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GLP-1s Treat and Even Reverse Some Forms of Liver Disease
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
In the past two decades, the global prevalence of metabolic dysfunction–associated steatohepatitis (MASH) has increased dramatically as a result of the obesity epidemic. Researchers project that by 2040, rates of MASH will increase by 55%. Prior to that most liver diseases were caused by alcohol use and hepatitis C, a viral infection that primarily affects the liver.
MASH, a preventable form of liver disease previously called nonalcoholic fatty liver disease, is caused by a buildup of visceral fat cells that accumulate on top of the internal organs, in this case the liver, and keep it from functioning properly. The liver’s primary role is to filter blood, nutrients, and bile used for digestion, as well as to remove toxins from the body. Excess fat cells blanket the liver and keep it from working at full capacity.
Fat cells are also metabolically active and can cause a chronic state of inflammation in the part of the body where they reside. Over time, these fat cells can cause cirrhosis of the liver, or permanent scarring. Once patients reach this stage, the only option is a liver transplant.
New Research on GLP-1 Agonists and MASH
Until recently, the lone treatment for early-stage MASH was weight loss to reduce the number of fat cells that surround the internal organs. But new research has shown that glucagon-like peptide 1 (GLP-1) agonists can reduce and even reverse the condition. In a study published in April, researchers were able to show that semaglutide resolved fatty liver and inflammation in over 60% of cases and decreased scar tissue in just over a third of patients.
“These findings suggest that semaglutide may prevent fatty liver disease from progressing to cirrhosis and can indeed reverse the course of the disease,” said Arun J. Sanyal, MD, study author and director of the Stravitz-Sanyal Institute for Liver Disease and Metabolic Health at Virginia Commonwealth University in Richmond, Virginia.
Another study published last year had a similar finding, showing that GLP-1 agonists were associated with less progression of the disease and reduced mortality in patients with MASH and diabetes. Another large-scale observational study found that GLP-1s reduced the risk for hepatic failure, which occurs when the liver is unable to perform basic functions, as well as liver cancer, both of which are downstream consequences of MASH.
How GLP-1s Improve Liver Function
“These medications reduce fat burden, which results in fat loss everywhere, including around the liver,” said Ziyad Al-Aly, MD, an assistant professor in the Division of General Medicine & Geriatrics at Washington University School of Medicine in St. Louis. “When fat cells are reduced in size and volume, the normal liver cells have more room to grow and function.”
These medications also seem to work on reducing the inflammation and oxidative stress caused by metabolic disease, which allows for a better environment for the liver to function.
“Fat is not an inert tissue, it’s metabolically active, causing a slow burn to all the cells surrounding it,” said Al-Aly. These medications keep the disease from progressing and reduce scarring, which improves the damage that’s already been done, he said.
Changing How Liver Disease Is Diagnosed
Physicians need to be vigilant in the way that they screen for the condition, said Charu Sawhney, DO, MPH, of Harbor Health in Round Rock, Texas. She said that if liver enzymes appear even slightly elevated, there still could be a reason to utilize GLP-1s to prevent later-stage MASH.
“Normal levels for liver enzymes in some patients can be lower than what labs show,” said Sawhney. This is especially true if a patient has other metabolic risk factors such as diabetes, obesity, or high cholesterol.
If liver enzymes continue to go up even after diet and lifestyle changes, patients might require liver imaging, specifically a wave-based ultrasound called elastography, which measures the elasticity or stiffness of tissues on the liver and can judge if certain portions of it have scarred or hardened. When liver cells change texture and become harder, the scan can estimate levels of fibrosis and, therefore, the stage of MASH that a patient is in.
Additionally, the severity of fatty liver disease depends on other factors besides weight and can sometimes be surprising.
“How bad fatty liver disease is in a patient isn’t always related to how much weight someone has gained,” said Carolynn Francavilla, MD, a nationally recognized obesity physician who owns and operates Green Mountain Partners for Health and Colorado Weight Care, both in Denver.
It’s important for physicians to realize that some patients with fatty liver disease might not have obesity as would be expected. For these patients, adipose tissue seems to accumulate on the liver before it does on other parts of the body. This could be related to the quality of our food system, including the use of sugar substitutes like high fructose corn syrup, which research has shown is even harder on the liver. There might also be a genetic propensity toward fat storage around the organs.
A New Way to Treat MASH
, said Francavilla. Right now, there’s not an official approval from the US Food and Drug Administration (FDA) for prescribing GLP-1s in patients with MASH, but Francavilla hopes that it’s forthcoming.
“It will be really exciting to have these medications as a treatment option because right now there’s only one medication, and it’s for people who have pretty advanced fatty liver disease,” said Francavilla. This medication, called resmetirom, is approved by the FDA to target a protein in the liver to reduce fat and inflammation and scarring. But GLP-1s can be used much earlier to prevent the condition.
“With so many cases of MASH happening so much younger, it’s a disease that physicians really need to take seriously,” said Sawhney.
A version of this article appeared on Medscape.com.
Younger People and Long COVID: Underreported, Undertreated
John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.
“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”
The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.
It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.
In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.
“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.
The Impact on Work and Life Productivity
Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”
It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.
Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.
The Financial Strain of Long COVID
For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.
Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).
“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.
He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.
Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.
The Impact of Long COVID on Quality of Life
What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.
“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.
Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.
But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.
A version of this article first appeared on Medscape.com.
John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.
“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”
The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.
It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.
In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.
“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.
The Impact on Work and Life Productivity
Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”
It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.
Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.
The Financial Strain of Long COVID
For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.
Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).
“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.
He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.
Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.
The Impact of Long COVID on Quality of Life
What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.
“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.
Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.
But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.
A version of this article first appeared on Medscape.com.
John Bolecek, 41, of Richmond, Virginia, was diagnosed with long COVID in May of 2022. While his acute infection was mild, once everyone else in his family had recovered, the heavy fatigue he experienced from the start has never lifted.
“When I wake up in the morning, I feel like I haven’t gone to sleep at all,” Bolecek said. “It’s this super fatigue that’s just never gone away.”
The urban planner who once rode his bike to work daily and spent weekends cycling had to quit working and now can barely get through a light walk before long COVID symptoms of post-exertional malaise, an intense fatigue after previously tolerated physical or mental activity, set in. His unrefreshing sleep, fatigue, and dysautonomia — a disruption of the autonomic nervous system that causes dizziness, heart rate changes, and nausea — have made it nearly impossible to share household duties with his wife. She has to do most of the cooking, cleaning, and tending to their two sons, ages 6 and 8 years.
It’s an increasingly familiar story for those hit with long COVID in their prime, a period of life when young and middle-aged adults are the most productive and the busiest, often in the thick of parenting while also taking care of their aging parents. And it’s a group that is among the hardest hit by long COVID both because of the sheer number of patients with the condition and the mental and financial strain that it’s putting on this age group. According to the Centers for Disease Control and Prevention (CDC), 6.9% of adults aged 18-34 years and 8.9% of adults aged 35-49 years have the disorder compared with 4.1% of older adults aged > 65 years who are the least likely to have long COVID.
In a study published recently in Scientific Reports, researchers found that in a population of California residents with long COVID, older individuals (who were sicker to start) had more severe symptoms associated with the condition. But researchers also found that younger people (aged 18-49 years) were more likely to experience symptoms that reduced their productivity and quality of life. They suggested this is both because they have more to do in a given day and because they have a longer life ahead of them living with a chronic condition.
“Much of California’s population falls within the 18-49 age group, [so] we would expect to see the highest overall burden coming from these individuals,” said lead study author Sophie Zhu, a researcher in the Division of Communicable Disease Control at the California Department of Public Health.
The Impact on Work and Life Productivity
Adults and especially those in middle age tend to have a lot of competing stressors during this period of life, said Nisha Viswanathan, MD, director of the UCLA Health Long COVID program. “Patients may need to decrease some of the pressures of life for their health and that can be impossible to do because they have so many other people who are depending on them.”
It’s a different set of circumstances compared with older individuals who may have more severe symptoms because they have underlying conditions. But older Americans are also more likely to be retired and don’t have children who are financially dependent on them. Previous research has shown the burden that long COVID is having on the workforce. A study published in the August 2023 edition of The Lancet Regional Health found that 5.8% of participating patients with long COVID reported occupational changes like moving to part time or remote work, including 1.6% who had completely dropped out of the workforce.
Middle age is also a time of life when patients may not have time to seek the care they need. The chronic nature of long COVID means that treatment can be time consuming and expensive, all of which drains resources from patients who are often supporting spouses, children, and sometimes older parents. A study published in Disability and Health Journal found that patients with long COVID have significantly higher rates of housing instability and financial concerns, such as worries about paying rent or a mortgage, than those without the condition.
The Financial Strain of Long COVID
For those who can’t work, the process of applying for long-term disability can also be complicated. That’s especially true for people whose illness keeps them from doing even basic tasks like filling out paperwork and dealing with disability insurance claims. It requires those applying as a result of their long COVID symptoms to show all records connected to long COVID as well as a medical history, the beginning of their symptoms, and their current treatments.
Even then, many patients complain of having their claims rejected, which can be financially disastrous to families already struggling to get by. Still, experts contend that it’s important to understand that as of July 2021, long COVID is considered a disability under the Americans with Disabilities Act (ADA).
“Long COVID is recognized as a disability under Section 504 of the ADA, and yet day after day, we see violations of the ADA for people with long COVID not getting the accommodations that they need in order to work,” said David Putrino, PhD, the Nash Family director of the Cohen Center for Recovery from Complex Chronic Illness at Mount Sinai in New York City and a renowned expert in long COVID.
He added that short- and long-term disability claims are sometimes denied because of a lack of diagnostic testing to prove a patient has the condition. “This is nonsensical and absurd because the CDC does not require a blood test for the diagnosis of long COVID. It’s at your physician’s discretion,” Putrino said.
Viswanathan agreed. She said that for many of her patients, getting long-term disability has been particularly challenging because there’s no blood test for long COVID to prove patients have the condition. “As a result, for many of our patients, especially when they’re young, they may have to return to work in one form or another,” Viswanathan said.
The Impact of Long COVID on Quality of Life
What’s worse, the full impact is yet unknown because this is likely an underestimated cohort as many of these patients had mild cases of acute COVID-19 and fewer underlying conditions. For others, their long COVID is undiagnosed.
“Much of the impact on productivity and quality of life for this group remains hidden,” said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System in Missouri.
Unfortunately, the impact on Bolecek’s life isn’t so hidden. He can’t work, which has been a financial stressor on the family. He spends much of the day in bed so that he can help with a few things when his wife gets home from work. He can’t cycle anymore and, as a result, has lost many of the friends associated with his favorite hobby.
But he remains hopeful, and more than anything else, he’s thankful for his family. His wife and kids have given him the strength to push on even when the days are hard. “I just don’t know where I’d be without them,” Bolecek said.
A version of this article first appeared on Medscape.com.
New Data: The Most Promising Treatments for Long COVID
Long COVID is a symptom-driven disease, meaning that with no cure, physicians primarily treat the symptoms their patients are experiencing. But as 2024 winds down, researchers have begun to pinpoint a number of treatments that are bringing relief to the 17 million Americans diagnosed with long COVID.
Here’s a current look at what research has identified as some of the most promising treatments.
Low-Dose Naltrexone
Some research suggests that low-dose naltrexone may be helpful for patients suffering from brain fog, pain, sleep issues, and fatigue, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St Louis Health Care System in Missouri.
Low-dose naltrexone is an anti-inflammatory agent currently approved by the Food and Drug Administration for the treatment of alcohol and opioid dependence.
“We don’t know the mechanism for how the medication works, and for that matter, we don’t really understand what causes brain fog. But perhaps its anti-inflammatory properties seem to help, and for some patients, low-dose naltrexone has been helpful,” said Al-Aly.
A March 2024 study found that both fatigue and pain were improved in patients taking low-dose naltrexone. In another study, published in the June 2024 issue of Frontiers in Medicine, researchers found that low-dose naltrexone was associated with improvement of several clinical symptoms related to long COVID such as fatigue, poor sleep quality, brain fog, post-exertional malaise, and headache.
Selective Serotonin Reuptake Inhibitors (SSRIs) and Antidepressants
In 2023, University of Pennsylvania researchers uncovered a link between long COVID and lower levels of serotonin in the body. This helped point to the potential treatment of using SSRIs to treat the condition.
For patients who have overlapping psychiatric issues that go along with brain fog, SSRIs prescribed to treat depression and other mental health conditions, as well as the antidepressant Wellbutrin, have been shown effective at dealing with concentration issues, brain fog, and depression, said Nisha Viswanathan, MD, director of the University of California, Los Angeles (UCLA) Long COVID Program at UCLA Health.
A study published in the November 2023 issue of the journal Scientific Reports found that SSRIs led to a “considerable reduction of symptoms,” especially brain fog, fatigue, sensory overload, and overall improved functioning. Low-dose Abilify, which contains aripiprazole, an antipsychotic medication, has also been found to be effective for cognitive issues caused by long COVID.
“Abilify is traditionally used for the treatment of schizophrenia or other psychotic disorders, but in a low-dose format, there is some data to suggest that it can also be anti-inflammatory and helpful for cognitive issues like brain fog,” said Viswanathan.
Modafinil
Modafinil, a medication previously used for managing narcolepsy, has also been shown effective for the treatment of fatigue and neurocognitive deficits caused by long COVID, said Viswanathan, adding that it’s another medication that she’s found useful for a number of her patients.
It’s thought that these cognitive symptoms are caused by an inflammatory cytokine release that leads to excessive stimulation of neurotransmitters in the body. According to a June 2024 article in the American Journal of Psychiatry, “Modafinil can therapeutically act on these pathways, which possibly contributed to the symptomatic improvement.” But the medication has not been studied widely in patients with long COVID and has been shown to have interactions with other medications.
Metformin
Some research has shown that metformin, a well-known diabetes medication, reduces instances of long COVID when taken during the illness’s acute phase. It seems to boost metabolic function in patients.
“It makes sense that it would work because it seems to have anti-inflammatory effects on the body,” said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland, Ohio. McComsey added that it may reduce the viral persistence that causes some forms of long COVID.
A study published in the October 2023 issue of the journal The Lancet Infectious Diseases found that metformin seemed to reduce instances of long COVID in patients who took it after being diagnosed with acute COVID. It seems less effective in patients who already have long COVID.
Antihistamines
Other data suggest that some patients with long COVID showed improvement after taking antihistamines. Research has shown that long COVID symptoms improved in 29% of patients with long COVID.
While researchers aren’t sure why antihistamines work to quell long COVID, the thought is that, when mast cells, a white blood cell that’s part of the immune system, shed granules and cause an inflammatory reaction, they release a lot of histamines. Antihistamine medications like famotidine block histamine receptors in the body, improving symptoms like brain fog, difficulty breathing, and elevated heart rate in patients.
“For some patients, these can be a lifesaver,” said David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness and a national leader in the treatment of long COVID.
Putrino cautions patients toward taking these and other medications haphazardly without fully understanding that all treatments have risks, especially if they’re taking a number of them.
“Often patients are told that there’s no risk to trying something, but physicians should be counseling their patients and reminding them that there is a risk that includes medication sensitivities and medication interactions,” said Putrino.
The good news is that doctors have begun to identify some treatments that seem to be working in their patients, but we still don’t have the large-scale clinical trials to identify which treatments will work for certain patients and why.
There’s still so much we don’t know, and for physicians on the front lines of treating long COVID, it’s still largely a guessing game. “This is a constellation of symptoms; it’s not just one thing,” said Al-Aly. And while a treatment might be wildly effective for one patient, it might be ineffective or worse, problematic, for another.
A version of this article first appeared on Medscape.com.
Long COVID is a symptom-driven disease, meaning that with no cure, physicians primarily treat the symptoms their patients are experiencing. But as 2024 winds down, researchers have begun to pinpoint a number of treatments that are bringing relief to the 17 million Americans diagnosed with long COVID.
Here’s a current look at what research has identified as some of the most promising treatments.
Low-Dose Naltrexone
Some research suggests that low-dose naltrexone may be helpful for patients suffering from brain fog, pain, sleep issues, and fatigue, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St Louis Health Care System in Missouri.
Low-dose naltrexone is an anti-inflammatory agent currently approved by the Food and Drug Administration for the treatment of alcohol and opioid dependence.
“We don’t know the mechanism for how the medication works, and for that matter, we don’t really understand what causes brain fog. But perhaps its anti-inflammatory properties seem to help, and for some patients, low-dose naltrexone has been helpful,” said Al-Aly.
A March 2024 study found that both fatigue and pain were improved in patients taking low-dose naltrexone. In another study, published in the June 2024 issue of Frontiers in Medicine, researchers found that low-dose naltrexone was associated with improvement of several clinical symptoms related to long COVID such as fatigue, poor sleep quality, brain fog, post-exertional malaise, and headache.
Selective Serotonin Reuptake Inhibitors (SSRIs) and Antidepressants
In 2023, University of Pennsylvania researchers uncovered a link between long COVID and lower levels of serotonin in the body. This helped point to the potential treatment of using SSRIs to treat the condition.
For patients who have overlapping psychiatric issues that go along with brain fog, SSRIs prescribed to treat depression and other mental health conditions, as well as the antidepressant Wellbutrin, have been shown effective at dealing with concentration issues, brain fog, and depression, said Nisha Viswanathan, MD, director of the University of California, Los Angeles (UCLA) Long COVID Program at UCLA Health.
A study published in the November 2023 issue of the journal Scientific Reports found that SSRIs led to a “considerable reduction of symptoms,” especially brain fog, fatigue, sensory overload, and overall improved functioning. Low-dose Abilify, which contains aripiprazole, an antipsychotic medication, has also been found to be effective for cognitive issues caused by long COVID.
“Abilify is traditionally used for the treatment of schizophrenia or other psychotic disorders, but in a low-dose format, there is some data to suggest that it can also be anti-inflammatory and helpful for cognitive issues like brain fog,” said Viswanathan.
Modafinil
Modafinil, a medication previously used for managing narcolepsy, has also been shown effective for the treatment of fatigue and neurocognitive deficits caused by long COVID, said Viswanathan, adding that it’s another medication that she’s found useful for a number of her patients.
It’s thought that these cognitive symptoms are caused by an inflammatory cytokine release that leads to excessive stimulation of neurotransmitters in the body. According to a June 2024 article in the American Journal of Psychiatry, “Modafinil can therapeutically act on these pathways, which possibly contributed to the symptomatic improvement.” But the medication has not been studied widely in patients with long COVID and has been shown to have interactions with other medications.
Metformin
Some research has shown that metformin, a well-known diabetes medication, reduces instances of long COVID when taken during the illness’s acute phase. It seems to boost metabolic function in patients.
“It makes sense that it would work because it seems to have anti-inflammatory effects on the body,” said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland, Ohio. McComsey added that it may reduce the viral persistence that causes some forms of long COVID.
A study published in the October 2023 issue of the journal The Lancet Infectious Diseases found that metformin seemed to reduce instances of long COVID in patients who took it after being diagnosed with acute COVID. It seems less effective in patients who already have long COVID.
Antihistamines
Other data suggest that some patients with long COVID showed improvement after taking antihistamines. Research has shown that long COVID symptoms improved in 29% of patients with long COVID.
While researchers aren’t sure why antihistamines work to quell long COVID, the thought is that, when mast cells, a white blood cell that’s part of the immune system, shed granules and cause an inflammatory reaction, they release a lot of histamines. Antihistamine medications like famotidine block histamine receptors in the body, improving symptoms like brain fog, difficulty breathing, and elevated heart rate in patients.
“For some patients, these can be a lifesaver,” said David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness and a national leader in the treatment of long COVID.
Putrino cautions patients toward taking these and other medications haphazardly without fully understanding that all treatments have risks, especially if they’re taking a number of them.
“Often patients are told that there’s no risk to trying something, but physicians should be counseling their patients and reminding them that there is a risk that includes medication sensitivities and medication interactions,” said Putrino.
The good news is that doctors have begun to identify some treatments that seem to be working in their patients, but we still don’t have the large-scale clinical trials to identify which treatments will work for certain patients and why.
There’s still so much we don’t know, and for physicians on the front lines of treating long COVID, it’s still largely a guessing game. “This is a constellation of symptoms; it’s not just one thing,” said Al-Aly. And while a treatment might be wildly effective for one patient, it might be ineffective or worse, problematic, for another.
A version of this article first appeared on Medscape.com.
Long COVID is a symptom-driven disease, meaning that with no cure, physicians primarily treat the symptoms their patients are experiencing. But as 2024 winds down, researchers have begun to pinpoint a number of treatments that are bringing relief to the 17 million Americans diagnosed with long COVID.
Here’s a current look at what research has identified as some of the most promising treatments.
Low-Dose Naltrexone
Some research suggests that low-dose naltrexone may be helpful for patients suffering from brain fog, pain, sleep issues, and fatigue, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St Louis Health Care System in Missouri.
Low-dose naltrexone is an anti-inflammatory agent currently approved by the Food and Drug Administration for the treatment of alcohol and opioid dependence.
“We don’t know the mechanism for how the medication works, and for that matter, we don’t really understand what causes brain fog. But perhaps its anti-inflammatory properties seem to help, and for some patients, low-dose naltrexone has been helpful,” said Al-Aly.
A March 2024 study found that both fatigue and pain were improved in patients taking low-dose naltrexone. In another study, published in the June 2024 issue of Frontiers in Medicine, researchers found that low-dose naltrexone was associated with improvement of several clinical symptoms related to long COVID such as fatigue, poor sleep quality, brain fog, post-exertional malaise, and headache.
Selective Serotonin Reuptake Inhibitors (SSRIs) and Antidepressants
In 2023, University of Pennsylvania researchers uncovered a link between long COVID and lower levels of serotonin in the body. This helped point to the potential treatment of using SSRIs to treat the condition.
For patients who have overlapping psychiatric issues that go along with brain fog, SSRIs prescribed to treat depression and other mental health conditions, as well as the antidepressant Wellbutrin, have been shown effective at dealing with concentration issues, brain fog, and depression, said Nisha Viswanathan, MD, director of the University of California, Los Angeles (UCLA) Long COVID Program at UCLA Health.
A study published in the November 2023 issue of the journal Scientific Reports found that SSRIs led to a “considerable reduction of symptoms,” especially brain fog, fatigue, sensory overload, and overall improved functioning. Low-dose Abilify, which contains aripiprazole, an antipsychotic medication, has also been found to be effective for cognitive issues caused by long COVID.
“Abilify is traditionally used for the treatment of schizophrenia or other psychotic disorders, but in a low-dose format, there is some data to suggest that it can also be anti-inflammatory and helpful for cognitive issues like brain fog,” said Viswanathan.
Modafinil
Modafinil, a medication previously used for managing narcolepsy, has also been shown effective for the treatment of fatigue and neurocognitive deficits caused by long COVID, said Viswanathan, adding that it’s another medication that she’s found useful for a number of her patients.
It’s thought that these cognitive symptoms are caused by an inflammatory cytokine release that leads to excessive stimulation of neurotransmitters in the body. According to a June 2024 article in the American Journal of Psychiatry, “Modafinil can therapeutically act on these pathways, which possibly contributed to the symptomatic improvement.” But the medication has not been studied widely in patients with long COVID and has been shown to have interactions with other medications.
Metformin
Some research has shown that metformin, a well-known diabetes medication, reduces instances of long COVID when taken during the illness’s acute phase. It seems to boost metabolic function in patients.
“It makes sense that it would work because it seems to have anti-inflammatory effects on the body,” said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland, Ohio. McComsey added that it may reduce the viral persistence that causes some forms of long COVID.
A study published in the October 2023 issue of the journal The Lancet Infectious Diseases found that metformin seemed to reduce instances of long COVID in patients who took it after being diagnosed with acute COVID. It seems less effective in patients who already have long COVID.
Antihistamines
Other data suggest that some patients with long COVID showed improvement after taking antihistamines. Research has shown that long COVID symptoms improved in 29% of patients with long COVID.
While researchers aren’t sure why antihistamines work to quell long COVID, the thought is that, when mast cells, a white blood cell that’s part of the immune system, shed granules and cause an inflammatory reaction, they release a lot of histamines. Antihistamine medications like famotidine block histamine receptors in the body, improving symptoms like brain fog, difficulty breathing, and elevated heart rate in patients.
“For some patients, these can be a lifesaver,” said David Putrino, the Nash Family Director of the Cohen Center for Recovery from Complex Chronic Illness and a national leader in the treatment of long COVID.
Putrino cautions patients toward taking these and other medications haphazardly without fully understanding that all treatments have risks, especially if they’re taking a number of them.
“Often patients are told that there’s no risk to trying something, but physicians should be counseling their patients and reminding them that there is a risk that includes medication sensitivities and medication interactions,” said Putrino.
The good news is that doctors have begun to identify some treatments that seem to be working in their patients, but we still don’t have the large-scale clinical trials to identify which treatments will work for certain patients and why.
There’s still so much we don’t know, and for physicians on the front lines of treating long COVID, it’s still largely a guessing game. “This is a constellation of symptoms; it’s not just one thing,” said Al-Aly. And while a treatment might be wildly effective for one patient, it might be ineffective or worse, problematic, for another.
A version of this article first appeared on Medscape.com.
The Push to Get More People Into Long COVID Studies
When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone.
Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco.
For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.
That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.
“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
It’s Not the Number of Studies, It’s Navigating Them
In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.
“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up.
Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas.
According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland.
Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
Too Many Barriers to Entry
A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.
Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote.
“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”
Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere.
Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco.
“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials.
Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins.
“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
Long Fight for Better Long COVID Research
For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues.
He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.
His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.
“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”
A version of this article first appeared on Medscape.com.
When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone.
Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco.
For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.
That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.
“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
It’s Not the Number of Studies, It’s Navigating Them
In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.
“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up.
Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas.
According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland.
Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
Too Many Barriers to Entry
A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.
Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote.
“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”
Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere.
Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco.
“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials.
Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins.
“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
Long Fight for Better Long COVID Research
For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues.
He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.
His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.
“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”
A version of this article first appeared on Medscape.com.
When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone.
Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco.
For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.
That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.
“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
It’s Not the Number of Studies, It’s Navigating Them
In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.
“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up.
Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas.
According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland.
Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
Too Many Barriers to Entry
A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.
Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote.
“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”
Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere.
Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco.
“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials.
Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins.
“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
Long Fight for Better Long COVID Research
For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues.
He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.
His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.
“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”
A version of this article first appeared on Medscape.com.
4 Years In, a Sobering Look at Long COVID Progress
Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)
What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.
Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.
Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.
While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.
Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.
Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.
Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.
Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.
Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
Promising Treatments Have Emerged
Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.
Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.
“This is something tangible that we can offer to patients,” she said.
Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.
For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.
“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.
Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.
Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.
It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
Clinical Trials Exploring New Therapies
Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.
Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.
Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.
Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.
She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
Lack of Urgency Holds Back Progress
Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.
“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.
Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.
He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.
“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”
A version of this article first appeared on Medscape.com.
Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)
What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.
Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.
Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.
While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.
Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.
Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.
Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.
Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.
Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
Promising Treatments Have Emerged
Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.
Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.
“This is something tangible that we can offer to patients,” she said.
Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.
For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.
“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.
Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.
Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.
It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
Clinical Trials Exploring New Therapies
Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.
Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.
Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.
Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.
She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
Lack of Urgency Holds Back Progress
Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.
“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.
Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.
He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.
“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”
A version of this article first appeared on Medscape.com.
Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)
What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.
Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.
Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.
While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.
Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.
Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.
Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.
Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.
Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
Promising Treatments Have Emerged
Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.
Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.
“This is something tangible that we can offer to patients,” she said.
Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.
For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.
“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.
Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.
Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.
It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
Clinical Trials Exploring New Therapies
Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.
Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.
Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.
Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.
She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
Lack of Urgency Holds Back Progress
Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.
“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.
Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.
He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.
“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”
A version of this article first appeared on Medscape.com.
New Evidence Suggests Long COVID Could Be a Brain Injury
Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating.
Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.
The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
Brain Deficits Equal to 20 Years of Brain Aging
As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.
Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.
The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.
“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations
Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic.
“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”
Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
How Do COVID-Related Brain Injuries Happen?
Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.
Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.
The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson.
He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
A New Path Forward
Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.
There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.”
“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
Still More to Learn
In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus.
For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need.
What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.
“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.
A version of this article appeared on Medscape.com.
Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating.
Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.
The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
Brain Deficits Equal to 20 Years of Brain Aging
As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.
Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.
The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.
“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations
Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic.
“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”
Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
How Do COVID-Related Brain Injuries Happen?
Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.
Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.
The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson.
He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
A New Path Forward
Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.
There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.”
“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
Still More to Learn
In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus.
For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need.
What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.
“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.
A version of this article appeared on Medscape.com.
Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating.
Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.
The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
Brain Deficits Equal to 20 Years of Brain Aging
As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.
Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.
The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.
“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations
Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic.
“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”
Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
How Do COVID-Related Brain Injuries Happen?
Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.
Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.
The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson.
He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
A New Path Forward
Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.
There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.”
“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
Still More to Learn
In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus.
For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need.
What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.
“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.
A version of this article appeared on Medscape.com.
Five Bold Predictions for Long COVID in 2024
With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.
Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.
#1: We’ll gain a better understanding of each long COVID phenotype
This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.
Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.
Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.
Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.
“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.
#2: Monoclonal antibodies may change the game
We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.
Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.
Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.
#3: Paxlovid could prove effective for long COVID
The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.
In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.
Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.
It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.
#4: Anti-inflammatories like metformin could prove useful
Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.
The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.
“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”
Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.
Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.
#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID
One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.
Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.
Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.
If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.
A version of this article appeared on Medscape.com.
With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.
Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.
#1: We’ll gain a better understanding of each long COVID phenotype
This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.
Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.
Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.
Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.
“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.
#2: Monoclonal antibodies may change the game
We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.
Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.
Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.
#3: Paxlovid could prove effective for long COVID
The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.
In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.
Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.
It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.
#4: Anti-inflammatories like metformin could prove useful
Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.
The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.
“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”
Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.
Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.
#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID
One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.
Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.
Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.
If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.
A version of this article appeared on Medscape.com.
With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.
Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.
#1: We’ll gain a better understanding of each long COVID phenotype
This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.
Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.
Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.
Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.
“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.
#2: Monoclonal antibodies may change the game
We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.
Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.
Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.
“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.
#3: Paxlovid could prove effective for long COVID
The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.
In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.
Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.
It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.
#4: Anti-inflammatories like metformin could prove useful
Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.
The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.
“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”
Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.
Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.
#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID
One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.
Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.
Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said last month in an interview with this news organization.
If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.
A version of this article appeared on Medscape.com.
New tests may finally diagnose long COVID
One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But
Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.
Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.
Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.
In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.
“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.”
The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2.
In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.
“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health.
Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.
Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.
It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems.
“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease.
Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID.
These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus.
The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said.
Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.
A version of this article first appeared on Medscape.com.
One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But
Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.
Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.
Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.
In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.
“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.”
The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2.
In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.
“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health.
Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.
Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.
It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems.
“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease.
Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID.
These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus.
The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said.
Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.
A version of this article first appeared on Medscape.com.
One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But
Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.
Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.
Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.
In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.
“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.”
The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2.
In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.
“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health.
Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.
Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.
It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems.
“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease.
Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID.
These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus.
The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said.
Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.
A version of this article first appeared on Medscape.com.
FROM MEDRXIV
A new long COVID explanation: Low serotonin levels?
Could antidepressants hold the key to treating long COVID? The study even points to a possible treatment.
Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.
Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.
Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.
Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.
The hope is that this study could have implications for new treatments, he said.
“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.
Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.
His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.
The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.
“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.
Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.
Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.
Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.
Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.
David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.
But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.
“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.
What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.
Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.
“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.
Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.
The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.
Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.
Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.
“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”
A version of this article first appeared on Medscape.com.
Could antidepressants hold the key to treating long COVID? The study even points to a possible treatment.
Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.
Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.
Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.
Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.
The hope is that this study could have implications for new treatments, he said.
“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.
Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.
His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.
The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.
“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.
Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.
Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.
Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.
Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.
David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.
But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.
“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.
What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.
Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.
“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.
Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.
The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.
Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.
Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.
“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”
A version of this article first appeared on Medscape.com.
Could antidepressants hold the key to treating long COVID? The study even points to a possible treatment.
Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.
Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.
Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.
Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.
The hope is that this study could have implications for new treatments, he said.
“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.
Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.
His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.
The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.
“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.
Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.
Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.
Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.
“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.
Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.
David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.
But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.
“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.
What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.
Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.
“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.
Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.
The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.
Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.
Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.
“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”
A version of this article first appeared on Medscape.com.
FROM CELL
Long COVID ‘brain fog’ confounds doctors, but new research offers hope
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.
Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.
She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.
Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.
Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.
“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”
Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.
Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.
In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.
She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.
Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.
“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.
Additionally, ABI is an actual diagnosis, whereas brain fog is not.
“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.
Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.
Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.
Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.
Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.
“The COVID virus is very invasive to the brain,” Dr. Bell said.
Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.
Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.
Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.
Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.
“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.
Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.
But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.
“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”
A version of this article first appeared on Medscape.com.