Journal of Clinical Outcomes Management

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

The improvement in survival in many cancer types that is seen with immune checkpoint inhibitors (ICIs), when compared to control therapies, is not affected by the patient’s sex, age, or Eastern Cooperative Oncology Group (ECOG) performance status (PS), according to a new meta-analysis.

Therefore, treatment with these immunotherapies should not be withheld on the basis of these factors, the authors concluded.

Asked whether there have been such instances of withholding ICIs, lead author Yucai Wang, MD, PhD, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News: “We did this study solely based on scientific questions we had and not because we were seeing any bias at the moment in the use of ICIs.

“And we saw that the survival benefits were very similar across all of the categories [we analyzed], with a survival benefit of about 20% from immunotherapy across the board, which is clinically meaningful,” he added.

The study was published online August 7 in JAMA Network Open.

“The comparable survival advantage between patients of different sex, age, and ECOG PS may encourage more patients to receive ICI treatment regardless of cancer types, lines of therapy, agents of immunotherapy, and intervention therapies,” the authors commented.

Wang noted that there have been conflicting reports in the literature suggesting that male patients may benefit more from immunotherapy than female patients and that older patients may benefit more from the same treatment than younger patients.

However, there are also suggestions in the literature that women experience a stronger immune response than men and that, with aging, the immune system generally undergoes immunosenescence.

In addition, the PS of oncology patients has been implicated in how well patients respond to immunotherapy.

Wang noted that the findings of past studies have contradicted each other.
 

Findings of the Meta-Analysis

The meta-analysis included 37 randomized clinical trials that involved a total of 23,760 patients with a variety of advanced cancers. “Most of the trials were phase 3 (n = 34) and conduced for subsequent lines of therapy (n = 22),” the authors explained.

The most common cancers treated with an ICI were non–small cell lung cancer and melanoma.

Pooled overall survival (OS) hazard ratios (HRs) were calculated on the basis of sex, age (younger than 65 years and 65 years and older), and an ECOG PS of 0 and 1 or higher.

Responses were stratified on the basis of cancer type, line of therapy, the ICI used, and the immunotherapy strategy used in the ICI arm.

Most of the drugs evaluated were PD-1 and PD-L1 inhibitors. The specific drugs assessed included ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab.

A total of 32 trials that involved more than 20,000 patients reported HRs for death according to the patients’ sex. Thirty-four trials that involved more than 21,000 patients reported HRs for death according to patients’ age, and 30 trials that involved more than 19,000 patients reported HRs for death according to patients’ ECOG PS.

No significant differences in OS benefit were seen by cancer type, line of therapy, agent of immunotherapy, or intervention strategy, the investigators pointed out.

There were also no differences in survival benefit associated with immunotherapy vs control therapies for patients with an ECOG PS of 0 and an ECOG PS of 1 or greater. The OS benefit was 0.81 for those with an ECOG PS of 0 and 0.79 for those with an ECOG PS of 1 or greater.

Wang has disclosed no relevant financial relationships.

This article first appeared on Medscape.com .

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

As communities wrestle with the decision to send children back to school or opt for distance learning, a key question is how many children are likely to have asymptomatic SARS-CoV-2 infections. Researchers have now found that the prevalence of asymptomatic infections in children correlates with the overall incidence of COVID-19 in the local population, according to an analysis of data from 28 U.S. children’s hospitals.

Courtesy NIAID

“The strong association between prevalence of SARS-CoV-2 in children who are asymptomatic and contemporaneous weekly incidence of COVID-19 in the general population ... provides a simple means for institutions to estimate local pediatric asymptomatic prevalence from the publicly available Johns Hopkins University database,” researchers say in an article published online August 25 in JAMA Pediatrics.

Ana Marija Sola, BS, a researcher at the University of California, San Francisco, and colleagues examined the prevalence of SARS-CoV-2 infection among 33,041 children who underwent routine testing in April and May when hospitals resumed elective medical and surgical care. The hospitals performed reverse transcription–polymerase chain reaction tests for SARS-CoV-2 RNA before surgery, clinic visits, or hospital admissions. Pediatric otolaryngologists reported the prevalence data through May 29 as part of a quality improvement project.

In all, 250 patients tested positive for the virus, for an overall prevalence of 0.65%. Across 25 geographic areas, the prevalence ranged from 0% to 2.2%. By region, prevalence was highest in the Northeast, at 0.90%, and the Midwest, at 0.87%; prevalence was lower in the West, at 0.59%, and the South, at 0.52%.

To get a sense of how those rates compared with overall rates in the same geographic areas, the researchers used the Johns Hopkins University confirmed cases database to calculate the average weekly incidence of COVID-19 for the entire population for each geographic area.

“Asymptomatic pediatric prevalence was significantly associated with weekly incidence of COVID-19 in the general population during the 6-week period over which most testing of individuals without symptoms occurred,” Ms. Sola and colleagues reported. An analysis using additional data from 11 geographic areas demonstrated that this association persisted at a later time point.

The study provides “another window on the question of how likely is it that an asymptomatic child will be carrying coronavirus,” said Susan E. Coffin, MD, MPH, an attending physician for the division of infectious diseases at Children’s Hospital of Philadelphia. However, important related questions remain, said Dr. Coffin, who was not involved with the study.

For one, it is unclear how many children remain asymptomatic in comparison with those who were in a presymptomatic phase at the time of testing. And importantly, “what proportion of these children are infectious?” said Dr. Coffin. “There is some data to suggest that children with asymptomatic infection may be less infectious than children with symptomatic infection.”

It also could be that patients seen at children’s hospitals differ from the general pediatric population. “What does this look like if you do the exact same study in a group of randomly selected children, not children who are queueing up to have a procedure? ... And what do these numbers look like now that stay-at-home orders have been lifted?” Dr. Coffin asked.

Further studies are needed to establish that detection of COVID-19 in the general population is predictive of the prevalence of SARS-CoV-2 infection in asymptomatic children, Dr. Coffin said.

The authors have disclosed no relevant financial relationships.

This article first appeared on Medscape.com.

Investigators conducting randomized controlled clinical trials to gauge the utility of convalescent plasma in COVID-19 are uncertain how studies will be affected now that the US Food and Drug Administration has given an emergency use authorization (EUA) for the therapy.

The agency’s move took many investigators by surprise. The EUA was announced at the White House the day after President Donald J. Trump accused the FDA of delaying approval of therapeutics to hurt his re-election chances.

In a memo describing the decision, the FDA cited data from some controlled and uncontrolled studies and, primarily, data from an open-label expanded-access protocol overseen by the Mayo Clinic.

At the White House, FDA Commissioner Stephen Hahn, MD, said that plasma had been found to save the lives of 35 out of every 100 who were treated. That figure was later found to have been erroneous, and many experts pointed out that Hahn had conflated an absolute risk reduction with a relative reduction. After a firestorm of criticism, Hahn issued an apology.

“The criticism is entirely justified,” he tweeted. “What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”

About 15 randomized controlled trials – out of 54 total studies involving convalescent plasma – are underway in the United States, according to ClinicalTrials.gov. The FDA’s Aug. 23 emergency authorization gave clinicians wide leeway to employ convalescent plasma in patients hospitalized with COVID-19.

The agency noted, however, that “adequate and well-controlled randomized trials remain necessary for a definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the optimal product attributes and appropriate patient populations for its use.”

But it’s not clear that people with COVID-19, especially those who are severely ill and hospitalized, will choose to enlist in a clinical trial – where they could receive a placebo – when they instead could get plasma.

“I’ve been asked repeatedly whether the EUA will affect our ability to recruit people into our hospitalized patient trial,” said Liise-anne Pirofski, MD, FIDSA, chief of the department of medicine, infectious diseases division at Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, New York. “I do not know,” she said, on a call with reporters organized by the Infectious Diseases Society of America.

“But,” she said, “I do know that the trial will continue and that we will discuss the evidence that we have with our patients and give them all that we can to help them weigh the evidence and make up their minds.”

Pirofski said the study being conducted at Montefiore and four other sites has since late April enrolled 190 patients out of a hoped-for 300.

When the study – which compares convalescent plasma to saline in hospitalized patients – was first designed, “there was not any funding for our trial and honestly not a whole lot of interest,” Pirofski told reporters. Individual donors helped support the initial rollout in late April and the trial quickly enrolled 150 patients as the pandemic peaked in the New York City area.

The National Institutes of Health has since given funding, which allowed the study to expand to New York University, Yale University, the University of Miami, and the University of Texas at Houston.
 

Hopeful, but a long way to go

Shmuel Shoham, MD, FIDSA, associate director of the transplant and oncology infectious diseases center at Johns Hopkins University School of Medicine in Baltimore, said that he’s hopeful that people will continue to enroll in his trial, which is seeking to determine if plasma can prevent COVID-19 in those who’ve been recently exposed.

“Volunteers joining the study is the only way that we’re going to get to know whether this stuff works for prevention and treatment,” Shoham said on the call. He urged physicians and other healthcare workers to talk with patients about considering trial participation.

Shoham’s study is being conducted at 30 US sites and one at the Navajo Nation. It has enrolled 25 out of a hoped-for 500 participants. “We have a long way to go,” said Shoham.

Another Hopkins study to determine whether plasma is helpful in shortening illness in nonhospitalized patients, which is being conducted at the same 31 sites, has enrolled 50 out of 600.

Shoham said recruiting patients with COVID for any study had proven to be difficult. “The vast majority of people that have coronavirus do not come to centers that do clinical trials or interventional trials,” he said, adding that, in addition, most of those “who have coronavirus don’t want to be in a trial. They just want to have coronavirus and get it over with.”

But it’s important to understand how to conduct trials in a pandemic – in part to get answers quickly, he said. Researchers have been looking at convalescent plasma for months, said Shoham. “Why don’t we have the randomized clinical trial data that we want?”

Pirofski noted that trials have also been hobbled in part by “the shifting areas of the pandemic.” Fewer cases make for fewer potential plasma donors.

Both Shoham and Pirofski also said that more needed to be done to encourage plasma donors to participate.

The US Department of Health & Human Services clarified in August that hospitals, physicians, health plans, and other health care workers could contact individuals who had recovered from COVID-19 without violating the HIPAA privacy rule.

Pirofski said she believes that trial investigators know it is legal to reach out to patients. But, she said, “it probably could be better known.”
 

This article first appeared on Medscape.com.

Investigators conducting randomized controlled clinical trials to gauge the utility of convalescent plasma in COVID-19 are uncertain how studies will be affected now that the US Food and Drug Administration has given an emergency use authorization (EUA) for the therapy.

The agency’s move took many investigators by surprise. The EUA was announced at the White House the day after President Donald J. Trump accused the FDA of delaying approval of therapeutics to hurt his re-election chances.

In a memo describing the decision, the FDA cited data from some controlled and uncontrolled studies and, primarily, data from an open-label expanded-access protocol overseen by the Mayo Clinic.

At the White House, FDA Commissioner Stephen Hahn, MD, said that plasma had been found to save the lives of 35 out of every 100 who were treated. That figure was later found to have been erroneous, and many experts pointed out that Hahn had conflated an absolute risk reduction with a relative reduction. After a firestorm of criticism, Hahn issued an apology.

“The criticism is entirely justified,” he tweeted. “What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”

About 15 randomized controlled trials – out of 54 total studies involving convalescent plasma – are underway in the United States, according to ClinicalTrials.gov. The FDA’s Aug. 23 emergency authorization gave clinicians wide leeway to employ convalescent plasma in patients hospitalized with COVID-19.

The agency noted, however, that “adequate and well-controlled randomized trials remain necessary for a definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the optimal product attributes and appropriate patient populations for its use.”

But it’s not clear that people with COVID-19, especially those who are severely ill and hospitalized, will choose to enlist in a clinical trial – where they could receive a placebo – when they instead could get plasma.

“I’ve been asked repeatedly whether the EUA will affect our ability to recruit people into our hospitalized patient trial,” said Liise-anne Pirofski, MD, FIDSA, chief of the department of medicine, infectious diseases division at Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, New York. “I do not know,” she said, on a call with reporters organized by the Infectious Diseases Society of America.

“But,” she said, “I do know that the trial will continue and that we will discuss the evidence that we have with our patients and give them all that we can to help them weigh the evidence and make up their minds.”

Pirofski said the study being conducted at Montefiore and four other sites has since late April enrolled 190 patients out of a hoped-for 300.

When the study – which compares convalescent plasma to saline in hospitalized patients – was first designed, “there was not any funding for our trial and honestly not a whole lot of interest,” Pirofski told reporters. Individual donors helped support the initial rollout in late April and the trial quickly enrolled 150 patients as the pandemic peaked in the New York City area.

The National Institutes of Health has since given funding, which allowed the study to expand to New York University, Yale University, the University of Miami, and the University of Texas at Houston.
 

Hopeful, but a long way to go

Shmuel Shoham, MD, FIDSA, associate director of the transplant and oncology infectious diseases center at Johns Hopkins University School of Medicine in Baltimore, said that he’s hopeful that people will continue to enroll in his trial, which is seeking to determine if plasma can prevent COVID-19 in those who’ve been recently exposed.

“Volunteers joining the study is the only way that we’re going to get to know whether this stuff works for prevention and treatment,” Shoham said on the call. He urged physicians and other healthcare workers to talk with patients about considering trial participation.

Shoham’s study is being conducted at 30 US sites and one at the Navajo Nation. It has enrolled 25 out of a hoped-for 500 participants. “We have a long way to go,” said Shoham.

Another Hopkins study to determine whether plasma is helpful in shortening illness in nonhospitalized patients, which is being conducted at the same 31 sites, has enrolled 50 out of 600.

Shoham said recruiting patients with COVID for any study had proven to be difficult. “The vast majority of people that have coronavirus do not come to centers that do clinical trials or interventional trials,” he said, adding that, in addition, most of those “who have coronavirus don’t want to be in a trial. They just want to have coronavirus and get it over with.”

But it’s important to understand how to conduct trials in a pandemic – in part to get answers quickly, he said. Researchers have been looking at convalescent plasma for months, said Shoham. “Why don’t we have the randomized clinical trial data that we want?”

Pirofski noted that trials have also been hobbled in part by “the shifting areas of the pandemic.” Fewer cases make for fewer potential plasma donors.

Both Shoham and Pirofski also said that more needed to be done to encourage plasma donors to participate.

The US Department of Health & Human Services clarified in August that hospitals, physicians, health plans, and other health care workers could contact individuals who had recovered from COVID-19 without violating the HIPAA privacy rule.

Pirofski said she believes that trial investigators know it is legal to reach out to patients. But, she said, “it probably could be better known.”
 

This article first appeared on Medscape.com.

Investigators conducting randomized controlled clinical trials to gauge the utility of convalescent plasma in COVID-19 are uncertain how studies will be affected now that the US Food and Drug Administration has given an emergency use authorization (EUA) for the therapy.

The agency’s move took many investigators by surprise. The EUA was announced at the White House the day after President Donald J. Trump accused the FDA of delaying approval of therapeutics to hurt his re-election chances.

In a memo describing the decision, the FDA cited data from some controlled and uncontrolled studies and, primarily, data from an open-label expanded-access protocol overseen by the Mayo Clinic.

At the White House, FDA Commissioner Stephen Hahn, MD, said that plasma had been found to save the lives of 35 out of every 100 who were treated. That figure was later found to have been erroneous, and many experts pointed out that Hahn had conflated an absolute risk reduction with a relative reduction. After a firestorm of criticism, Hahn issued an apology.

“The criticism is entirely justified,” he tweeted. “What I should have said better is that the data show a relative risk reduction not an absolute risk reduction.”

About 15 randomized controlled trials – out of 54 total studies involving convalescent plasma – are underway in the United States, according to ClinicalTrials.gov. The FDA’s Aug. 23 emergency authorization gave clinicians wide leeway to employ convalescent plasma in patients hospitalized with COVID-19.

The agency noted, however, that “adequate and well-controlled randomized trials remain necessary for a definitive demonstration of COVID-19 convalescent plasma efficacy and to determine the optimal product attributes and appropriate patient populations for its use.”

But it’s not clear that people with COVID-19, especially those who are severely ill and hospitalized, will choose to enlist in a clinical trial – where they could receive a placebo – when they instead could get plasma.

“I’ve been asked repeatedly whether the EUA will affect our ability to recruit people into our hospitalized patient trial,” said Liise-anne Pirofski, MD, FIDSA, chief of the department of medicine, infectious diseases division at Albert Einstein College of Medicine and Montefiore Medical Center in the Bronx, New York. “I do not know,” she said, on a call with reporters organized by the Infectious Diseases Society of America.

“But,” she said, “I do know that the trial will continue and that we will discuss the evidence that we have with our patients and give them all that we can to help them weigh the evidence and make up their minds.”

Pirofski said the study being conducted at Montefiore and four other sites has since late April enrolled 190 patients out of a hoped-for 300.

When the study – which compares convalescent plasma to saline in hospitalized patients – was first designed, “there was not any funding for our trial and honestly not a whole lot of interest,” Pirofski told reporters. Individual donors helped support the initial rollout in late April and the trial quickly enrolled 150 patients as the pandemic peaked in the New York City area.

The National Institutes of Health has since given funding, which allowed the study to expand to New York University, Yale University, the University of Miami, and the University of Texas at Houston.
 

Hopeful, but a long way to go

Shmuel Shoham, MD, FIDSA, associate director of the transplant and oncology infectious diseases center at Johns Hopkins University School of Medicine in Baltimore, said that he’s hopeful that people will continue to enroll in his trial, which is seeking to determine if plasma can prevent COVID-19 in those who’ve been recently exposed.

“Volunteers joining the study is the only way that we’re going to get to know whether this stuff works for prevention and treatment,” Shoham said on the call. He urged physicians and other healthcare workers to talk with patients about considering trial participation.

Shoham’s study is being conducted at 30 US sites and one at the Navajo Nation. It has enrolled 25 out of a hoped-for 500 participants. “We have a long way to go,” said Shoham.

Another Hopkins study to determine whether plasma is helpful in shortening illness in nonhospitalized patients, which is being conducted at the same 31 sites, has enrolled 50 out of 600.

Shoham said recruiting patients with COVID for any study had proven to be difficult. “The vast majority of people that have coronavirus do not come to centers that do clinical trials or interventional trials,” he said, adding that, in addition, most of those “who have coronavirus don’t want to be in a trial. They just want to have coronavirus and get it over with.”

But it’s important to understand how to conduct trials in a pandemic – in part to get answers quickly, he said. Researchers have been looking at convalescent plasma for months, said Shoham. “Why don’t we have the randomized clinical trial data that we want?”

Pirofski noted that trials have also been hobbled in part by “the shifting areas of the pandemic.” Fewer cases make for fewer potential plasma donors.

Both Shoham and Pirofski also said that more needed to be done to encourage plasma donors to participate.

The US Department of Health & Human Services clarified in August that hospitals, physicians, health plans, and other health care workers could contact individuals who had recovered from COVID-19 without violating the HIPAA privacy rule.

Pirofski said she believes that trial investigators know it is legal to reach out to patients. But, she said, “it probably could be better known.”
 

This article first appeared on Medscape.com.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

The risk of depression is elevated in patients with cardiovascular diseases, but several specific antihypertensive therapies are associated with a reduced risk, and none appear to increase the risk, according to a population-based study that evaluated 10 years of data in nearly 4 million subjects.

“As the first study on individual antihypertensives and risk of depression, we found a decreased risk of depression with nine drugs,” reported a collaborative group of investigators from multiple institutions in Denmark where the study was undertaken.

In a study period spanning from 2005 to 2015, risk of a diagnosis of depression was evaluated in patients taking any of 41 antihypertensive therapies in four major categories. These were identified as angiotensin agents (ACE inhibitors or angiotensin II receptor blockers), calcium antagonists, beta-blockers, and diuretics.

Within these groups, agents associated with a reduced risk of depression were: two angiotensin agents, enalapril and ramipril; three calcium antagonists, amlodipine, verapamil, and verapamil combinations; and four beta-blockers, propranolol, atenolol, bisoprolol, and carvedilol. The remaining drugs in these classes and diuretics were not associated with a reduced risk of depression. However, no antihypertensive agent was linked to an increased risk of depression.

All people living in Denmark are assigned a unique personal identification number that permits health information to be tracked across multiple registers. In this study, information was linked for several registries, including the Danish Medical Register on Vital Statistics, the Medicinal Product Statistics, and the Danish Psychiatric Central Register.

Data from a total of 3.75 million patients exposed to antihypertensive therapy during the study period were evaluated. Roughly 1 million of them were exposed to angiotensin drugs and slightly more than a million were exposed to diuretics. For calcium antagonists or beta-blockers, the numbers were approximately 835,000 and 775,000, respectively.

After adjustment for such factors as concomitant somatic diagnoses, sex, age, and employment status, the hazard ratios for depression among drugs associated with protection identified a risk reduction of 10%-25% in most cases when those who had been given 6-10 prescriptions or more than 10 prescriptions were compared with those who received 2 or fewer.

At the level of 10 or more prescriptions, for example, the risk reductions were 17% for ramipril (HR, 0.83; 95% CI, 0.78-0.89), 8% for enalapril (HR, 0.92; 95% CI, 0.88-0.96), 18% for amlodipine (HR, 0.82; 95% CI, 0.79-0.86), 15% for verapamil (HR, 0.85; 95% CI, 0.79-0.83), 28% for propranolol (HR, 0.72; 95% CI, 0.67-0.77), 20% for atenolol (HR, 0.80; 95% CI, 0.74-0.86), 25% for bisoprolol (HR, 0.75; 95% CI, 0.67-0.84), and 16% for carvedilol (HR, 0.84; 95% CI, 0.75-0.95).

For verapamil combinations, the risk reduction was 67% (HR, 0.33; 95% CI, 0.17-0.63), but the investigators cautioned that only 130 individuals were exposed to verapamil combinations, limiting the reliability of this analysis.
 

Interpreting the findings

A study hypothesis, the observed protective effect against depression, was expected for angiotensin drugs and calcium-channel blockers, but not for beta-blockers, according to the investigators.

“The renin-angiotensin systems is one of the pathways known to modulate inflammation in the central nervous system and seems involved in the regulation of the stress response. Angiotensin agents may also exert anti-inflammatory effects,” the investigators explained. “Dysregulation of intracellular calcium is evident in depression, including receptor-regulated calcium signaling.”

In contrast, beta-blockers have been associated with increased risk of depression in some but not all studies, according to the investigators. They maintained that some clinicians avoid these agents in patients with a history of mood disorders.

In attempting to account for the variability within drug classes regarding protection and lack of protection against depression, the investigators speculated that differences in pharmacologic properties, such as relative lipophilicity or anti-inflammatory effect, might be important.

Despite the large amount of data, William B. White, MD, professor emeritus at the Calhoun Cardiology Center, University of Connecticut, Farmington, is not convinced.

“In observational studies, even those with very large samples sizes, bias and confounding are hard to extricate with controls and propensity-score matching,” Dr. White said. From his perspective, the protective effects of some but not all drugs within a class “give one the impression that the findings are likely random.”

A member of the editorial board of the journal in which this study appeared, Dr. White said he was not involved in the review of the manuscript. Ultimately, he believed that the results are difficult to interpret.

“For example, there is no plausible rationale for why 2 of the 16 ACE inhibitors or angiotensin II receptor blockers or 4 of the 15 beta-blockers or 3 of the 10 calcium-channel blockers would reduce depression while the others in the class would have no effect,” he said.

Despite the investigators’ conclusion that these data should drive drug choice for patients at risk of depression, “I would say the results of this analysis would not lead me to alter clinical practice,” Dr. White added.

According to the principal investigator of the study, Lars Vedel Kessing, MD, DSc, professor of psychiatry at the University of Copenhagen, many variables affect choice of antihypertensive drug. However, the depression risk is elevated in patients with cardiovascular or cerebrovascular disease and hypertension.

When risk of a mood disorder is a concern, use of one of the nine drugs associated with protection from depression should be considered, “especially in patients at increased risk of developing depression, including patients with prior depression or anxiety and patients with a family history of depression,” he and his coinvestigators concluded.

However, Dr. Kessing said in an interview that the data do not help with individual treatment choices. “We do not compare different antihypertensives against each other due to the risk of confounding by indications, so, no, it is not reasonable to consider relative risk among specific agents.”

The authors reported no potential conflicts of interest involving this topic.

SOURCE: Kessing LV et al. Hypertension. 2020 Aug 24. doi: 10.1161/HYPERTENSIONAHA.120.15605.

Jerome Antone said he is one of the lucky ones.

Courtesy of Christopher Smith for KHN

After becoming ill with COVID-19, Mr. Antone was hospitalized only 65 miles away from his small Alabama town. He is the mayor of Georgiana – population 1,700.

“It hit our rural community so rabid,” Mr. Antone said. The town’s hospital closed last year. If hospitals in nearby communities don’t have beds available, “you may have to go 4 or 5 hours away.”

As COVID-19 continues to spread, an increasing number of rural communities find themselves without their hospital or on the brink of losing already cash-strapped facilities.

Eighteen rural hospitals closed last year and the first 3 months of 2020 were “really big months,” said Mark Holmes, PhD, director of the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. Many of the losses are in Southern states like Florida and Texas. More than 170 rural hospitals have closed nationwide since 2005, according to data collected by the Sheps Center.

It’s a dangerous scenario. “We know that a closure leads to higher mortality pretty quickly” among the populations served, said Dr. Holmes, who is also a professor at UNC Gillings School of Global Public Health. “That’s pretty clear.”

One 2019 study found that death rates in the surrounding communities increase nearly 6% after a rural hospital closes – and that’s when there’s not a pandemic.

Add to that what is known about the coronavirus: People who are obese or live with diabetes, hypertension, asthma, and other underlying health issues are more susceptible to COVID-19. Rural areas tend to have higher rates of these conditions. And rural residents are more likely to be older, sicker and poorer than those in urban areas. All this leaves rural communities particularly vulnerable to the coronavirus.

Congress approved billions in federal relief funds for health care providers. Initially, federal officials based what a hospital would get on its Medicare payments, but by late April they heeded criticism and carved out funds for rural hospitals and COVID-19 hot spots. Rural hospitals leapt at the chance to shore up already-negative budgets and prepare for the pandemic.

The funds “helped rural hospitals with the immediate storm,” said Don Williamson, MD, president of the Alabama Hospital Association. Nearly 80% of Alabama’s rural hospitals began the year with negative balance sheets and about 8 days’ worth of cash on hand.

Before the pandemic hit this year, hundreds of rural hospitals “were just trying to keep their doors open,” said Maggie Elehwany, vice president of government affairs with the National Rural Health Association. Then an estimated 70% of their income stopped as patients avoided the emergency room, doctor’s appointments, and elective surgeries.

“It was devastating,” Ms. Elehwany said.

Paul Taylor, chief executive of a 25-bed critical-access hospital and outpatient clinics in northwestern Arkansas, accepted millions in grants and loan money Congress approved this spring, largely through the CARES (Coronavirus Aid, Relief, and Economic Security) Act.

“For us, this was survival money and we spent it already,” Mr. Taylor said. With those funds, Ozarks Community Hospital increased surge capacity, expanding from 25 beds to 50 beds, adding negative pressure rooms and buying six ventilators. Taylor also ramped up COVID-19 testing at his hospital and clinics, located near some meat-processing plants.

Throughout June and July, Ozarks tested 1,000 patients a day and reported a 20% positive rate. The rate dropped to 16.9% in late July. But patients continue to avoid routine care.

Mr. Taylor said revenue is still constrained and he does not know how he will pay back $8 million that he borrowed from Medicare. The program allowed hospitals to borrow against future payments from the federal government, but stipulated that repayment would begin within 120 days.

For Mr. Taylor, this seems impossible. Medicare makes up 40% of Ozarks’ income. And he has to pay the loan back before he gets any more payments from Medicare. He’s hoping to refinance the hospital’s mortgage.

“If I get no relief and they take the money ... we won’t still be open,” Mr. Taylor said. Ozarks provides 625 jobs and serves an area with a population of about 75,000.

There are 1,300 small critical-access hospitals like Ozarks in rural America, and of those, 859 took advantage of the Medicare loans, sending about $3.1 billion into the local communities. But many rural communities have not yet experienced a surge in coronavirus cases – national leaders fear it will come as part of a new phase.

“There are pockets of rural America who say, ‘We haven’t seen a single COVID patient yet and we do not believe it’s real,’ ” Mr. Taylor said. “They will get hit sooner or later.”

Across the country, the reduced patient numbers and increased spending required to fight and prepare for the coronavirus was “like a knife cutting into a hospital’s blood supply,” said Ge Bai, PhD, associate professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Dr. Bai said the way the federal government reimbursed small rural hospitals through federal programs like Medicare before the pandemic was faulty and inefficient. “They are too weak to survive,” she said.

In rural Texas, about 2 hours from Dallas, Titus Regional Medical Center chief executive officer Terry Scoggin cut staff and furloughed workers even as his rural hospital faced down the pandemic. Titus Regional lost about $4 million last fiscal year and broke even each of the three years before that.

Mr. Scoggin said he did not cut from his clinical staff, though. Titus is now facing its second surge of the virus in the community. “The last 7 days, we’ve been testing 30% positive,” he said, including the case of his father, who contracted it at a nursing home and survived.

“It’s personal and this is real,” Mr. Scoggin said. “You know the people who are infected. You know the people who are passing away.”

Of his roughly 700 employees, 48 have tested positive for the virus and 1 has died. They are short on testing kits, medication, and supplies.

“Right now the staff is strained,” Mr. Scoggin said. “I’ve been blown away by their selflessness and unbelievable spirit. We’re resilient, we’re nimble, and we will make it. We don’t have a choice.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Jerome Antone said he is one of the lucky ones.

Courtesy of Christopher Smith for KHN

After becoming ill with COVID-19, Mr. Antone was hospitalized only 65 miles away from his small Alabama town. He is the mayor of Georgiana – population 1,700.

“It hit our rural community so rabid,” Mr. Antone said. The town’s hospital closed last year. If hospitals in nearby communities don’t have beds available, “you may have to go 4 or 5 hours away.”

As COVID-19 continues to spread, an increasing number of rural communities find themselves without their hospital or on the brink of losing already cash-strapped facilities.

Eighteen rural hospitals closed last year and the first 3 months of 2020 were “really big months,” said Mark Holmes, PhD, director of the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. Many of the losses are in Southern states like Florida and Texas. More than 170 rural hospitals have closed nationwide since 2005, according to data collected by the Sheps Center.

It’s a dangerous scenario. “We know that a closure leads to higher mortality pretty quickly” among the populations served, said Dr. Holmes, who is also a professor at UNC Gillings School of Global Public Health. “That’s pretty clear.”

One 2019 study found that death rates in the surrounding communities increase nearly 6% after a rural hospital closes – and that’s when there’s not a pandemic.

Add to that what is known about the coronavirus: People who are obese or live with diabetes, hypertension, asthma, and other underlying health issues are more susceptible to COVID-19. Rural areas tend to have higher rates of these conditions. And rural residents are more likely to be older, sicker and poorer than those in urban areas. All this leaves rural communities particularly vulnerable to the coronavirus.

Congress approved billions in federal relief funds for health care providers. Initially, federal officials based what a hospital would get on its Medicare payments, but by late April they heeded criticism and carved out funds for rural hospitals and COVID-19 hot spots. Rural hospitals leapt at the chance to shore up already-negative budgets and prepare for the pandemic.

The funds “helped rural hospitals with the immediate storm,” said Don Williamson, MD, president of the Alabama Hospital Association. Nearly 80% of Alabama’s rural hospitals began the year with negative balance sheets and about 8 days’ worth of cash on hand.

Before the pandemic hit this year, hundreds of rural hospitals “were just trying to keep their doors open,” said Maggie Elehwany, vice president of government affairs with the National Rural Health Association. Then an estimated 70% of their income stopped as patients avoided the emergency room, doctor’s appointments, and elective surgeries.

“It was devastating,” Ms. Elehwany said.

Paul Taylor, chief executive of a 25-bed critical-access hospital and outpatient clinics in northwestern Arkansas, accepted millions in grants and loan money Congress approved this spring, largely through the CARES (Coronavirus Aid, Relief, and Economic Security) Act.

“For us, this was survival money and we spent it already,” Mr. Taylor said. With those funds, Ozarks Community Hospital increased surge capacity, expanding from 25 beds to 50 beds, adding negative pressure rooms and buying six ventilators. Taylor also ramped up COVID-19 testing at his hospital and clinics, located near some meat-processing plants.

Throughout June and July, Ozarks tested 1,000 patients a day and reported a 20% positive rate. The rate dropped to 16.9% in late July. But patients continue to avoid routine care.

Mr. Taylor said revenue is still constrained and he does not know how he will pay back $8 million that he borrowed from Medicare. The program allowed hospitals to borrow against future payments from the federal government, but stipulated that repayment would begin within 120 days.

For Mr. Taylor, this seems impossible. Medicare makes up 40% of Ozarks’ income. And he has to pay the loan back before he gets any more payments from Medicare. He’s hoping to refinance the hospital’s mortgage.

“If I get no relief and they take the money ... we won’t still be open,” Mr. Taylor said. Ozarks provides 625 jobs and serves an area with a population of about 75,000.

There are 1,300 small critical-access hospitals like Ozarks in rural America, and of those, 859 took advantage of the Medicare loans, sending about $3.1 billion into the local communities. But many rural communities have not yet experienced a surge in coronavirus cases – national leaders fear it will come as part of a new phase.

“There are pockets of rural America who say, ‘We haven’t seen a single COVID patient yet and we do not believe it’s real,’ ” Mr. Taylor said. “They will get hit sooner or later.”

Across the country, the reduced patient numbers and increased spending required to fight and prepare for the coronavirus was “like a knife cutting into a hospital’s blood supply,” said Ge Bai, PhD, associate professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Dr. Bai said the way the federal government reimbursed small rural hospitals through federal programs like Medicare before the pandemic was faulty and inefficient. “They are too weak to survive,” she said.

In rural Texas, about 2 hours from Dallas, Titus Regional Medical Center chief executive officer Terry Scoggin cut staff and furloughed workers even as his rural hospital faced down the pandemic. Titus Regional lost about $4 million last fiscal year and broke even each of the three years before that.

Mr. Scoggin said he did not cut from his clinical staff, though. Titus is now facing its second surge of the virus in the community. “The last 7 days, we’ve been testing 30% positive,” he said, including the case of his father, who contracted it at a nursing home and survived.

“It’s personal and this is real,” Mr. Scoggin said. “You know the people who are infected. You know the people who are passing away.”

Of his roughly 700 employees, 48 have tested positive for the virus and 1 has died. They are short on testing kits, medication, and supplies.

“Right now the staff is strained,” Mr. Scoggin said. “I’ve been blown away by their selflessness and unbelievable spirit. We’re resilient, we’re nimble, and we will make it. We don’t have a choice.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

Jerome Antone said he is one of the lucky ones.

Courtesy of Christopher Smith for KHN

After becoming ill with COVID-19, Mr. Antone was hospitalized only 65 miles away from his small Alabama town. He is the mayor of Georgiana – population 1,700.

“It hit our rural community so rabid,” Mr. Antone said. The town’s hospital closed last year. If hospitals in nearby communities don’t have beds available, “you may have to go 4 or 5 hours away.”

As COVID-19 continues to spread, an increasing number of rural communities find themselves without their hospital or on the brink of losing already cash-strapped facilities.

Eighteen rural hospitals closed last year and the first 3 months of 2020 were “really big months,” said Mark Holmes, PhD, director of the Cecil G. Sheps Center for Health Services Research at the University of North Carolina at Chapel Hill. Many of the losses are in Southern states like Florida and Texas. More than 170 rural hospitals have closed nationwide since 2005, according to data collected by the Sheps Center.

It’s a dangerous scenario. “We know that a closure leads to higher mortality pretty quickly” among the populations served, said Dr. Holmes, who is also a professor at UNC Gillings School of Global Public Health. “That’s pretty clear.”

One 2019 study found that death rates in the surrounding communities increase nearly 6% after a rural hospital closes – and that’s when there’s not a pandemic.

Add to that what is known about the coronavirus: People who are obese or live with diabetes, hypertension, asthma, and other underlying health issues are more susceptible to COVID-19. Rural areas tend to have higher rates of these conditions. And rural residents are more likely to be older, sicker and poorer than those in urban areas. All this leaves rural communities particularly vulnerable to the coronavirus.

Congress approved billions in federal relief funds for health care providers. Initially, federal officials based what a hospital would get on its Medicare payments, but by late April they heeded criticism and carved out funds for rural hospitals and COVID-19 hot spots. Rural hospitals leapt at the chance to shore up already-negative budgets and prepare for the pandemic.

The funds “helped rural hospitals with the immediate storm,” said Don Williamson, MD, president of the Alabama Hospital Association. Nearly 80% of Alabama’s rural hospitals began the year with negative balance sheets and about 8 days’ worth of cash on hand.

Before the pandemic hit this year, hundreds of rural hospitals “were just trying to keep their doors open,” said Maggie Elehwany, vice president of government affairs with the National Rural Health Association. Then an estimated 70% of their income stopped as patients avoided the emergency room, doctor’s appointments, and elective surgeries.

“It was devastating,” Ms. Elehwany said.

Paul Taylor, chief executive of a 25-bed critical-access hospital and outpatient clinics in northwestern Arkansas, accepted millions in grants and loan money Congress approved this spring, largely through the CARES (Coronavirus Aid, Relief, and Economic Security) Act.

“For us, this was survival money and we spent it already,” Mr. Taylor said. With those funds, Ozarks Community Hospital increased surge capacity, expanding from 25 beds to 50 beds, adding negative pressure rooms and buying six ventilators. Taylor also ramped up COVID-19 testing at his hospital and clinics, located near some meat-processing plants.

Throughout June and July, Ozarks tested 1,000 patients a day and reported a 20% positive rate. The rate dropped to 16.9% in late July. But patients continue to avoid routine care.

Mr. Taylor said revenue is still constrained and he does not know how he will pay back $8 million that he borrowed from Medicare. The program allowed hospitals to borrow against future payments from the federal government, but stipulated that repayment would begin within 120 days.

For Mr. Taylor, this seems impossible. Medicare makes up 40% of Ozarks’ income. And he has to pay the loan back before he gets any more payments from Medicare. He’s hoping to refinance the hospital’s mortgage.

“If I get no relief and they take the money ... we won’t still be open,” Mr. Taylor said. Ozarks provides 625 jobs and serves an area with a population of about 75,000.

There are 1,300 small critical-access hospitals like Ozarks in rural America, and of those, 859 took advantage of the Medicare loans, sending about $3.1 billion into the local communities. But many rural communities have not yet experienced a surge in coronavirus cases – national leaders fear it will come as part of a new phase.

“There are pockets of rural America who say, ‘We haven’t seen a single COVID patient yet and we do not believe it’s real,’ ” Mr. Taylor said. “They will get hit sooner or later.”

Across the country, the reduced patient numbers and increased spending required to fight and prepare for the coronavirus was “like a knife cutting into a hospital’s blood supply,” said Ge Bai, PhD, associate professor of health policy and management at the Johns Hopkins Bloomberg School of Public Health in Baltimore.

Dr. Bai said the way the federal government reimbursed small rural hospitals through federal programs like Medicare before the pandemic was faulty and inefficient. “They are too weak to survive,” she said.

In rural Texas, about 2 hours from Dallas, Titus Regional Medical Center chief executive officer Terry Scoggin cut staff and furloughed workers even as his rural hospital faced down the pandemic. Titus Regional lost about $4 million last fiscal year and broke even each of the three years before that.

Mr. Scoggin said he did not cut from his clinical staff, though. Titus is now facing its second surge of the virus in the community. “The last 7 days, we’ve been testing 30% positive,” he said, including the case of his father, who contracted it at a nursing home and survived.

“It’s personal and this is real,” Mr. Scoggin said. “You know the people who are infected. You know the people who are passing away.”

Of his roughly 700 employees, 48 have tested positive for the virus and 1 has died. They are short on testing kits, medication, and supplies.

“Right now the staff is strained,” Mr. Scoggin said. “I’ve been blown away by their selflessness and unbelievable spirit. We’re resilient, we’re nimble, and we will make it. We don’t have a choice.”

Kaiser Health News is a nonprofit news service covering health issues. It is an editorially independent program of the Kaiser Family Foundation, which is not affiliated with Kaiser Permanente.

The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.

Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.

“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”

With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.

Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”

That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.

Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
 

Flu vaccine ‘extra important’

The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.

The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.

But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
 

Risks of coinfection

About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.

“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”

Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
 

Distinguishing COVID-19 from flu

Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.

Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.

“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.

But even after that, symptoms can be difficult to distinguish.

“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”

But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”

Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.

Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.

In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”

Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”

The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”

That may be somewhat welcome as flu season arrives.

The physicians interviewed have no relevant disclosures.

The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.

Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.

“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”

With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.

Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”

That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.

Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
 

Flu vaccine ‘extra important’

The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.

The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.

But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
 

Risks of coinfection

About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.

“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”

Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
 

Distinguishing COVID-19 from flu

Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.

Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.

“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.

But even after that, symptoms can be difficult to distinguish.

“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”

But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”

Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.

Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.

In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”

Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”

The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”

That may be somewhat welcome as flu season arrives.

The physicians interviewed have no relevant disclosures.

The medical community is about to find out how prepared it is for the double whammy of influenza and COVID-19 that has been predicted for the fall of 2020. The complexities of diagnosis, management of vulnerable patients, and overflowing medical centers that have made the COVID-19 crisis so brutal may all be exacerbated by the arrival of seasonal influenza.

Lewis Jay Kaplan, MD, FCCP, a critical care surgeon at the University of Pennsylvania, Philadelphia, has seen his share of critically ill COVID-19 patients in the surgical ICU that he oversees. He’s approaching the upcoming flu season, poised to collide with the ongoing COVID-19 pandemic, ready to listen to each patient’s story to distinguish one from the other and determine treatment.

“The patients that have underlying comorbidities all have a story, and it’s up to you to figure out which chapter you’re in and how far along you happen to be,” he said. “It’s a very interesting approach to care, medical storytelling.”

With flu season closing in, pulmonologists are ruminating about how they’ll distinguish symptoms of COVID-19 and traditional influenza and how they’ll manage the most vulnerable patients, namely those with underlying respiratory disease and children. Influenza kills 12,000-61,000 people a year, according to the Centers for Disease Control, and results in 140,000-810,00 hospitalizations. Having a flu season in the midst of a pandemic of a disease with multiple overlapping symptoms threatens to overwhelm practitioners, hospitals, and the health system.

Dr. Kaplan said each patient’s story can point to the correct clinical approach. “Instead of just sharing data when you are on rounds, you’re really telling someone’s story.” It arises from a series of questions about how the disease has impacted them, specifics of their presentation, how their signs and symptoms differ from the usual, and how they responded to treatment. “It also helps you to then take what you’re doing, which can seem very, very complicated to individuals who are not medically sophisticated, and then help them to understand why you’re doing what you’re doing at this point.”

That can help get through to a patient with respiratory disease who insists he or she has or doesn’t have COVID-19 rather than the flu. “They form a different group that brings with them different fears and concerns, and you have to help them navigate that, too: all of this data and your decision-making around testing and admissions, and what you can omit doing and what you must do help them to navigate their own story,” Dr. Kaplan said.

Benjamin D. Singer, MD, a pulmonologist at Northwestern University, Chicago, authored an editorial in Science Advances that addressed four factors that will determine the scope of flu spread in the upcoming season: rate of transmission; vaccination rates; coinfection rates; and health disparities in minority populations, which are prone to higher rates of flu as well as COVID-19.
 

Flu vaccine ‘extra important’

The convergence of COVID-19 and influenza has the potential to overwhelm the health system, said Daniel A. Solomon, MD, of Brigham and Women’s in Boston. He coauthored a JAMA Insights clinical update on flu season during the COVID-19 pandemic that lists distinguishing and overlapping signs and symptoms of the two diseases.

The flu vaccine, he said, is “extra important this year,” especially in patients with existing respiratory disease, but COVID-19 has thrown up barriers to vaccination. Telemedicine has supplanted office visits. “People may miss that easy-touch opportunity to get the flu vaccine, so we have to be creative about making the flu vaccine highly accessible, maybe in nontraditional ways,” Dr. Solomon said. Some ideas he offered are pop-up vaccine fairs at schools and churches.

But just as COVID-19 may hinder flu vaccines, it may also be helping to mitigate flu transmission. “The interesting thing about transmission of the flu is that it’s transmitted the same way COVID is, so if we actually know how to decrease transmission of COVID, which we do – we’ve done it – we can actually decrease transmission of influenza as well,” Dr. Solomon said. Studies out of Hong Kong and Japan have reported a reduction in influenza cases during COVID-19 outbreaks in those places (Lancet Public Health. 2020;5:e279-88; JAMA. 2020;323:1969-71).
 

Risks of coinfection

About one in four COVID-19 patients have been diagnosed with an additional respiratory infection, including influenza (JAMA. 2020:323:2085-6). Pulmonologists must keep that in mind when managing COVID-19 suspects, said Dr. Singer.

“While it is true that most of the time COVID-19 travels alone, we have numerous examples in the literature and in our own experience that COVID-19 is accompanied by either another virus or another bacterial infection, including influenza,” Dr. Singer said. “The distinction is important. One is just for diagnostic reasons and public reporting reasons, but also because flu and COVID-19 have different requirements for how you care for patients in terms of the health system.”

Clinical suspicion for coinfection should remain high if the community spread of both COVID-19 and influenza is high, said Megan Conroy, MD, chief pulmonary and critical care fellow at Ohio State University, Columbus. “As the coronavirus first took hold in the United States in March 2020, we were at the tail end of influenza season, so it’s hard to predict what the upcoming influenza season will really look like with regards to coinfection.”
 

Distinguishing COVID-19 from flu

Multiple signs and symptoms between COVID-19 and the flu overlap. They include fever, chills, headache, myalgia, cough, and fatigue. Nasal congestion and sore throat are characteristic of the flu; shortness of breath and loss of the sense of smell have been widely reported in COVID-19. “While many upper respiratory infections can result in loss of smell, this may be more prevalent in COVID-19,” Dr. Conroy said. Other symptoms unique to COVID-19 are GI symptoms such as diarrhea and skin rashes such as acral ischemia.

Testing, however, is the cornerstone of the differential diagnosis. “You can’t confidently distinguish between them on symptoms alone,” Dr. Conroy added.

“I think the challenge we’ll face as clinicians, is caring for people with nonspecific symptoms of a respiratory viral illness, especially in the early phase of the illness,” said Dr. Solomon.

But even after that, symptoms can be difficult to distinguish.

“Later in the illness, COVID is more associated with a hypercoagulable state,” he said. “It is more associated with viral pneumonia on chest imaging, like the diffuse ground-glass infiltrates that we’ve all gotten used to seeing – but flu can do both of those things as well. So, without a test, it’s impossible to distinguish between the two infections in the clinic.”

But testing can have its shortcomings when flu season clashes with the COVID-19 pandemic. “Getting the test is not the same as getting the test results,” Dr. Solomon added. “Though a lot of people can get a test, if it takes 7 or 8 days to get the test result back, the result is useless.”

Widespread, rapid testing also depends on having adequate supplies of viral media transport and swabs. “I think that this is what we should be focusing on now: scaling up access to rapid turnaround testing,” he said. Distinguishing between the two is also important to preserve hospital resources. COVID-19 has more rigorous standards than flu for personal protective equipment and isolation of patients within the hospital.

Having chronic lung disease isn’t necessarily a risk factor for contracting COVID-19 or the flu, or both, Dr. Solomon said. “It’s a risk factor for having severe disease.” Again, he noted that flu vaccines are still necessary in these patients, as well as patients of advanced age and underlying medical conditions such as heart disease, diabetes, and obesity.

In managing children, it’s important to keep in mind that they communicate differently about their illnesses than adults, said Dr. Kaplan. “They may not have the words to tell you the same kind of thing that the adult tells you.” That’s where family members can help to flesh out the history. “They may present with an initially much milder form, if you will, where they’re not as critical up front, but then that small proportion of them comes back with the multi-inflammatory syndrome and then they are profoundly ill.”

Younger people make up a larger share of COVID-19 patients now, compared with the initial wave that hit the Northeast in the spring, Dr. Kaplan said. “We don’t know if that’s because the virus is a little different or the people that are getting sick are a little bit different.”

The COVID-19 strain now emerging may be less virulent than the strain that hit in early spring, he said. “That doesn’t mean that there aren’t still profoundly critical ill people with COVID of many different age ranges, that is true, but there are a lot of people that we now see will test positive, but aren’t really as profoundly ill as when it first landed here in the United States.”

That may be somewhat welcome as flu season arrives.

The physicians interviewed have no relevant disclosures.

Children represented 9.3% of all U.S. COVID-19 cases as of Aug. 20, 2020 – an increase from 9.1% the previous week – but only 0.06% of all U.S. deaths reported, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.

Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.

Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.

There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.

The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.

The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.

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Children represented 9.3% of all U.S. COVID-19 cases as of Aug. 20, 2020 – an increase from 9.1% the previous week – but only 0.06% of all U.S. deaths reported, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.

Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.

Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.

There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.

The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.

The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.

[email protected]

Children represented 9.3% of all U.S. COVID-19 cases as of Aug. 20, 2020 – an increase from 9.1% the previous week – but only 0.06% of all U.S. deaths reported, according to a report from the American Academy of Pediatrics and the Children’s Hospital Association.

The cumulative number of pediatric cases reported up to that date was 442,785, or 9.3% of the total COVID-19 case load of more than 4.76 million among all ages. There have been only 92 pediatric deaths, however, which works out to just 0.06% of the 154,279 reported for all ages, the AAP and the CHA said Aug. 24 in their most recent update.

Child hospitalizations also were on the low side, representing 1.7% (4,062) of the cumulative total of 234,810 admissions among all ages as of Aug. 20, based on data from 21 states and New York City.

Nationally, the cumulative number of reported child cases is now up to 583 per 100,000 children, and that figure covers 49 states, Washington, D.C., Guam, New York City, and Puerto Rico.

There is some disagreement among the states, though, about the definition of “child.” Most states use an age range of 0-17, 0-18, or 0-19, but Florida and Utah go with a range of 0-14 years while South Carolina and Tennessee consider humans aged 0-20 years to be children. Other data limitations involve Texas, which has reported age distribution for only 8% of all cases, and New York, which is not reporting the age distribution of statewide cases, the AAP/CHA report noted.

The definition of child isn’t the only thing that varies between the states. The cumulative case rate for Tennessee, the highest in the country at 1,315 per 100,000 children, is 10 times that of Vermont, which is the lowest at 131 per 100,000, the AAP and CHA said. Vermont reports child COVID-19 cases using an age range of 0-19 years.

The other states with rates over 1,000 cases per 100,000 children are Arizona (1,300), which had the highest rate a week ago; South Carolina (1,214); Louisiana (1,127); Mississippi (1,120); and Nevada (1,068). Those with rates below 200 cases per 100,000 children are Maine (150), New Hampshire (175), and Hawaii (188), according to this week’s report.

[email protected]

SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.

It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.

The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.

“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.

There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.

“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
 

‘Concerning’ case report

“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.

“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.

The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.

SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.

Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.

Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.

Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.

Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.

Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.

“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.

“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.

Experts weigh in

Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.

“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.

Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”

“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.

He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.

“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.

This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.

This article first appeared on Medscape.com.

SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.

It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.

The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.

“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.

There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.

“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
 

‘Concerning’ case report

“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.

“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.

The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.

SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.

Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.

Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.

Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.

Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.

Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.

“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.

“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.

Experts weigh in

Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.

“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.

Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”

“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.

He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.

“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.

This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.

This article first appeared on Medscape.com.

SARS-CoV-2 has been found in cardiac tissue of a child from Brazil with multisystem inflammatory syndrome (MIS-C) related to COVID-19 who presented with myocarditis and died of heart failure.

It’s believed to be the first evidence of direct infection of heart muscle cells by the virus; viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.

The case was described in a report published online August 20 in The Lancet Child & Adolescent Health.

“The presence of the virus in various cell types of cardiac tissue, as evidenced by electron microscopy, shows that myocarditis in this case is likely a direct inflammatory response to the virus infection in the heart,” first author Marisa Dolhnikoff, MD, department of pathology, University of São Paulo, said in an interview.

There have been previous reports in adults with COVID-19 of both SARS-CoV-2 RNA by reverse transcription–polymerase chain reaction (RT-PCR) and viral particles by electron microscopy in cardiac tissue from endomyocardial specimens, the researchers noted. One of these reports, published in April by Tavazzi and colleagues, “detected viral particles in cardiac macrophages in an adult patient with acute cardiac injury associated with COVID-19; no viral particles were seen in cardiomyocytes or endothelial cells.

“Our case report is the first to our knowledge to document the presence of viral particles in the cardiac tissue of a child affected by MIS-C,” they added. “Moreover, viral particles were identified in different cell lineages of the heart, including cardiomyocytes, endothelial cells, mesenchymal cells, and inflammatory cells.”
 

‘Concerning’ case report

“This is a concerning report as it shows for the first time that the virus can actually invade the heart muscle cells themselves,” C. Michael Gibson, MD, CEO of the Baim Institute for Clinical Research in Boston, said in an interview.

“Previous reports of COVID-19 and the heart found that the virus was in the area outside the heart muscle cells. We do not know yet the relative contribution of the inflammatory cells invading the heart, the release of blood-borne inflammatory mediators, and the virus inside the heart muscle cells themselves to heart damage,” Dr. Gibson said.

The patient was a previously healthy 11-year-old girl of African descent with MIS-C related to COVID-19. She developed cardiac failure and died after 1 day in the hospital, despite aggressive treatment.

SARS-CoV-2 RNA was detected on a postmortem nasopharyngeal swab and in cardiac and pulmonary tissues by RT-PCR.

Postmortem ultrasound examination of the heart showed a “hyperechogenic and diffusely thickened endocardium (mean thickness, 10 mm), a thickened myocardium (18 mm thick in the left ventricle), and a small pericardial effusion,” Dr. Dolhnikoff and colleagues reported.

Histopathologic exam revealed myocarditis, pericarditis, and endocarditis characterized by infiltration of inflammatory cells. Inflammation was mainly interstitial and perivascular, associated with foci of cardiomyocyte necrosis and was mainly composed of CD68+ macrophages, a few CD45+ lymphocytes, and a few neutrophils and eosinophils.

Electron microscopy of cardiac tissue revealed spherical viral particles in shape and size consistent with the Coronaviridae family in the extracellular compartment and within cardiomyocytes, capillary endothelial cells, endocardium endothelial cells, macrophages, neutrophils, and fibroblasts.

Microthrombi in the pulmonary arterioles and renal glomerular capillaries were also seen at autopsy. SARS-CoV-2–associated pneumonia was mild.

Lymphoid depletion and signs of hemophagocytosis were observed in the spleen and lymph nodes. Acute tubular necrosis in the kidneys and hepatic centrilobular necrosis, secondary to shock, were also seen. Brain tissue showed microglial reactivity.

“Fortunately, MIS-C is a rare event and, although it can be severe and life threatening, most children recover,” Dr. Dolhnikoff commented.

“This case report comes at a time when the scientific community around the world calls attention to MIS-C and the need for it to be quickly recognized and treated by the pediatric community. Evidence of a direct relation between the virus and myocarditis confirms that MIS-C is one of the possible forms of presentation of COVID-19 and that the heart may be the target organ. It also alerts clinicians to possible cardiac sequelae in these children,” she added.

Experts weigh in

Scott Aydin, MD, medical director of pediatric cardiac intensive care, Mount Sinai Kravis Children’s Hospital in New York City, said that this case report is “unfortunately not all that surprising.

“Since the initial presentations of MIS-C several months ago, we have suspected mechanisms of direct and indirect injury to the myocardium. This important work is just the next step in further understanding the mechanisms of how COVID-19 creates havoc in the human body and the choices of possible therapies we have to treat children with COVID-19 and MIS-C,” said Dr. Aydin, who was not involved with the case report.

Anish Koka, MD, a cardiologist in private practice in Philadelphia, noted that, in these cases, endomyocardial biopsy is “rarely done because it is fairly invasive, but even when it has been done, the pathologic findings are of widespread inflammation rather than virus-induced cell necrosis.”

“While reports like this are sure to spawn viral tweets, it’s vital to understand that it’s not unusual to find widespread organ dissemination of virus in very sick patients. This does not mean that the virus is causing dysfunction of the organ it happens to be found in,” Dr. Koka said in an interview.

He noted that, in the case of the young girl who died, it took high PCR-cycle threshold values to isolate virus from the lung and heart samples.

“This means there was a low viral load in both organs, supporting the theory of SARS-CoV-2 as a potential trigger of a widespread inflammatory response that results in organ damage, rather than the virus itself infecting and destroying organs,” said Dr. Koka, who was also not associated with the case report.

This research had no specific funding. The authors declared no competing interests. Dr. Aydin disclosed no relevant financial relationships. Dr. Koka disclosed financial relationships with Boehringer Ingelheim and Jardiance.

This article first appeared on Medscape.com.

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

[email protected]

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

[email protected]

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

Among hospitalized COVID-19 patients, the use of famotidine was significantly associated with a reduction in death and either death or intubation. It also demonstrated lower levels of serum markers for severe disease.

The findings come from an observational study of 83 hospitalized patients that was published in the American Journal of Gastroenterology.

“The mechanism of exactly how famotidine works has yet to be proven,” lead study author Jeffrey F. Mather, MS, said in an interview. “There’s thought that it works directly on the virus, and there is thought that it works through inactivating certain proteases that are required for the virus infection, but I think the most interesting [hypothesis] is by Malone et al. “They’re looking at the blocking of the histamine-2 receptor causing a decrease in the amount of histamine. It’s all speculative, but it will be interesting if that gets worked out.”

In a study that largely mimicked that of an earlier, larger published observational study on the topic (doi: 10.1053/j.gastro.2020.05.053), Mr. Mather and colleagues retrospectively evaluated 878 patients who tested positive for SARS-CoV-2 and who required admission to Hartford (Conn.) Hospital between Feb. 24, 2020, and May 14, 2020. Patients were classified as receiving famotidine if they were treated with either oral or intravenous drug within 1 week of COVID-19 screening and/or hospital admission. Primary outcomes of interest were in-hospital death as recorded in the discharge of the patients, requirement for mechanical ventilation, and the composite of death or requirement for ventilation. Secondary outcomes of interest were several serum markers of disease activity including white blood cell count, lymphocyte count, and eosinophil count.

Famotidine was administered orally in 83% of the patients and intravenously in the remaining 17%. Mr. Mather, director of data management in the division of research management at Hartford Hospital, and his colleagues reported that 83 of the 878 patients studied (9.5%) received famotidine. Compared with patients not treated with famotidine, those who received the drug were slightly younger (a mean of 64 vs. 68 years, respectively; P = .021); otherwise, there were no differences between the two groups in baseline demographics or in preexisting comorbidities.

The use of famotidine was associated with a decreased risk of in-hospital mortality (odds ratio, 0.37; P = .021) as well as combined death or intubation (OR, 0.47; P = .040). The outcomes were similar when the researchers performed propensity score matching to adjust for age differences between groups.

In addition, the use of famotidine was associated with lower levels of serum markers for severe disease including lower median peak C-reactive protein levels (9.4 vs. 12.7 mg/dL; P =. 002), lower median procalcitonin levels (0.16 vs. 0.30 ng/mL; P = .004), and a nonsignificant trend to lower median mean ferritin levels (797.5 vs. 964 ng/mL; P = .076).

Logistic regression analysis revealed that use of famotidine was an independent predictor of both lower mortality and combined death/intubation. In addition, predictors of both adverse outcomes included older age, a body mass index of greater than 30 kg/m², chronic kidney disease, the national early warning score, and a higher neutrophil-lymphocyte ratio.

“This is an important stepping stone, but until we have a randomized, controlled trial, we really can’t speak about causation; we can only speak about association, and that’s okay,” Brennan Spiegel, MD, MSHS, director of health services research at Cedars-Sinai, Los Angeles, who was not affiliated with the study, said in an interview. “There’s nothing wrong with association because finding associations can raise important hypotheses that can then be tested in prospective randomized trials, for example.”

In July 2020, Dr. Spiegel and his colleagues published a separate paper looking at proton pump inhibitors and the risk of COVID-19. “In that study we did look at H₂ blockers, and we did find that they were slightly associated with a reduction in COVID-19,” he said. “It was a small effect, but it was a benefit. When we see consistency among studies, it’s a signal in the noise we can try and follow and see if there is something more to it.”

Mr. Mather acknowledged certain limitations of the study, including the fact that patients who did and did not receive famotidine were propensity-matched for age. “The risk factors that others have shown for adverse events are equivalent in the groups, but anytime you do a retrospective study like this there is the potential for underlying factors that may play a role in the outcomes that you’re not considering,” Mr. Mather said. “That’s why the gold standard is the randomized trial, to wash those effects out. There’s only an association here, and it supports the need for a randomized trial.”

Famotidine is currently being tested in a double-blind randomized clinical trial in combination with either hydroxychloroquine or remdesivir (NCT 04370262).

“It’s fascinating because famotidine is a safe medicine,” added Dr. Spiegel, who is also co–editor in chief of the American Journal of Gastroenterology. “There are very few side effects; it’s something we’ve been using for decades.”

Mr. Mather and his colleagues reported having no financial disclosures. Dr. Spiegel disclosed that he has served on advisory boards for Allergan, Alnylam Pharmaceuticals, Arena Pharmaceuticals, Ironwood Pharmaceuticals, Salix Pharmaceuticals, Synergy Pharmaceuticals, and Takeda Pharmaceuticals.

[email protected]

SOURCE: Mather J et al. 2020 Aug 14. Am J Gastroenterol.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.

The US Food and Drug Administration has approved phase one clinical trials for a synthetic cannabinoid drug designed to treat acute respiratory distress syndrome (ARDS), a life-threatening lung condition which may occur in severe cases of the novel coronavirus, Forbes reported.

ARDS can be triggered by over-creation of cytokines, proteins which tell the body to produce more inflammation, Forbes said.

The drug going to clinical trials, ARDS-003, would “dampen the cytokine release” and prevent development of ARDS, Tetra Bio-Pharma company CEO and chief regulatory officer Guy Chamberland, MD, said in a news release.

Consequences of ARDS include scarring of the lungs and organ injury caused by the decrease in blood to the tissue, the release said.

“The FDA repeatedly stated that they want clinical trials for COVID-19 to begin as soon as possible, as long as they meet regulatory requirements,” the news release said. “The medical community is in urgent need of drugs that can reduce the strength and duration of the severe inflammation. It is anticipated that this type of new drug would favorably impact health care and possibly reduce the negative health outcomes post infection.”

ARDS-003 works by binding to CB2 receptors, one of two main receptors in the endocannabinoid system which modulate inflammation and cytokine activity, Forbes said. CB2 receptors don’t bring on a psychoactive high.

Phase one clinical trials would begin enrolling participants in December to determine if the drug is safe, Chamberland said, according to Forbes.

If phase one is successful, phase two would test the drug on a larger group in the second quarter of 2021 to assess safety and tolerability for people who have COVID-19. 

If phase two is successful, the company may seek emergency authorization through the FDA, Chamberland said.  Phase three would start at the end of 2021.

Tetra Bio-Pharma says it has already contracted with Dalton Pharma Services to manufacture the active pharmaceutical ingredient (API), HU-308, and the finished drug product ARDS-003.
 

This article first appeared on Medscape.com.