Ob.Gyn. News

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.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial disclosures.

Pregnancy and the postpartum period are a “very vulnerable time for mental disorders,” according to Henry A. Nasrallah, MD.

Courtney Hale/Getty Images

“Those changes that are helping pregnancy can also have psychiatric and psychopathological implications,” Dr. Nasrallah said in a virtual meeting presented by Current Psychiatry and the American Academy of Clinical Psychiatrists.

Numerous dramatic changes in physiology, immune functions, cognition, neuroplasticity, and behavior occur during pregnancy, noted Dr. Nasrallah of the University of Cincinnati. For example, the volume of the brain actually decreases during pregnancy, but brain size recovers over the 6 months after delivery. “Clearly, this is a transitional and a transient phenomenon,” he said. “The decrease in brain volume is associated with changes in brain metabolism and an increase in intracellular pH after delivery.”

But these changes can also carry risks for psychiatric disorders, Dr. Nasrallah explained. Changes in the hippocampus, which is “very plastic throughout adulthood,” have been linked to aging, cognition, pregnancy, and motherhood. “The hippocampus is the ‘Grand Central Station’ of memory in the brain, and the hippocampus is affected by neurodegenerative and psychiatric disorders, which disproportionately affect women,” he said at the meeting, presented by Global Academy for Medical Education.

Dr. Nasrallah said the hippocampus has particular susceptibility during pregnancy and in the postpartum period, or in women who have previously been pregnant.

Gender of the fetus can even affect the health of the mother, he added. In women who are pregnant with male fetuses, working memory and spatial ability are higher than in women who are pregnant with female fetuses, Dr. Nasrallah said. This is tied to higher numbers of proinflammatory cytokines present in male fetuses. In female fetuses, there are lower levels of interferon-gamma and interleukin (IL)-12 in the first trimester, and higher levels of IL-1 beta, tumor necrosis factor B, IL-5, and IL-10 in the second trimester.

In particular, the perinatal period is a time of great risk for depression and anxiety. Women are also at risk for postpartum depression, particularly women with bipolar disorder, Dr. Nasrallah said.

“Cytokine interleukin-10 and interleukin-6 are both increased during psychosis and during depression, so you can see the vulnerability for developing postpartum depression.” Some women “have other genes that make them susceptible for mood disorders, and the pregnancy can push them over the edge,” he said.

If women have bipolar disorder prior to delivery, “they have a very high risk of postpartum depression, possibly because of this immune dysregulation that serves the pregnancy, but unfortunately makes the woman vulnerable for postpartum psychiatric disorders,” Dr. Nasrallah said.

The effects of having children extend into middle age, Dr. Nasrallah said. Research has shown giving birth to more than one to two children can affect a woman’s risk for Alzheimer’s disease and risk for early-onset of the disease. Women who have three or fewer children later in life are also more likely to live longer, he said. In general, a longer reproductive period, duration of breastfeeding, and low number of pregnancies result in better cognition, while younger age at first pregnancy leads to worse cognition.

So-called pregnancy brain causes some cognitive functions to decline, and women may experience trouble concentrating and memory disturbance. “Other functions increase for the sake of the baby,” including a high reaction to threatening stimuli, absent-mindedness, motivation, reward, fear, executive functions, social cognition, salience, and attachment, Dr. Nasrallah said. In some cases, hormone-driven remodeling of the maternal brain can cause postpartum psychosis, which can reduce the anterior cingulate cortex, left parahippocampal gyrus volume, and left superior temporal gyrus volume.

Most changes in the brain, however, appear to be temporary, Dr. Nasrallah noted. Executive function improves 2-6 months after delivery, which includes goal and directed behavior, working memory, inhibitory function, and cognitive flexibility. In the postpartum period, “the gray matter increases in the first 3-4 months, especially in the brain areas that are involved in maternal behavior that includes amygdala, hypothalamus, and prefrontal cortex,” he added. “All of those changes correlate with positive maternal attachment, and so that makes it easier for the mother to bond with the baby.

“Don’t think of it as a negative,” he said. “The decline in brain volume is actually associated with better mothering and increased attachment between the mother and the baby, which is vital for survival of the baby.”

Global Academy and this news organization are owned by the same parent company. Dr. Nasrallah reports no relevant financial 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.

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.

Long-term outcomes now being reported confirm earlier reports from the same trial showing efficacy for the use of targeted intraoperative radiotherapy (TARGIT) in patients with early breast cancer.

This novel approach, which delivers a one-off blast of radiation directed at the tumor bed and is given during lumpectomy, has similar efficacy and lowers non–breast cancer mortality when compared with whole-breast external beam radiotherapy (EBRT), which is delivered in fractions over 3-6 weeks after surgery.

Giving the boost of radiation during surgery has numerous benefits, say the authors: it is more convenient for patients and saves on healthcare costs.

However, the controversy over local recurrence rates, sparked by the earlier results, still remains. The difference in the 5-year local recurrence rate between TARGIT and EBRT was within the 2.5% margin for non-inferiority: the rate was 2.11% in 1140 TARGIT recipients, compared with 0.95% in 1158 EBRT recipients, for a difference of 1.16% (13 recurrences).

The new longer-term results from the TARGIT-A trial were published August 20 in the BMJ, and confirm earlier results from this trial published in 2014. Meanwhile, other approaches to intraoperative radiotherapy (IORT) have also been reported.  

Nevertheless, whole-breast radiotherapy remains the standard of care today, note the authors.

“The biggest battle the TARGIT investigator family has faced is our challenge to the conventional dogma that radiotherapy has to be given in multiple daily doses, and moreover that whole-breast radiotherapy is always essential,” said lead author Jayant Vaidya, MD, professor of surgery and oncology at University College London, UK. He was one of the team of investigators that together developed the TARGIT approach in the 1990s, as he recalls in a related BMJ blog post.

It is unclear whether the TARGIT-A long-term outcomes will change practice, Rachel Jimenez, MD, associate program director of the Harvard Radiation Oncology Residency Program and assistant professor of radiation oncology at Massachusetts General Hospital, Boston, told Medscape Medical News.

She noted there was controversy and debate over the earlier reports from TARGIT-A, and those findings “did little to change practice patterns over the past 6 years,” she said.

“With the publication of longer-term follow-up, my expectation would be that perceptions of IORT will remain unchanged in the radiation oncology community, and that those previously supportive of the TARGIT-A approach will continue to embrace it while those initially skeptical will be unlikely to change practice despite the longer-term results,” she said.

“However, despite the controversy surrounding TARGIT-A, it is heartening as a clinician who cares for breast cancer patients to see a trend within the early breast cancer clinical trials space toward the evaluation of increasingly targeted and abbreviated courses of radiation,” Jimenez commented.
 

Details of new long-term results

TARGIT-A is an open-label, 32-center multinational study conducted in 2298 women aged 45 years or older with early-stage invasive ductal carcinoma who were eligible for breast-conserving surgery. Between March 24, 2000, and June 25, 2012, participants were randomized 1:1 to risk-adapted TARGIT immediately after lumpectomy or to whole-breast EBRT delivered for the standard 3-6 week daily fractionated course.

At a median follow-up of 8.6 years — with some patients followed for nearly 19 years — no significant difference was seen between the treatment groups in local recurrence-free survival (167 vs 147 events; hazard ratio, 1.13); invasive local recurrence-free survival (154 vs 146 events; HR, 1.04); mastectomy-free survival (170 vs 175 events; HR, 0.96); distant disease-free survival (133 vs 148 events; HR, 0.88); overall survival (110 vs 131 events; HR, 0.82); or breast cancer mortality (6 vs 57 events; HR, 1.12).

“Mortality from other causes was significantly lower (45 vs 74 events; HR, 0.59),” the authors note.
 

Controversy of Earlier Results

Vaidya and colleagues comment that these new results confirm earlier findings from this trial. They were initially presented in 2012 by Vaidya at the San Antonio Breast Cancer Symposium and subsequently published in The Lancet, as previously reported by Medscape Medical News. Those earlier results showed a trend toward lower overall mortality with TARGIT (absolute difference, -1.3%; P = .01) and significantly fewer deaths from causes other than breast cancer (absolute difference, -2.1%; P = .009).

However, TARGIT was associated with slightly more same-breast recurrences at that time (3.3% vs 1.3%; P = 0.42), even though this was still within the 2.5% margin for non-inferiority.

The new longer-term results show a similar pattern.

It was this risk of same-breast recurrences that sparked the heated debate over the findings, as some breast cancer experts argued that this needs to be weighed against various potential benefits of IORT for patients: greater convenience, potentially improved mortality, and lower costs.

The extent of that “vigorous debate” was highlighted in 2015 in the International Journal of Radiation Oncology, Biology, Physics, (the Red Journal), in which editor-in-chief Anthony Zietman, MD, shared numerous letters to the editor, written in response to two editorials, that contained “passionately and articulately expressed” views from “senior investigators and breast cancer physicians from around the globe.”

At the same time, in 2015, another approach to IORT was reported at the American Society for Radiation Oncology (ASTRO) annual meeting and simultaneously published online in The Lancet. This was accelerated partial-breast irradiation (APBI) delivered directly to the tumor bed using multicatheter brachytherapy at the time of lumpectomy in women with early breast cancer. The results showed outcomes that were comparable with whole-breast irradiation, but with fewer side effects.

Those findings prompted a 2016 update to the ASTRO consensus statement on APBI to note that APBI after lumpectomy may be suitable for more women with early-stage breast cancer, including younger patients and those with ductal carcinoma in situ.

In comments to Medscape Medical News, Jimenez noted that several recent studies have shown efficacy for various IORT approaches. There have been two phase 3 non-inferiority studies, namely the NSABP B-39 and the RAPID trial, that evaluate the use of APBI in lieu of whole-breast radiation. There have also been two trials as well as the evaluation of a 5-day ultrahypofractionated whole-breast radiation course per the UK Fast and Fast-Forward trials, compared with several weeks of whole-breast radiation.  

“Collectively, these studies lend support for fewer and/or more targeted radiotherapy treatments for our patients and have the potential to reduce patient burden and limit healthcare costs,” Jimenez told Medscape Medical News.

Indeed, the TARGIT-A researchers write that their long-term findings “have shown that risk-adapted single-dose TARGIT-IORT given during lumpectomy can effectively replace the mandatory use of several weeks of daily postoperative whole-breast radiotherapy in patients with breast cancer undergoing breast conservation.”

Given the numerous benefits to patients that this approach provides, the choice should ultimately rest with the patient, the authors conclude.

An extended follow-up of the trial (TARGIT-Ex) is ongoing, as is the TARGIT-B(oost) trial looking at TARGIT-IORT as a tumor bed boost with EBRT boost in younger women and those with higher-risk disease.

The TARGIT-A trial was sponsored by University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre and funded by UCLH Charities, the National Institute for Health Research Health Technology Assessment program, Ninewells Cancer Campaign, the National Health and Medical Research Council, and the German Federal Ministry of Education and Research. The authors reported numerous disclosures, as detailed in the publication.
 

This article first appeared on Medscape.com.

Long-term outcomes now being reported confirm earlier reports from the same trial showing efficacy for the use of targeted intraoperative radiotherapy (TARGIT) in patients with early breast cancer.

This novel approach, which delivers a one-off blast of radiation directed at the tumor bed and is given during lumpectomy, has similar efficacy and lowers non–breast cancer mortality when compared with whole-breast external beam radiotherapy (EBRT), which is delivered in fractions over 3-6 weeks after surgery.

Giving the boost of radiation during surgery has numerous benefits, say the authors: it is more convenient for patients and saves on healthcare costs.

However, the controversy over local recurrence rates, sparked by the earlier results, still remains. The difference in the 5-year local recurrence rate between TARGIT and EBRT was within the 2.5% margin for non-inferiority: the rate was 2.11% in 1140 TARGIT recipients, compared with 0.95% in 1158 EBRT recipients, for a difference of 1.16% (13 recurrences).

The new longer-term results from the TARGIT-A trial were published August 20 in the BMJ, and confirm earlier results from this trial published in 2014. Meanwhile, other approaches to intraoperative radiotherapy (IORT) have also been reported.  

Nevertheless, whole-breast radiotherapy remains the standard of care today, note the authors.

“The biggest battle the TARGIT investigator family has faced is our challenge to the conventional dogma that radiotherapy has to be given in multiple daily doses, and moreover that whole-breast radiotherapy is always essential,” said lead author Jayant Vaidya, MD, professor of surgery and oncology at University College London, UK. He was one of the team of investigators that together developed the TARGIT approach in the 1990s, as he recalls in a related BMJ blog post.

It is unclear whether the TARGIT-A long-term outcomes will change practice, Rachel Jimenez, MD, associate program director of the Harvard Radiation Oncology Residency Program and assistant professor of radiation oncology at Massachusetts General Hospital, Boston, told Medscape Medical News.

She noted there was controversy and debate over the earlier reports from TARGIT-A, and those findings “did little to change practice patterns over the past 6 years,” she said.

“With the publication of longer-term follow-up, my expectation would be that perceptions of IORT will remain unchanged in the radiation oncology community, and that those previously supportive of the TARGIT-A approach will continue to embrace it while those initially skeptical will be unlikely to change practice despite the longer-term results,” she said.

“However, despite the controversy surrounding TARGIT-A, it is heartening as a clinician who cares for breast cancer patients to see a trend within the early breast cancer clinical trials space toward the evaluation of increasingly targeted and abbreviated courses of radiation,” Jimenez commented.
 

Details of new long-term results

TARGIT-A is an open-label, 32-center multinational study conducted in 2298 women aged 45 years or older with early-stage invasive ductal carcinoma who were eligible for breast-conserving surgery. Between March 24, 2000, and June 25, 2012, participants were randomized 1:1 to risk-adapted TARGIT immediately after lumpectomy or to whole-breast EBRT delivered for the standard 3-6 week daily fractionated course.

At a median follow-up of 8.6 years — with some patients followed for nearly 19 years — no significant difference was seen between the treatment groups in local recurrence-free survival (167 vs 147 events; hazard ratio, 1.13); invasive local recurrence-free survival (154 vs 146 events; HR, 1.04); mastectomy-free survival (170 vs 175 events; HR, 0.96); distant disease-free survival (133 vs 148 events; HR, 0.88); overall survival (110 vs 131 events; HR, 0.82); or breast cancer mortality (6 vs 57 events; HR, 1.12).

“Mortality from other causes was significantly lower (45 vs 74 events; HR, 0.59),” the authors note.
 

Controversy of Earlier Results

Vaidya and colleagues comment that these new results confirm earlier findings from this trial. They were initially presented in 2012 by Vaidya at the San Antonio Breast Cancer Symposium and subsequently published in The Lancet, as previously reported by Medscape Medical News. Those earlier results showed a trend toward lower overall mortality with TARGIT (absolute difference, -1.3%; P = .01) and significantly fewer deaths from causes other than breast cancer (absolute difference, -2.1%; P = .009).

However, TARGIT was associated with slightly more same-breast recurrences at that time (3.3% vs 1.3%; P = 0.42), even though this was still within the 2.5% margin for non-inferiority.

The new longer-term results show a similar pattern.

It was this risk of same-breast recurrences that sparked the heated debate over the findings, as some breast cancer experts argued that this needs to be weighed against various potential benefits of IORT for patients: greater convenience, potentially improved mortality, and lower costs.

The extent of that “vigorous debate” was highlighted in 2015 in the International Journal of Radiation Oncology, Biology, Physics, (the Red Journal), in which editor-in-chief Anthony Zietman, MD, shared numerous letters to the editor, written in response to two editorials, that contained “passionately and articulately expressed” views from “senior investigators and breast cancer physicians from around the globe.”

At the same time, in 2015, another approach to IORT was reported at the American Society for Radiation Oncology (ASTRO) annual meeting and simultaneously published online in The Lancet. This was accelerated partial-breast irradiation (APBI) delivered directly to the tumor bed using multicatheter brachytherapy at the time of lumpectomy in women with early breast cancer. The results showed outcomes that were comparable with whole-breast irradiation, but with fewer side effects.

Those findings prompted a 2016 update to the ASTRO consensus statement on APBI to note that APBI after lumpectomy may be suitable for more women with early-stage breast cancer, including younger patients and those with ductal carcinoma in situ.

In comments to Medscape Medical News, Jimenez noted that several recent studies have shown efficacy for various IORT approaches. There have been two phase 3 non-inferiority studies, namely the NSABP B-39 and the RAPID trial, that evaluate the use of APBI in lieu of whole-breast radiation. There have also been two trials as well as the evaluation of a 5-day ultrahypofractionated whole-breast radiation course per the UK Fast and Fast-Forward trials, compared with several weeks of whole-breast radiation.  

“Collectively, these studies lend support for fewer and/or more targeted radiotherapy treatments for our patients and have the potential to reduce patient burden and limit healthcare costs,” Jimenez told Medscape Medical News.

Indeed, the TARGIT-A researchers write that their long-term findings “have shown that risk-adapted single-dose TARGIT-IORT given during lumpectomy can effectively replace the mandatory use of several weeks of daily postoperative whole-breast radiotherapy in patients with breast cancer undergoing breast conservation.”

Given the numerous benefits to patients that this approach provides, the choice should ultimately rest with the patient, the authors conclude.

An extended follow-up of the trial (TARGIT-Ex) is ongoing, as is the TARGIT-B(oost) trial looking at TARGIT-IORT as a tumor bed boost with EBRT boost in younger women and those with higher-risk disease.

The TARGIT-A trial was sponsored by University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre and funded by UCLH Charities, the National Institute for Health Research Health Technology Assessment program, Ninewells Cancer Campaign, the National Health and Medical Research Council, and the German Federal Ministry of Education and Research. The authors reported numerous disclosures, as detailed in the publication.
 

This article first appeared on Medscape.com.

Long-term outcomes now being reported confirm earlier reports from the same trial showing efficacy for the use of targeted intraoperative radiotherapy (TARGIT) in patients with early breast cancer.

This novel approach, which delivers a one-off blast of radiation directed at the tumor bed and is given during lumpectomy, has similar efficacy and lowers non–breast cancer mortality when compared with whole-breast external beam radiotherapy (EBRT), which is delivered in fractions over 3-6 weeks after surgery.

Giving the boost of radiation during surgery has numerous benefits, say the authors: it is more convenient for patients and saves on healthcare costs.

However, the controversy over local recurrence rates, sparked by the earlier results, still remains. The difference in the 5-year local recurrence rate between TARGIT and EBRT was within the 2.5% margin for non-inferiority: the rate was 2.11% in 1140 TARGIT recipients, compared with 0.95% in 1158 EBRT recipients, for a difference of 1.16% (13 recurrences).

The new longer-term results from the TARGIT-A trial were published August 20 in the BMJ, and confirm earlier results from this trial published in 2014. Meanwhile, other approaches to intraoperative radiotherapy (IORT) have also been reported.  

Nevertheless, whole-breast radiotherapy remains the standard of care today, note the authors.

“The biggest battle the TARGIT investigator family has faced is our challenge to the conventional dogma that radiotherapy has to be given in multiple daily doses, and moreover that whole-breast radiotherapy is always essential,” said lead author Jayant Vaidya, MD, professor of surgery and oncology at University College London, UK. He was one of the team of investigators that together developed the TARGIT approach in the 1990s, as he recalls in a related BMJ blog post.

It is unclear whether the TARGIT-A long-term outcomes will change practice, Rachel Jimenez, MD, associate program director of the Harvard Radiation Oncology Residency Program and assistant professor of radiation oncology at Massachusetts General Hospital, Boston, told Medscape Medical News.

She noted there was controversy and debate over the earlier reports from TARGIT-A, and those findings “did little to change practice patterns over the past 6 years,” she said.

“With the publication of longer-term follow-up, my expectation would be that perceptions of IORT will remain unchanged in the radiation oncology community, and that those previously supportive of the TARGIT-A approach will continue to embrace it while those initially skeptical will be unlikely to change practice despite the longer-term results,” she said.

“However, despite the controversy surrounding TARGIT-A, it is heartening as a clinician who cares for breast cancer patients to see a trend within the early breast cancer clinical trials space toward the evaluation of increasingly targeted and abbreviated courses of radiation,” Jimenez commented.
 

Details of new long-term results

TARGIT-A is an open-label, 32-center multinational study conducted in 2298 women aged 45 years or older with early-stage invasive ductal carcinoma who were eligible for breast-conserving surgery. Between March 24, 2000, and June 25, 2012, participants were randomized 1:1 to risk-adapted TARGIT immediately after lumpectomy or to whole-breast EBRT delivered for the standard 3-6 week daily fractionated course.

At a median follow-up of 8.6 years — with some patients followed for nearly 19 years — no significant difference was seen between the treatment groups in local recurrence-free survival (167 vs 147 events; hazard ratio, 1.13); invasive local recurrence-free survival (154 vs 146 events; HR, 1.04); mastectomy-free survival (170 vs 175 events; HR, 0.96); distant disease-free survival (133 vs 148 events; HR, 0.88); overall survival (110 vs 131 events; HR, 0.82); or breast cancer mortality (6 vs 57 events; HR, 1.12).

“Mortality from other causes was significantly lower (45 vs 74 events; HR, 0.59),” the authors note.
 

Controversy of Earlier Results

Vaidya and colleagues comment that these new results confirm earlier findings from this trial. They were initially presented in 2012 by Vaidya at the San Antonio Breast Cancer Symposium and subsequently published in The Lancet, as previously reported by Medscape Medical News. Those earlier results showed a trend toward lower overall mortality with TARGIT (absolute difference, -1.3%; P = .01) and significantly fewer deaths from causes other than breast cancer (absolute difference, -2.1%; P = .009).

However, TARGIT was associated with slightly more same-breast recurrences at that time (3.3% vs 1.3%; P = 0.42), even though this was still within the 2.5% margin for non-inferiority.

The new longer-term results show a similar pattern.

It was this risk of same-breast recurrences that sparked the heated debate over the findings, as some breast cancer experts argued that this needs to be weighed against various potential benefits of IORT for patients: greater convenience, potentially improved mortality, and lower costs.

The extent of that “vigorous debate” was highlighted in 2015 in the International Journal of Radiation Oncology, Biology, Physics, (the Red Journal), in which editor-in-chief Anthony Zietman, MD, shared numerous letters to the editor, written in response to two editorials, that contained “passionately and articulately expressed” views from “senior investigators and breast cancer physicians from around the globe.”

At the same time, in 2015, another approach to IORT was reported at the American Society for Radiation Oncology (ASTRO) annual meeting and simultaneously published online in The Lancet. This was accelerated partial-breast irradiation (APBI) delivered directly to the tumor bed using multicatheter brachytherapy at the time of lumpectomy in women with early breast cancer. The results showed outcomes that were comparable with whole-breast irradiation, but with fewer side effects.

Those findings prompted a 2016 update to the ASTRO consensus statement on APBI to note that APBI after lumpectomy may be suitable for more women with early-stage breast cancer, including younger patients and those with ductal carcinoma in situ.

In comments to Medscape Medical News, Jimenez noted that several recent studies have shown efficacy for various IORT approaches. There have been two phase 3 non-inferiority studies, namely the NSABP B-39 and the RAPID trial, that evaluate the use of APBI in lieu of whole-breast radiation. There have also been two trials as well as the evaluation of a 5-day ultrahypofractionated whole-breast radiation course per the UK Fast and Fast-Forward trials, compared with several weeks of whole-breast radiation.  

“Collectively, these studies lend support for fewer and/or more targeted radiotherapy treatments for our patients and have the potential to reduce patient burden and limit healthcare costs,” Jimenez told Medscape Medical News.

Indeed, the TARGIT-A researchers write that their long-term findings “have shown that risk-adapted single-dose TARGIT-IORT given during lumpectomy can effectively replace the mandatory use of several weeks of daily postoperative whole-breast radiotherapy in patients with breast cancer undergoing breast conservation.”

Given the numerous benefits to patients that this approach provides, the choice should ultimately rest with the patient, the authors conclude.

An extended follow-up of the trial (TARGIT-Ex) is ongoing, as is the TARGIT-B(oost) trial looking at TARGIT-IORT as a tumor bed boost with EBRT boost in younger women and those with higher-risk disease.

The TARGIT-A trial was sponsored by University College London Hospitals (UCLH) Comprehensive Biomedical Research Centre and funded by UCLH Charities, the National Institute for Health Research Health Technology Assessment program, Ninewells Cancer Campaign, the National Health and Medical Research Council, and the German Federal Ministry of Education and Research. The authors reported numerous disclosures, as detailed in the publication.
 

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.

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.

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

Researchers in Hong Kong say they’ve confirmed that a person can be infected with COVID-19 twice.

There have been sporadic accounts on social media sites of people who say they’ve gotten COVID-19 twice. But scientists have been skeptical about that possibility, saying there’s no evidence it happens.

The new proof comes from a 33-year-old man in Hong Kong who first caught COVID-19 in March. He was tested for the coronavirus after he developed a cough, sore throat, fever, and a headache for 3 days. He stayed in the hospital until he twice tested negative for the virus in mid-April.

On Aug. 15, the man returned to Hong Kong from a recent trip to Spain and the United Kingdom, areas that have recently seen a resurgence of COVID-19 cases. At the airport, he was screened for COVID-19 with a test that checks saliva for the virus. He tested positive, but this time, had no symptoms. He was taken to the hospital for monitoring. His viral load – the amount of virus he had in his body – went down over time, suggesting that his immune system was taking care of the intrusion on its own.

The special thing about his case is that each time he was hospitalized, doctors sequenced the genome of the virus that infected him. It was slightly different from one infection to the next, suggesting that the virus had mutated – or changed – in the 4 months between his infections. It also proves that it’s possible for this coronavirus to infect the same person twice.

Experts with the World Health Organization responded to the case at a news briefing.

“What we are learning about infection is that people do develop an immune response. What is not completely clear yet is how strong that immune response is and for how long that immune response lasts,” said Maria Van Kerkhove, PhD, an infectious disease epidemiologist with the World Health Organization in Geneva, Switzerland.

A study on the man’s case is being prepared for publication in the journal Clinical Infectious Diseases. Experts say the finding shouldn’t cause alarm, but it does have important implications for the development of herd immunity and efforts to come up with vaccines and treatments.

“This appears to be pretty clear-cut evidence of reinfection because of sequencing and isolation of two different viruses,” said Gregory Poland, MD, an expert on vaccine development and immunology at the Mayo Clinic in Rochester, Minn. “The big unknown is how often is this happening,” he said. More studies are needed to learn whether this was a rare case or something that is happening often.
 

Past experience guides present

Until we know more, Dr. Poland said, the possibility of getting COVID-19 twice shouldn’t make anyone worry.

This also happens with other kinds of coronaviruses – the ones that cause common colds. Those coronaviruses change slightly each year as they circle the globe, which allows them to keep spreading and causing their more run-of-the-mill kind of misery.

It also happens with seasonal flu. It is the reason people have to get vaccinated against the flu year after year, and why the flu vaccine has to change slightly each year in an effort to keep up with the ever-evolving influenza virus.

“We’ve been making flu vaccines for 80 years, and there are clinical trials happening as we speak to find new and better influenza vaccines,” Dr. Poland said.

There has been other evidence the virus that causes COVID-19 can change this way, too. Researchers at Howard Hughes Medical Center, at Rockefeller University in New York, recently used a key piece of the SARS-CoV-2 virus – the genetic instructions for its spike protein – to repeatedly infect human cells. Scientists watched as each new generation of the virus went on to infect a new batch of cells. Over time, as it copied itself, some of the copies changed their genes to allow them to survive after scientists attacked them with neutralizing antibodies. Those antibodies are among the main weapons used by the immune system to recognize and disable a virus.

Though that study is still a preprint, which means it hasn’t yet been reviewed by outside experts, the authors wrote that their findings suggest the virus can change in ways that help it evade our immune system. If true, they wrote in mid-July, it means reinfection is possible, especially in people who have a weak immune response to the virus the first time they encounter it.
 

Good news

That seems to be true in the case of the man from Hong Kong. When doctors tested his blood to look for antibodies to the virus, they didn’t find any. That could mean that he either had a weak immune response to the virus the first time around, or that the antibodies he made during his first infection diminished over time. But during his second infection, he quickly developed more antibodies, suggesting that the second infection acted a little bit like a booster to fire up his immune system. That’s probably the reason he didn’t have any symptoms the second time, too.

That’s good news, Dr. Poland said. It means our bodies can get better at fighting off the COVID-19 virus and that catching it once means the second time might not be so bad.

But the fact that the virus can change quickly this way does have some impact on the effort to come up with a vaccine that works well.

“I think a potential implication of this is that we will have to give booster doses. The question is how frequently,” Dr. Poland said. That will depend on how fast the virus is changing, and how often reinfection is happening in the real world.

“I’m a little surprised at 4½ months,” Dr. Poland said, referencing the time between the Hong Kong man’s infections. “I’m not surprised by, you know, I got infected last winter and I got infected again this winter,” he said.

It also suggests that immune-based therapies such as convalescent plasma and monoclonal antibodies may be of limited help over time, since the virus might be changing in ways that help it outsmart those treatments.

Convalescent plasma is essentially a concentrated dose of antibodies from people who have recovered from a COVID-19 infection. As the virus changes, the antibodies in that plasma may not work as well for future infections.

Drug companies have learned to harness the power of monoclonal antibodies as powerful treatments against cancer and other diseases. Monoclonal antibodies, which are mass-produced in a lab, mimic the body’s natural defenses against a pathogen. Just like the virus can become resistant to natural immunity, it can change in ways that help it outsmart lab-created treatments. Some drug companies that are developing monoclonal antibodies to fight COVID-19 have already prepared for that possibility by making antibody cocktails that are designed to disable the virus by locking onto it in different places, which may help prevent it from developing resistance to those therapies.

“We have a lot to learn,” Dr. Poland said. “Now that the proof of principle has been established, and I would say it has with this man, and with our knowledge of seasonal coronaviruses, we need to look more aggressively to define how often this occurs.”

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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

The persistence of long-term symptoms in some individuals with COVID-19 illness has opened up a new line of research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and other chronic postviral illnesses.

Some patients who had COVID-19 continue to have symptoms weeks to months later, even after they no longer test positive for the virus. In two recent reports – one published in JAMA in July and another published in Morbidity and Mortality Weekly Report in August – chronic fatigue was listed as the top symptom among individuals still feeling unwell beyond 2 weeks after COVID-19 onset.

Although some of the reported persistent symptoms appear specific to SARS-CoV-2 – such as cough, chest pain, and dyspnea – others overlap with the diagnostic criteria for ME/CFS, which is defined by substantial, profound fatigue for at least 6 months, postexertional malaise, unrefreshing sleep, and one or both of orthostatic intolerance and/or cognitive impairment. Although the etiology of ME/CFS is unclear, the condition commonly arises following a viral illness.

At the virtual meeting of the International Association for Chronic Fatigue Syndrome/Myalgic Encephalomyelitis August 21, the opening session was devoted to research documenting the extent to which COVID-19 survivors subsequently meet ME/CFS criteria, and to exploring underlying mechanisms.

“It offers a lot of opportunities for us to study potentially early ME/CFS and how it develops, but in addition, a lot of the research that has been done on ME/CFS may also provide answers for COVID-19,” IACFS/ME vice president Lily Chu, MD, said in an interview.
 

A hint from the SARS outbreak

This isn’t the first time researchers have seen a possible link between a coronavirus and ME/CFS, Harvey Moldofsky, MD, told attendees. To illustrate that point, Dr. Moldofsky, of the department of psychiatry (emeritus) at the University of Toronto, reviewed data from a previously published case-controlled study, which included 22 health care workers who had been infected in 2003 with SARS-CoV-1 and continued to report chronic fatigue, musculoskeletal pain, and disturbed and unrefreshing sleep with EEG-documented sleep disturbances 1-3 years following the illness. None had been able to return to work by 1 year.

“We’re looking at similar symptoms now” among survivors of COVID-19, Dr. Moldofsky said. “[T]he key issue is that we have no idea of its prevalence. … We need epidemiologic studies.”
 

Distinguishing ME/CFS from other post–COVID-19 symptoms

Not everyone who has persistent symptoms after COVID-19 will develop ME/CFS, and distinguishing between cases may be important.

Clinically, Dr. Chu said, one way to assess whether a patient with persistent COVID-19 symptoms might be progressing to ME/CFS is to ask him or her specifically about the level of fatigue following physical exertion and the timing of any fatigue. With ME/CFS, postexertional malaise often involves a dramatic exacerbation of symptoms such as fatigue, pain, and cognitive impairment a day or 2 after exertion rather than immediately following it. In contrast, shortness of breath during exertion isn’t typical of ME/CFS.

Objective measures of ME/CFS include low natural killer cell function (the test can be ordered from commercial labs but requires rapid transport of the blood sample), and autonomic dysfunction assessed by a tilt-table test.

While there is currently no cure for ME/CFS, diagnosing it allows for the patient to be taught “pacing” in which the person conserves his or her energy by balancing activity with rest. “That type of behavioral technique is valuable for everyone who suffers from a chronic disease with fatigue. It can help them be more functional,” Dr. Chu said.

If a patient appears to be exhibiting signs of ME/CFS, “don’t wait until they hit the 6-month mark to start helping them manage their symptoms,” she said. “Teaching pacing to COVID-19 patients who have a lot of fatigue isn’t going to harm them. As they get better they’re going to just naturally do more. But if they do have ME/CFS, [pacing] stresses their system less, since the data seem to be pointing to deficiencies in producing energy.”
 

Will COVID-19 unleash a new wave of ME/CFS patients?

Much of the session at the virtual meeting was devoted to ongoing studies. For example, Leonard Jason, PhD, of the Center for Community Research at DePaul University, Chicago, described a prospective study launched in 2014 that looked at risk factors for developing ME/CFS in college students who contracted infectious mononucleosis as a result of Epstein-Barr virus. Now, his team is also following students from the same cohort who develop COVID-19.

Because the study included collection of baseline biological samples, the results could help reveal predisposing factors associated with long-term illness from either virus.

Another project, funded by the Open Medicine Foundation, will follow patients who are discharged from the ICU following severe COVID-19 illness. Blood, urine, and cerebrospinal fluid will be collected from those with persistent symptoms at 6 months, along with questionnaire data. At 18-24 months, those who continue to report symptoms will undergo more intensive evaluation using genomics, metabolomics, and proteomics.

“We’re taking advantage of this horrible situation, hoping to understand how a serious viral infection might lead to ME/CFS,” said lead investigator Ronald Tompkins, MD, ScD, chief medical officer at the Open Medicine Foundation and a faculty member at Harvard Medical School, Boston. The results, he said, “might give us insight into potential drug targets or biomarkers useful for prevention and treatment strategies.”

Meanwhile, Sadie Whittaker, PhD, head of the Solve ME/CFS initiative, described her organization’s new plan to use their registry to prospectively track the impact of COVID-19 on people with ME/CFS. 

She noted that they’ve also teamed up with “long-COVID” communities including Body Politic. “Our goal is to form a coalition to study together or at least harmonize data … and understand what’s going on through the power of bigger sample sizes,” Dr. Whittaker said.

None of the speakers disclosed relevant financial relationships.

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