baban said, adding that the team is also collaborating with two organizations to conduct human clinical trials in hopes of pushing up timing.

The initial article caught the eye of the World Health Organization, which included it in its global literature on the coronavirus resource section.

Israeli researchers have also been quite busy. InnoCan Pharma and Tel Aviv University are collaborating to explore the potential for CBD-loaded exosomes (minute extracellular particles that mediate intracellular communication, including via innate and adaptive immune responses). The group plans to use these loaded exosomes to target and facilitate recovery of COVID-19–damaged lung cells.

From a broader perspective, the prospects for harnessing cannabinoids for immune modulation will be more thoroughly explored in a special issue of Cannabis and Cannabinoid Research, which has extended its current call for papers, studies, abstracts, and conference proceedings until the end of December.

Like many of the therapeutic strategies under investigation for the treatment of COVID-19, studies in CBD may continue to raise more questions than answers.

Still, Wilkerson is optimistic. “Taken together, these studies along with countless others suggest that the complex pharmacophore of Cannabis sativa may hold therapeutic utility to treat lung inflammation, such as what is seen in a COVID-19 cytokine storm,» she told Medscape Medical News. “I’m very excited to see what comes out of the research.”

Baban, Wilkerson, and Costiniuk have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.