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Hospital programs tackle mental health effects of long COVID
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID. 
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID.
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
There’s little doubt that long COVID is real. Even as doctors and federal agencies struggle to define the syndrome, hospitals and health care systems are opening long COVID specialty treatment programs. As of July 25, there’s at least one long COVID center in almost every state – 48 out of 50, according to the patient advocacy group Survivor Corps.
Among the biggest challenges will be treating the mental health effects of long COVID.
Specialized centers will be tackling these problems even as the United States struggles to deal with mental health needs.
One study of COVID patients found more than one-third of them had symptoms of depression, anxiety, or PTSD 3-6 months after their initial infection. Another analysis of 30 previous studies of long COVID patients found roughly one in eight of them had severe depression – and that the risk was similar regardless of whether people were hospitalized for COVID-19.
“Many of these symptoms can emerge months into the course of long COVID illness,” said Jordan Anderson, DO, a neuropsychiatrist who sees patients at the Long COVID-19 Program at Oregon Health & Science University, Portland. Psychological symptoms are often made worse by physical setbacks like extreme fatigue and by challenges of working, caring for children, and keeping up with daily routines, he said.
“This impact is not only severe, but also chronic for many,” he said.
Like dozens of hospitals around the country, Oregon Health & Science opened its center for long COVID as it became clear that more patients would need help for ongoing physical and mental health symptoms. Today, there’s at least one long COVID center – sometimes called post-COVID care centers or clinics – in every state but Kansas and South Dakota, Survivor Corps said.
Many long COVID care centers aim to tackle both physical and mental health symptoms, said Tracy Vannorsdall, PhD, a neuropsychologist with the Johns Hopkins Post-Acute COVID-19 Team program. One goal at Hopkins is to identify patients with psychological issues that might otherwise get overlooked.
A sizable minority of patients at the Johns Hopkins center – up to about 35% – report mental health problems that they didn’t have until after they got COVID-19, Dr. Vannorsdall says. The most common mental health issues providers see are depression, anxiety, and trauma-related distress.
“Routine assessment is key,” Dr. Vannorsdall said. “If patients are not asked about their mental health symptoms, they may not spontaneously report them to their provider due to fear of stigma or simply not appreciating that there are effective treatments available for these issues.”
Fear that doctors won’t take symptoms seriously is common, says Heather Murray MD, a senior instructor in psychiatry at the University of Colorado at Denver, Aurora.
“Many patients worry their physicians, loved ones, and society will not believe them or will minimize their symptoms and suffering,” said Dr. Murray, who treats patients at the UCHealth Post-COVID Clinic.
Diagnostic tests in long COVID patients often don’t have conclusive results, which can lead doctors and patients themselves to question whether symptoms are truly “physical versus psychosomatic,” she said. “It is important that providers believe their patients and treat their symptoms, even when diagnostic tests are unrevealing.”
Growing mental health crisis
Patients often find their way to academic treatment centers after surviving severe COVID-19 infections. But a growing number of long COVID patients show up at these centers after milder cases. These patients were never hospitalized for COVID-19 but still have persistent symptoms like fatigue, thinking problems, and mood disorders.
Among the major challenges is a shortage of mental health care providers to meet the surging need for care since the start of the pandemic. Around the world, anxiety and depression surged 25% during the first year of the pandemic, according to the World Health Organization.
In the United States, 40% of adults report feelings of anxiety and depression, and one in three high school students have feelings of sadness and hopelessness, according to a March 2022 statement from the White House.
Despite this surging need for care, almost half of Americans live in areas with a severe shortage of mental health care providers, according to the Health Resources and Services Administration. As of 2019, the United States had a shortage of about 6,790 mental health providers. Since then, the shortage has worsened; it’s now about 7,500 providers.
“One of the biggest challenges for hospitals and clinics in treating mental health disorders in long COVID is the limited resources and long wait times to get in for evaluations and treatment,” said Nyaz Didehbani, PhD, a neuropsychologist who treats long COVID patients at the COVID Recover program at the University of Texas Southwestern Medical Center, Dallas.
These delays can lead to worse outcomes, Dr. Didehbani said. “Additionally, patients do not feel that they are being heard, as many providers are not aware of the mental health impact and relationship with physical and cognitive symptoms.” .
Even when doctors recognize that psychological challenges are common with long COVID, they still have to think creatively to come up with treatments that meet the unique needs of these patients, said Thida Thant, MD, an assistant professor of psychiatry at the University of Colorado who treats patients at the UCHealth Post-COVID Clinic.
“There are at least two major factors that make treating psychological issues in long COVID more complex: The fact that the pandemic is still ongoing and still so divisive throughout society, and the fact that we don’t know a single best way to treat all symptoms of long COVID,” she said.
Some common treatments for anxiety and depression, like psychotherapy and medication, can be used for long COVID patients with these conditions. But another intervention that can work wonders for many people with mood disorders – exercise – doesn’t always work for long COVID patients. That’s because many of them struggle with physical challenges like chronic fatigue and what’s known as postexertional malaise, or a worsening of symptoms after even limited physical effort.
“While we normally encourage patients to be active, have a daily routine, and to engage in physical activity as part of their mental health treatment, some long COVID patients find that their symptoms worsen after increased activity,” Dr. Vannorsdall said.
Patients who are able to reach long COVID care centers are much more apt to get mental health problems diagnosed and treated, doctors at many programs around the country agree. But many patients hardest hit by the pandemic – the poor and racial and ethnic minorities – are also less likely to have ready access to hospitals that offer these programs, said Dr. Anderson.
“Affluent, predominantly White populations are showing up in these clinics, while we know that non-White populations have disproportionally high rates of acute infection, hospitalization, and death related to the virus,” he said.
Clinics are also concentrated in academic medical centers and in urban areas, limiting options for people in rural communities who may have to drive for hours to access care, Dr. Anderson said.
“Even before long COVID, we already knew that many people live in areas where there simply aren’t enough mental health services available,” said John Zulueta, MD, an assistant professor of clinical psychiatry at the University of Illinois at Chicago who provides mental health evaluations at the UI Health Post-COVID Clinic.
“As more patients develop mental health issues associated with long COVID, it’s going to put more stress on an already stressed system,” he said.
A version of this article first appeared on WebMD.com.
Science lags behind for kids with long COVID
Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.
The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.
“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.
Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.
“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”
Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.
For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.
“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.
Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.
Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.
Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.
“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”
It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.
The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.
“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.
There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.
“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.
As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.
“For the first time in months, I was feeling like myself again,” she said.
But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.
“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.
She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.
For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.
“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”
Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.
“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”
A version of this article first appeared on WebMD.com.
Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.
The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.
“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.
Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.
“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”
Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.
For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.
“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.
Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.
Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.
Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.
“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”
It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.
The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.
“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.
There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.
“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.
As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.
“For the first time in months, I was feeling like myself again,” she said.
But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.
“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.
She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.
For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.
“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”
Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.
“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”
A version of this article first appeared on WebMD.com.
Emma Sherman, a 13-year-old girl in Ascot, England, woke up to a dizzying aura of blind spots and flashing lights in her field of vision. It was May 2020, and she also had crippling nausea and headaches. By August, her dizziness was so overwhelming, she couldn’t hold her head up, lying in her mother’s lap for hours, too fatigued to attend school.
The former competitive gymnast, who had hoped to try out for the cheerleading squad, now used a wheelchair and was a shadow of her former self. She had been diagnosed with COVID-induced postural orthostatic tachycardia syndrome, a condition often caused by an infection that results in a higher heart rate, extreme nausea, dizziness, and fatigue.
“I was so into sports before I got long COVID, and afterwards I could barely walk,” Emma said.
Even minor movements sent her heart rate sky-high. Her long chestnut hair turned gray and fell out in clumps. In the hospital, she was pricked and prodded, her blood tested for numerous conditions.
“They ran every scan known to man and took an MRI of her brain,” said Emma’s mother, Marie Sherman. “All was clear.”
Emma’s pediatrician determined that the teen had long COVID after having had a mild case of the virus in March, about 2 months before her puzzling symptoms began. But beyond a positive antibody test, doctors have found little evidence of what was causing Emma’s symptoms.
For Emma and others with long COVID, there are no medications shown to directly target the condition. Instead, caregivers target their symptoms, which include nausea, dizziness, fatigue, headaches, and a racing heart, said Laura Malone, MD, codirector of the Johns Hopkins Kennedy Krieger Pediatric Post–COVID-19 Rehabilitation Clinic in Baltimore.
“Right now, it’s a rehabilitation-based approach focused on improving symptoms and functioning so that kids can go back to their usual activities as much as possible,” she says.
Depression and anxiety are common, although doctors are struggling to figure out whether COVID is changing the brain or whether mental health symptoms result from all the life disruptions. There’s little research to show how may kids have depression because of long COVID. Dr. Malone said about half of her patients at the Kennedy Krieger Institute›s long COVID clinic are also dealing with mental health issues.
Patients with headaches, dizziness, and nausea are given pain and nausea medications and recommendations for a healthy diet with added fruits and vegetables, monounsaturated fats, lower sodium, unprocessed foods, and whole grains. Kids with irregular or racing heart rates are referred to cardiologists and potentially prescribed beta-blockers to treat their heart arrhythmias, while children with breathing problems may be referred to pulmonologists and those with depression to a psychiatrist.
Still, many patients like Emma go to their doctors with phantom symptoms that don’t show up on scans or blood tests.
“We’re not seeing any evidence of structural damage to the brain, for example,” said Dr. Malone. “When we do MRIs, they often come out normal.”
It’s possible that the virus lingers in some patients, said Rajeev Fernando, MD, an infectious disease specialist and a fellow at Harvard Medical School, Boston. Kids’ strong immune systems often fend off problems that can be noticed. But on the inside, dead fragments of the virus persist, floating in hidden parts of the body and activating the immune system long after the threat has passed.
The virus can be in the gut and in the brain, which may help explain why symptoms like brain fog and nausea can linger in children.
“The immune system doesn’t recognize whether fragments of the virus are dead or alive. It continues to think it’s fighting active COVID,” said Dr. Fernando.
There is little data on how long symptoms last, Dr. Fernando said, as well as how many kids get them and why some are more vulnerable than others. Some research has found that about 5%-15% of children with COVID may get long COVID, but the statistics vary globally.
“Children with long COVID have largely been ignored. And while we’re talking about it now, we’ve got some work to do,” said Dr. Fernando.
As for Emma, she recovered in January of 2021, heading back to school and her friends, although her cardiologist advised her to skip gym classes.
“For the first time in months, I was feeling like myself again,” she said.
But the coronavirus found its way to Emma again. Although she was fully vaccinated in the fall of 2021, when the Omicron variant swept the world late that year, she was infected again.
“When the wave of Omicron descended, Emma was like a sitting duck,” her mother said.
She was bedridden with a high fever and cough. The cold-like symptoms eventually went away, but the issues in her gut stuck around. Since then, Emma has had extreme nausea, losing most of the weight she had gained back.
For her part, Ms. Sherman has found solace in a group called Long COVID Kids, a nonprofit in Europe and the United States. The group is raising awareness about the condition in kids to increase funding, boost understanding, and improve treatment and outcomes.
“There’s nothing worse than watching your child suffer and not being able to do anything about it,” she said. “I tell Emma all the time: If I could just crawl in your body and take it, I would do it in a second.”
Emma is hoping for a fresh start with her family’s move in the coming weeks to Sotogrande in southern Spain.
“I miss the simplest things like going for a run, going to the fair with my friends, and just feeling well,” she said. “I have a long list of things I’ll do once this is all done.”
A version of this article first appeared on WebMD.com.
Body-brain neuroinflammation loop may cause chronic ME/CFS, long COVID symptoms
ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.
What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.
“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.
Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”
Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.
This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
Lingering inflammation may be the culprit
Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.
“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”
While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.
While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.
“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.
Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.
However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.
“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.
This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.
ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.
What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.
“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.
Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”
Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.
This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
Lingering inflammation may be the culprit
Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.
“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”
While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.
While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.
“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.
Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.
However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.
“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.
This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.
ME/CFS has been established as resulting from infections, environmental exposures, stressors, and surgery. Similarities have been drawn during the COVID-19 pandemic between ME/CFS and a large subgroup of patients with post-acute sequelae of SARS-CoV-2 infection – also known as post-COVID conditions, or long COVID – who continue to have viral fatigue and other lingering symptoms after their infection resolves.
What has been less clearly understood, the researchers said, is the reason behind why ME/CFS and other postviral fatigue tends to be chronic and can sometime develop into a lifelong condition.
“These diseases are very closely related, and it is clear the biological basis of long COVID is unequivocally connected to the original COVID infection – so there should no longer be any debate and doubt about the fact that postviral fatigue syndromes like ME/CFS are biologically based and involve much disturbed physiology,” Warren Tate, MSc, PhD, emeritus professor in the department of biochemistry at the University of Otago in Dunedin, New Zealand, stated in a press release.
Their hypothesis, set forth in a study published in Frontiers of Neurology, proposes that the systemic immune/inflammatory response that occurs after an infection or stressful event does not revolve, which results in a “fluctuating chronic neuroinflammation that sustains and controls the complex neurological symptoms of ME/CFS and long COVID and facilitates frequent more serious relapses in response to life stress, as evidenced from a comprehensive disruption to the cellular molecular biology and body’s physiological pathways.”
Dr. Tate and colleagues said that it is still unclear how the neuroinflammation occurs, why it’s persistent in ME/CFS, and how it causes symptoms associated with ME/CFS. In their hypothesis, “abnormal signaling or transport of molecules/cells occurs through one or both of neurovascular pathways and/or a dysfunctional blood brain barrier,” they said, noting “the normally separate and contained brain/CNS compartment in the healthy person becomes more porous.” The neurological symptoms associated with ME/CFS occur due to strong signals sent because of persistent “inflammatory signals or immune cells/molecules migrating into the brain,” they explained.
This results in a continuous loop where the central nervous system sends signals back to the body through the hypothalamus/paraventricular nucleus and the brain stem. “The resulting symptoms and the neurologically driven ‘sickness response’ for the ME/CFS patient would persist, preventing healing and a return to the preinfectious/stress-related state,” Dr. Tate and colleagues said.
Lingering inflammation may be the culprit
Commenting on the study, Achillefs Ntranos, MD, a board-certified neurologist in private practice in Scarsdale, N.Y., who was not involved with the research, said previous studies have shown that long COVID is linked to chronic activation of microglia in the brain, which has also been seen to activate in patients with ME/CFS.
“The hypothesis that lingering inflammation in the brain is the culprit behind the neurological symptoms of long COVID and ME/CFS is valid,” he said. “If these cells remain activated in the brain, they can cause a state of increased and lingering inflammation, which can interfere with the function of neurons, thus producing neurological symptoms. Since the neurological symptoms are similar between these entities, the mechanisms that produce them might also be similar.”
While the exact cause of ME/CFS is still unclear, it is often tied to the aftereffects of a flu-like illness, Dr. Ntranos said. “This has led researchers to propose that it arises after a viral infection, with many different types of viruses being associated with it. Other ways researchers think ME/CFS is being brought on after a viral illness is via changes in the immune system, such as chronic production of cytokines, neuroinflammation, and disruption of the hypothalamic-pituitary-adrenal axis, which regulates the body’s response to stress,” he explained.
While a newer condition, long COVID is not all that different from ME/CFS, Dr. Ntranos noted, sharing the catalyst of a viral infection and core neurological symptoms such as fatigue, postexertional malaise, a “brain fog” that makes thinking or concentrating difficult, sleep problems, and lightheadedness, but there are differences that set it apart from ME/CFS.
“Long COVID is unique in having additional symptoms that are specific to the SARS-CoV-2 virus, such as respiratory and cardiovascular symptoms and loss of smell and taste. However most central nervous system effects are the same between these two entities,” he said.
Dr. Ntranos said long COVID’s neurological symptoms are similar to that of multiple sclerosis (MS), such as “brain fog” and postexertional malaise. “Since MS only affects the brain and spinal cord, there are no symptoms from other organ systems, such as the lungs, heart, or digestive system, contrary to long COVID. Furthermore, MS rarely affects smell and taste, making these symptoms unique to COVID,” he said.
However, he pointed out that brain fog and fatigue symptoms on their own can be nonspecific and attributed to many different conditions, such as obstructive sleep apnea, migraines, depression, anxiety, thyroid problems, vitamin deficiencies, dehydration, sleep disorders, and side effects of medications.
“More research needs to be done to understand how these cells are being activated, how they interfere with neuronal function, and why they remain in that state in some people, who then go on to develop fatigue and brain fog,” he said.
This study was funded by the Healthcare Otago Charitable Trust, the Associated New Zealand Myalgic Encephalomyelitis Society, and donations from families of patients with ME/CFS. The authors and Dr. Ntranos report no relevant financial disclosures.
FROM FRONTIERS IN NEUROLOGY
Immune response may explain brain damage after COVID-19
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
It seems that the virus does not infect the brain directly. The scientists found evidence that antibodies – proteins produced by the immune system in response to viruses and other invaders – are involved in an attack on the cells lining the brain’s blood vessels, leading to inflammation and damage. The study was published in the journal Brain.
Brain tissue autopsy
“Patients often develop neurological complications with COVID-19, but the underlying pathophysiological process is not well understood,” Avindra Nath, MD, stated in a National Institutes of Health news release. Dr. Nath, who specializes in neuroimmunology, is the clinical director at the National Institute of Neurological Disorders and Stroke (NINDS) and the senior author of the study. “We had previously shown blood vessel damage and inflammation in patients’ brains at autopsy, but we didn’t understand the cause of the damage. I think in this paper we’ve gained important insight into the cascade of events.”
In this study, Dr. Nath and his team examined brain tissue from a subset of patients from their previous study. The nine individuals, ages 24-73 years, died shortly after contracting COVID-19. They were chosen because structural brain scans showed signs of blood vessel damage in the brain. The samples were compared with those from 10 controls. The team looked at neuroinflammation and immune responses using immunohistochemistry.
As in their earlier study, researchers found signs of leaky blood vessels based on the presence of blood proteins that normally do not cross the blood-brain barrier. This suggests that the tight junctions between the endothelial cells in the blood-brain barrier have been damaged.
Neurologic symptoms’ molecular basis
Dr. Nath and his colleagues discovered deposits of immune complexes on the surface of the cells. This finding is evidence that damage to endothelial cells was likely due to an immune response.
These observations suggest an antibody-mediated attack that activates endothelial cells. When endothelial cells are activated, they express proteins called adhesion molecules that cause platelets to stick together.
“Activation of the endothelial cells brings platelets that stick to the blood vessel walls, causing clots to form and leakage to occur. At the same time, the tight junctions between the endothelial cells get disrupted, causing them to leak,” Dr. Nath explained. “Once leakage occurs, immune cells such as macrophages may come to repair the damage, setting up inflammation. This, in turn, causes damage to neurons.”
Researchers found that in areas with damage to the endothelial cells, more than 300 genes showed decreased expression, whereas six genes were increased. These genes were associated with oxidative stress, DNA damage, and metabolic dysregulation. As the NIH news release notes, this may provide clues to the molecular basis of neurologic symptoms related to COVID-19 and offer potential therapeutic targets.
Together, these findings give insight into the immune response damaging the brain after COVID-19 infection. But it remains unclear what antigen the immune response is targeting, because the virus itself was not detected in the brain. It is possible that antibodies against the SARS-CoV-2 spike protein could bind to the angiotensin-converting enzyme 2 receptor used by the virus to enter cells. More research is needed to explore this hypothesis.
‘Brain fog’ explained?
The study may also have implications for understanding and treating long-term neurologic symptoms after COVID-19, which include headache, fatigue, loss of taste and smell, sleep problems, and “brain fog.” Had the patients in the study survived, the researchers believe they would likely have developed long COVID.
“It is quite possible that this same immune response persists in long COVID patients, resulting in neuronal injury,” said Dr. Nath. “There could be a small, indolent immune response that is continuing, which means that immune-modulating therapies might help these patients. So, these findings have very important therapeutic implications.”
The results suggest that treatments designed to prevent the development of the immune complexes observed in the study could be potential therapies for post-COVID neurologic symptoms.
This study was supported by the NINDS Division of Intramural Research (NS003130) and K23NS109284, the Roy J. Carver Foundation, and the Iowa Neuroscience Institute.
A version of this article first appeared on Medscape.com. This article was translated from Medscape French edition.
Does your patient have long COVID? Some clues on what to look for
New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.
“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.
Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.
Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.
Unfortunately, there’s no easy way to screen for long COVID.
“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”
It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
What to look for
Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”
More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.
“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.
This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.
“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.
Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.
One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:
- Headache.
- Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
- Dizziness when standing.
- Pins-and-needles feelings.
- Changes in smell or taste.
- Depression or anxiety.
You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
Risk of having other health conditions
People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:
- Type 2 diabetes.
- Kidney failure.
- Pulmonary embolism, or a blood clot in the lung.
- Myocarditis, an inflamed heart.
While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.
“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.
COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
Is it long COVID or something else?
Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.
They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.
“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.
What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.
“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”
Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”
A version of this article first appeared on WebMD.com.
New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.
“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.
Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.
Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.
Unfortunately, there’s no easy way to screen for long COVID.
“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”
It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
What to look for
Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”
More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.
“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.
This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.
“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.
Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.
One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:
- Headache.
- Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
- Dizziness when standing.
- Pins-and-needles feelings.
- Changes in smell or taste.
- Depression or anxiety.
You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
Risk of having other health conditions
People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:
- Type 2 diabetes.
- Kidney failure.
- Pulmonary embolism, or a blood clot in the lung.
- Myocarditis, an inflamed heart.
While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.
“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.
COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
Is it long COVID or something else?
Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.
They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.
“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.
What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.
“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”
Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”
A version of this article first appeared on WebMD.com.
New Yorker Lyss Stern came down with COVID-19 at the beginning of the pandemic, in March 2020. She ran a 103° F fever for 5 days straight and was bedridden for several weeks. Yet symptoms such as a persistent headache and tinnitus, or ringing in her ears, lingered.
“Four months later, I still couldn’t walk four blocks without becoming winded,” says Ms. Stern, 48. Five months after her diagnosis, her doctors finally gave a name to her condition: long COVID.
Long COVID is known by many different names: long-haul COVID, postacute COVID-19, or even chronic COVID. It’s a general term used to describe the range of ongoing health problems people can have after their infection.
Another earlier report found that one in five COVID-19 survivors between the ages of 18 and 64, and one in four survivors aged at least 65, have a health condition that may be related to their previous bout with the virus.
Unfortunately, there’s no easy way to screen for long COVID.
“There’s no definite laboratory test to give us a diagnosis,” says Daniel Sterman, MD, director of the division of pulmonary, critical care and sleep medicine at NYU Langone Health in New York. “We’re also still working on a definition, since there’s a whole slew of symptoms associated with the condition.”
It’s a challenge that Ms. Stern is personally acquainted with after she bounced from doctor to doctor for several months before she found her way to the Center for Post-COVID Care at Mount Sinai Hospital in New York. “It was a relief to have an official diagnosis, even if it didn’t bring immediate answers,” she says.
What to look for
Many people who become infected with COVID-19 get symptoms that linger for 2-3 weeks after their infection has cleared, says Brittany Baloun, a certified nurse practitioner at the Cleveland Clinic. “It’s not unusual to feel some residual shortness of breath or heart palpitations, especially if you are exerting yourself,” she says. “The acute phase of COVID itself can last for up to 14 days. But if it’s been 30 days since you came down with the virus, and your symptoms are still there and not improving, it indicates some level of long COVID.”
More than 200 symptoms can be linked to long COVID. But perhaps the one that stands out the most is constant fatigue that interferes with daily life.
“We often hear that these patients can’t fold the laundry or take a short walk with their dog without feeling exhausted,” Ms. Baloun says.
This exhaustion may get worse after patients exercise or do something mentally taxing, a condition known as postexertional malaise.
“It can be crushing fatigue; I may clean my room for an hour and talk to a friend, and the next day feel like I can’t get out of bed,” says Allison Guy, 36, who was diagnosed with COVID in February 2021. She’s now a long-COVID advocate in Washington.
Other symptoms can be divided into different categories, which include cardiac/lung symptoms such as shortness of breath, coughing, chest pain, and heart palpitations, as well as neurologic symptoms.
One of the most common neurologic symptoms is brain fog, says Andrew Schamess, MD, a professor of internal medicine at Ohio State University Wexner Medical Center, Columbus, who runs its post-COVID recovery program. “Patients describe feeling ‘fuzzy’ or ‘spacey,’ and often report that they are forgetful or have memory problems,” he says. Others include:
- Headache.
- Sleep problems. One 2022 study from the Cleveland Clinic found that more than 40% of patients with long COVID reported sleep disturbances.
- Dizziness when standing.
- Pins-and-needles feelings.
- Changes in smell or taste.
- Depression or anxiety.
You could also have digestive symptoms such as diarrhea or stomach pain. Other symptoms include joint or muscle pain, rashes, or changes in menstrual cycles.
Risk of having other health conditions
People who have had COVID-19, particularly a severe case, may be more at risk of getting other health conditions, such as:
- Type 2 diabetes.
- Kidney failure.
- Pulmonary embolism, or a blood clot in the lung.
- Myocarditis, an inflamed heart.
While it’s hard to say precisely whether these conditions were caused by COVID, they are most likely linked to it, says Dr. Schamess. A March 2022 study published in The Lancet Diabetes & Endocrinology, for example, found that people who had recovered from COVID-19 had a 40% higher risk of being diagnosed with type 2 diabetes over the next year.
“We don’t know for sure that infection with COVID-19 triggered someone’s diabetes – it may have been that they already had risk factors and the virus pushed them over the edge,” he says.
COVID-19 itself may also worsen conditions you already have, such as asthma, sleep apnea, or fibromyalgia. “We see patients with previously mild asthma who come in constantly coughing and wheezing, for example,” says Dr. Schamess. “They usually respond well once we start aggressive treatment.” That might include a continuous positive airway pressure, or CPAP, setup to help treat sleep apnea, or gabapentin to treat fibromyalgia symptoms.
Is it long COVID or something else?
Long COVID can cause a long list of symptoms, and they can easily mean other ailments. That’s one reason why, if your symptoms last for more than a month, it’s important to see a doctor, Ms. Baloun says. They can run a wide variety of tests to check for other conditions, such as a thyroid disorder or vitamin deficiency, that could be confused with long COVID.
They should also run blood tests such as D-dimer. This helps rule out a pulmonary embolism, which can be a complication of COVID-19 and also causes symptoms that may mimic long COVID, such as breathlessness and anxiety. They will also run tests to look for inflammation, Ms. Baloun says.
“These tests can’t provide definitive answers, but they can help provide clues as to what’s causing symptoms and whether they are related to long COVID,” she says.
What’s just as important, says Dr. Schamess, is a careful medical history. This can help pinpoint exactly when symptoms started, when they worsened, and whether anything else could have triggered them.
“I saw a patient recently who presented with symptoms of brain fog, memory loss, fatigue, headache, and sleep disturbance 5 months after she had COVID-19,” says Dr. Schamess. “After we talked, we realized that her symptoms were due to a fainting spell a couple of months earlier where she whacked her head very hard. She didn’t have long COVID – she had a concussion. But I wouldn’t have picked that up if I had just run a whole battery of tests.”
Ms. Stern agrees. “If you have long COVID, you may come across doctors who dismiss your symptoms, especially if your workups don’t show an obvious problem,” she says. “But you know your body. If it still seems like something is wrong, then you need to continue to push until you find answers.”
A version of this article first appeared on WebMD.com.
Long COVID-19 in children and adolescents: What do we know?
Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate.
Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).
The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
Definitions are changing
In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”
Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.
In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).
These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”
The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.
In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.
The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.
The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).
In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.
The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.
“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”
“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”
The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
Danish parent survey
The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.
Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.
Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.
Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
More information needed
Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.
Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”
Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.
She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”
Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”
There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.
This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.
Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate.
Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).
The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
Definitions are changing
In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”
Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.
In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).
These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”
The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.
In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.
The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.
The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).
In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.
The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.
“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”
“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”
The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
Danish parent survey
The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.
Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.
Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.
Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
More information needed
Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.
Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”
Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.
She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”
Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”
There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.
This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.
Among scientists, the existence of long COVID-19 in children and adolescents has been the subject of debate.
Published by a Mexican multidisciplinary group in Scientific Reports, the first study is a systematic review and meta-analysis. It identified mood symptoms as the most prevalent clinical manifestations of long COVID-19 in children and adolescents. These symptoms included sadness, tension, anger, depression, and anxiety (16.50%); fatigue (9.66%); and sleep disorders (8.42%).
The second study, LongCOVIDKidsDK, was conducted in Denmark. It compared 11,000 children younger than 14 years who had tested positive for COVID-19 with 33,000 children who had no history of COVID-19. The study was published in The Lancet Child and Adolescent Health.
Definitions are changing
In their meta-analysis, the researchers estimated the prevalence and counted signs and symptoms of long COVID-19, as defined by the United Kingdom’s National Institute for Health and Care Excellence. Long COVID-19 was defined as the presence of one or more symptoms more than 4 weeks after SARS-CoV-2 infection. For search terms, the researchers used “COVID-19,” “COVID,” “SARSCOV-2,” “coronavirus,” “long COVID,” “postCOVID,” “PASC,” “long-haulers,” “prolonged,” “post-acute,” “persistent,” “convalescent,” “sequelae,” and “postviral.”
Of the 8,373 citations returned by the search as of Feb. 10, 2022, 21 prospective studies, 2 of them on preprint servers, met the authors’ selection criteria. Those studies included a total of 80,071 children and adolescents younger than 18 years.
In the meta-analysis, the prevalence of long COVID-19 among children and adolescents was reported to be 25.24% (95% confidence interval, 18.17-33.02; I2, 99.61%), regardless of whether the case had been asymptomatic, mild, moderate, severe, or serious. For patients who had been hospitalized, the prevalence was 29.19% (95% CI, 17.83-41.98; I2, 80.84%).
These numbers, while striking, are not the focus of the study, according to first author Sandra Lopez-Leon, MD, PhD, associate professor of pharmacoepidemiology at Rutgers University, New Brunswick, N.J. “It’s important that we don’t focus on that 25%,” she said in an interview. “It’s a disease that we’re learning about, we’re at a time when the definitions are still changing, and, depending on when it is measured, a different number will be given. The message we want to give is that long COVID-19 exists, it’s happening in children and adolescents, and patients need this recognition. And also to show that it can affect the whole body.”
The study showed that the children and adolescents who presented with SARS-CoV-2 infection were at higher risk of subsequent long dyspnea, anosmia/ageusia, or fever, compared with control persons.
In total, in the studies that were included, more than 40 long-term clinical manifestations associated with COVID-19 in the pediatric population were identified.
The most common symptoms among children aged 0-3 years were mood swings, skin rashes, and stomachaches. In 4- to 11-year-olds, the most common symptoms were mood swings, trouble remembering or concentrating, and skin rashes. In 12- to 14-year-olds, they were fatigue, mood swings, and trouble remembering or concentrating. These data are based on parent responses.
The list of signs and symptoms also includes headache, respiratory symptoms, cognitive symptoms (such as decreased concentration, learning difficulties, confusion, and memory loss), loss of appetite, and smell disorder (hyposmia, anosmia, hyperosmia, parosmia, and phantom smell).
In the studies, the prevalence of the following symptoms was less than 5%: hyperhidrosis, chest pain, dizziness, cough, myalgia/arthralgia, changes in body weight, taste disorder, otalgia (tinnitus, ear pain, vertigo), ophthalmologic symptoms (conjunctivitis, dry eye, blurred vision, photophobia, pain), dermatologic symptoms (dry skin, itchy skin, rashes, hives, hair loss), urinary symptoms, abdominal pain, throat pain, chest tightness, variations in heart rate, palpitations, constipation, dysphonia, fever, diarrhea, vomiting/nausea, menstrual changes, neurological abnormalities, speech disorders, and dysphagia.
The authors made it clear that the frequency and severity of these symptoms can fluctuate from one patient to another.
“The meta-analysis is important because it brings together 21 studies selected from more than 8,000 articles – and in them, a large number of children – to study the most common manifestations of long COVID-19,” Gabriela Ensinck, MD, head of the infectious diseases department at the Víctor J. Vilela Children’s Hospital in Rosario, Argentina, told this news organization. Dr. Ensinck did not participate in the study. “The important thing here is that long COVID-19 exists in pediatrics. And that it is a prolongation of signs or symptoms over time, a time for which there is no single definition.”
“It’s a snapshot of all the symptoms that can remain after COVID-19,” Dr. Lopez-Leon explained. “The meta-analysis seeks to see if there’s an association between having had COVID-19 and having the symptoms, but at no time does it speak of causality.”
The prevalence of symptoms largely depends on the time since the onset of acute COVID-19. Most symptoms improve over time. In the studies that were included in the meta-analysis, the follow-up time varied between 1 and 13 months. It is important to understand what symptoms are associated with each period after the onset of infection, the authors said.
Danish parent survey
The Danish study LongCOVIDKidsDK followed the World Health Organization criteria for long COVID-19 and included children and adolescents aged 0-14 years who received a diagnosis of COVID-19 and who experienced symptoms that lasted at least 2 months.
Between July 20, 2021, and Sept. 15, 2021, a questionnaire was sent to 38,152 case patients and 147,212 control persons. Of this group, 10,997 (28.8%) case patients and 33,016 (22.4%) control persons answered the survey.
Children who had been diagnosed with SARS-CoV-2 infection were more likely to experience long-lasting symptoms than children who had never been diagnosed. Approximately one-third of children with a positive SARS-CoV-2 test experienced symptoms that were not present before infection. Children who experienced long-lasting symptoms included 40% of children diagnosed with COVID-19 and 27% of control persons aged 0-3 years, 38% of case patients and 34% of control persons aged 4-11 years, and 46% of case patients and 41% of control persons aged 12-14 years.
Interestingly, those diagnosed with COVID-19 reported fewer psychological and social problems than those in the control group. Among the oldest (aged 12-14 years), quality of life scores were higher and anxiety scores were lower for those who had tested positive for SARS-CoV-2.
More information needed
Given the diversity of symptoms in the meta-analysis and the LongCOVIDKidsDK study, a multidisciplinary approach is imperative. Dr. Lopez-Leon suggests that there is a need to raise awareness among parents, clinicians, researchers, and the health system about the conditions that can occur after COVID-19. Clinicians must better understand the sequelae to provide targeted care and treatment. The authors of the Danish study recommend establishing clinics for long COVID-19 with multispecialty care.
Maren J. Heilskov Rytter, PhD, associate professor of clinical medicine at the University of Copenhagen, wrote an editorial in The Lancet Child and Adolescent Health about the Danish study. Until it is clarified whether SARS-CoV-2 does indeed cause persistent symptoms, she wrote, “it seems excessive and premature to establish specific multidisciplinary clinics for children with long COVID-19.”
Dr. Rytter highlighted the difficulty of interpreting LongCOVIDKidsDK data, owing to recall bias, the failure to exclude other causes of symptoms in the cases analyzed, and the number of symptoms in the control persons. In addition, the data analyzed in Denmark are of limited clinical relevance, she said, given a greater presence of mild symptoms and, paradoxically, a higher quality of life.
She concluded, “In the majority of children with nonspecific symptoms after COVID-19, the symptoms presented are more likely to have been caused by something other than COVID-19, and if they are related to COVID-19, they are likely to go away over time.”
Dr. Ensinck, who is coauthor of the Argentine Ministry of Health’s guide for long COVID-19 monitoring for children and adolescents and who represented the Infectious Diseases Committee of the Argentine Society of Pediatrics, highlighted another aspect of the problem. “What should be taken into account in these data is to see how much the confinement contributed. Children are the ones who suffered the most in the period in which schools were closed; they could not meet their peers, they had sick relatives, they felt fear. … all this must be taken into account.”
There is as yet no agreement on how to define and diagnose long COVID-19 in adults, a population that has been studied more closely. Part of the problem is that long COVID-19 has been linked to more than 200 symptoms, which can range in severity from inconvenient to debilitating, can last for months or years, and can recur, sometimes months after apparent recovery. Thus, there are still disparate answers to basic questions about the syndrome’s frequency and its effects on vaccination, reinfection, and the latest variant of SARS-CoV-2.
This article has been translated from the Medscape Spanish edition. A version appeared on Medscape.com.
FROM SCIENTIFIC REPORTS AND THE LANCET CHILD AND ADOLESCENT HEALTH
Many sources of PTSD are cause for concern
A few weeks ago, right after 19 children and two adults were killed by a gunman in Uvalde, Texas, Americans were really on edge. Many people I know became hypervigilant while going about activities previously thought of as routine, such as waiting for a subway or going to a grocery store.
On top of that, we are still facing the ongoing COVID-19 pandemic. Despite vaccines and therapeutics, the United States is still losing more than 300 people each day to the virus. Many people who have tested positive have continued to experience debilitating long-haul symptoms many months after testing negative, and I believe not knowing what your future life will bring from this terrible illness could lead some to posttraumatic stress disorder.
In addition to constant updates about COVID, we are getting almost daily reports about monkeypox. In New York state, medical professionals and institutions receive regular, almost weekly, information about the spread of influenza. But where are the reports and treatment approaches for PTSD, which would not only increase awareness but also lead to more care?
Some might believe that I am obsessed with PTSD, since I’ve written a great deal on the subject, particularly “underdiagnosed” PTSD. The key question I have is:
We know the signs and symptoms of PTSD. They include flashbacks, intrusive recollections, physical distress related to stimuli related to the trauma, insomnia, social isolation, avoidance of certain situations, negative thinking, and hyperarousal – coupled with anxiety and depression. PTSD can be a great masquerader. It can be triggered by many events, large and small, and all too often will masquerade as general anxiety or existential despair and depression. Too often, PTSD is undiagnosed or unrecognized completely. PTSD is also a costly disease that is an enormous economic burden on the U.S. economy.
As clinicians, we must be aware of the more subtle events that may trigger PTSD. We must think beyond ICD codes and DSM criteria and realize that each individual processes an event or a series of events differently. For example, seriously ill people in ICUs or undergoing critical care have been known to experience PTSD well beyond their physical recovery (J Crit Care. 2017 Dec. doi: 10.1016/j.jcrc.2017.06.014). Years after the Sept. 11, 2001, World Trade Center disaster, many are still suffering from PTSD symptoms (Biol Psychiatry. 2020 May 1. doi: 10.1016/j.biopsych.2020.02.817).
Again, in some cases, not knowing what the future may bring regarding life itself can lead to PTSD. I have treated patients who have lost jobs and experienced devastating social and financial losses, which were perceived as a separation from “life as they know it.” These can be precursors to PTSD for some who are sensitive to the disorder.
Intergenerational trauma is also a real phenomenon to which we must be attuned. I have treated two adult children of Holocaust survivors, both born in America well after World War II, who developed PTSD after hearing family recollections over and over about the brutality suffered by relatives, combined with watching films about people sent to concentration camps. Both of those patients self-diagnosed their symptoms as depression. Research shows that Holocaust traumatization can affect three generations (J Anxiety Disord. 2021 Jun. doi: 10.1016/j.janxdis.2021.102401).
In light of the high incidence of traumatic events affecting millions directly, more codified treatment approaches are needed that can be used both for individuals and for those in group settings.
To date, the best treatment rests with cognitive-behavioral therapy (CBT) and guided imagery coupled with relaxation techniques and the various types of in vivo exposure therapy, which I prefer to in vitro or flooding care. In terms of medication management, the U.S. Food and Drug Administration has approved only two antidepressant medications for PTSD, sertraline (Zoloft) and paroxetine (Paxil), although other selective serotonin reuptake inhibitors have been used off- label, and prazosin, a hypertensive medication, has been used off-label for PTSD-related insomnia and nightmares (Prim Care Companion CNS Disord. 2012 Mar 22. doi: 10.4088/PCC.11r01222). Thus, the limited number of choices for medication management means more research is needed so that more medications are developed that are more precisely directed at PTSD treatment.
Implications for society at large
In a recent article published in the Journal of Clinical Psychiatry (2022 Apr 25. doi: 10.4088/JCP.21m14116), authors Lori L. Davis and colleagues point out that the economic burden of PTSD goes beyond health care costs and rivals the costs of other mental illnesses, including depression and anxiety. In the process, Dr. Davis and colleagues note, unemployment caused by job loss, disability, homelessness, substance use, disordered care, as well as premature mortality, all contribute to this severe burden, going beyond PTSD itself.
This study shows that the annual economic burden of PTSD is $232 billion. Most of that burden is attributed to the civilian population, which they suggest to be $189.5 billion, or 82%.
After reading that article, it became clear to me that my “obsession” with PTSD is not really an obsession at all. Rather, it is a true concern that, against the backdrop of long COVID, gun violence, political and economic turmoil, and other factors, it is important that clinicians understand how to recognize and treat PTSD. The stakes have never been higher.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
A few weeks ago, right after 19 children and two adults were killed by a gunman in Uvalde, Texas, Americans were really on edge. Many people I know became hypervigilant while going about activities previously thought of as routine, such as waiting for a subway or going to a grocery store.
On top of that, we are still facing the ongoing COVID-19 pandemic. Despite vaccines and therapeutics, the United States is still losing more than 300 people each day to the virus. Many people who have tested positive have continued to experience debilitating long-haul symptoms many months after testing negative, and I believe not knowing what your future life will bring from this terrible illness could lead some to posttraumatic stress disorder.
In addition to constant updates about COVID, we are getting almost daily reports about monkeypox. In New York state, medical professionals and institutions receive regular, almost weekly, information about the spread of influenza. But where are the reports and treatment approaches for PTSD, which would not only increase awareness but also lead to more care?
Some might believe that I am obsessed with PTSD, since I’ve written a great deal on the subject, particularly “underdiagnosed” PTSD. The key question I have is:
We know the signs and symptoms of PTSD. They include flashbacks, intrusive recollections, physical distress related to stimuli related to the trauma, insomnia, social isolation, avoidance of certain situations, negative thinking, and hyperarousal – coupled with anxiety and depression. PTSD can be a great masquerader. It can be triggered by many events, large and small, and all too often will masquerade as general anxiety or existential despair and depression. Too often, PTSD is undiagnosed or unrecognized completely. PTSD is also a costly disease that is an enormous economic burden on the U.S. economy.
As clinicians, we must be aware of the more subtle events that may trigger PTSD. We must think beyond ICD codes and DSM criteria and realize that each individual processes an event or a series of events differently. For example, seriously ill people in ICUs or undergoing critical care have been known to experience PTSD well beyond their physical recovery (J Crit Care. 2017 Dec. doi: 10.1016/j.jcrc.2017.06.014). Years after the Sept. 11, 2001, World Trade Center disaster, many are still suffering from PTSD symptoms (Biol Psychiatry. 2020 May 1. doi: 10.1016/j.biopsych.2020.02.817).
Again, in some cases, not knowing what the future may bring regarding life itself can lead to PTSD. I have treated patients who have lost jobs and experienced devastating social and financial losses, which were perceived as a separation from “life as they know it.” These can be precursors to PTSD for some who are sensitive to the disorder.
Intergenerational trauma is also a real phenomenon to which we must be attuned. I have treated two adult children of Holocaust survivors, both born in America well after World War II, who developed PTSD after hearing family recollections over and over about the brutality suffered by relatives, combined with watching films about people sent to concentration camps. Both of those patients self-diagnosed their symptoms as depression. Research shows that Holocaust traumatization can affect three generations (J Anxiety Disord. 2021 Jun. doi: 10.1016/j.janxdis.2021.102401).
In light of the high incidence of traumatic events affecting millions directly, more codified treatment approaches are needed that can be used both for individuals and for those in group settings.
To date, the best treatment rests with cognitive-behavioral therapy (CBT) and guided imagery coupled with relaxation techniques and the various types of in vivo exposure therapy, which I prefer to in vitro or flooding care. In terms of medication management, the U.S. Food and Drug Administration has approved only two antidepressant medications for PTSD, sertraline (Zoloft) and paroxetine (Paxil), although other selective serotonin reuptake inhibitors have been used off- label, and prazosin, a hypertensive medication, has been used off-label for PTSD-related insomnia and nightmares (Prim Care Companion CNS Disord. 2012 Mar 22. doi: 10.4088/PCC.11r01222). Thus, the limited number of choices for medication management means more research is needed so that more medications are developed that are more precisely directed at PTSD treatment.
Implications for society at large
In a recent article published in the Journal of Clinical Psychiatry (2022 Apr 25. doi: 10.4088/JCP.21m14116), authors Lori L. Davis and colleagues point out that the economic burden of PTSD goes beyond health care costs and rivals the costs of other mental illnesses, including depression and anxiety. In the process, Dr. Davis and colleagues note, unemployment caused by job loss, disability, homelessness, substance use, disordered care, as well as premature mortality, all contribute to this severe burden, going beyond PTSD itself.
This study shows that the annual economic burden of PTSD is $232 billion. Most of that burden is attributed to the civilian population, which they suggest to be $189.5 billion, or 82%.
After reading that article, it became clear to me that my “obsession” with PTSD is not really an obsession at all. Rather, it is a true concern that, against the backdrop of long COVID, gun violence, political and economic turmoil, and other factors, it is important that clinicians understand how to recognize and treat PTSD. The stakes have never been higher.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
A few weeks ago, right after 19 children and two adults were killed by a gunman in Uvalde, Texas, Americans were really on edge. Many people I know became hypervigilant while going about activities previously thought of as routine, such as waiting for a subway or going to a grocery store.
On top of that, we are still facing the ongoing COVID-19 pandemic. Despite vaccines and therapeutics, the United States is still losing more than 300 people each day to the virus. Many people who have tested positive have continued to experience debilitating long-haul symptoms many months after testing negative, and I believe not knowing what your future life will bring from this terrible illness could lead some to posttraumatic stress disorder.
In addition to constant updates about COVID, we are getting almost daily reports about monkeypox. In New York state, medical professionals and institutions receive regular, almost weekly, information about the spread of influenza. But where are the reports and treatment approaches for PTSD, which would not only increase awareness but also lead to more care?
Some might believe that I am obsessed with PTSD, since I’ve written a great deal on the subject, particularly “underdiagnosed” PTSD. The key question I have is:
We know the signs and symptoms of PTSD. They include flashbacks, intrusive recollections, physical distress related to stimuli related to the trauma, insomnia, social isolation, avoidance of certain situations, negative thinking, and hyperarousal – coupled with anxiety and depression. PTSD can be a great masquerader. It can be triggered by many events, large and small, and all too often will masquerade as general anxiety or existential despair and depression. Too often, PTSD is undiagnosed or unrecognized completely. PTSD is also a costly disease that is an enormous economic burden on the U.S. economy.
As clinicians, we must be aware of the more subtle events that may trigger PTSD. We must think beyond ICD codes and DSM criteria and realize that each individual processes an event or a series of events differently. For example, seriously ill people in ICUs or undergoing critical care have been known to experience PTSD well beyond their physical recovery (J Crit Care. 2017 Dec. doi: 10.1016/j.jcrc.2017.06.014). Years after the Sept. 11, 2001, World Trade Center disaster, many are still suffering from PTSD symptoms (Biol Psychiatry. 2020 May 1. doi: 10.1016/j.biopsych.2020.02.817).
Again, in some cases, not knowing what the future may bring regarding life itself can lead to PTSD. I have treated patients who have lost jobs and experienced devastating social and financial losses, which were perceived as a separation from “life as they know it.” These can be precursors to PTSD for some who are sensitive to the disorder.
Intergenerational trauma is also a real phenomenon to which we must be attuned. I have treated two adult children of Holocaust survivors, both born in America well after World War II, who developed PTSD after hearing family recollections over and over about the brutality suffered by relatives, combined with watching films about people sent to concentration camps. Both of those patients self-diagnosed their symptoms as depression. Research shows that Holocaust traumatization can affect three generations (J Anxiety Disord. 2021 Jun. doi: 10.1016/j.janxdis.2021.102401).
In light of the high incidence of traumatic events affecting millions directly, more codified treatment approaches are needed that can be used both for individuals and for those in group settings.
To date, the best treatment rests with cognitive-behavioral therapy (CBT) and guided imagery coupled with relaxation techniques and the various types of in vivo exposure therapy, which I prefer to in vitro or flooding care. In terms of medication management, the U.S. Food and Drug Administration has approved only two antidepressant medications for PTSD, sertraline (Zoloft) and paroxetine (Paxil), although other selective serotonin reuptake inhibitors have been used off- label, and prazosin, a hypertensive medication, has been used off-label for PTSD-related insomnia and nightmares (Prim Care Companion CNS Disord. 2012 Mar 22. doi: 10.4088/PCC.11r01222). Thus, the limited number of choices for medication management means more research is needed so that more medications are developed that are more precisely directed at PTSD treatment.
Implications for society at large
In a recent article published in the Journal of Clinical Psychiatry (2022 Apr 25. doi: 10.4088/JCP.21m14116), authors Lori L. Davis and colleagues point out that the economic burden of PTSD goes beyond health care costs and rivals the costs of other mental illnesses, including depression and anxiety. In the process, Dr. Davis and colleagues note, unemployment caused by job loss, disability, homelessness, substance use, disordered care, as well as premature mortality, all contribute to this severe burden, going beyond PTSD itself.
This study shows that the annual economic burden of PTSD is $232 billion. Most of that burden is attributed to the civilian population, which they suggest to be $189.5 billion, or 82%.
After reading that article, it became clear to me that my “obsession” with PTSD is not really an obsession at all. Rather, it is a true concern that, against the backdrop of long COVID, gun violence, political and economic turmoil, and other factors, it is important that clinicians understand how to recognize and treat PTSD. The stakes have never been higher.
Dr. London is a practicing psychiatrist and has been a newspaper columnist for 35 years, specializing in and writing about short-term therapy, including cognitive-behavioral therapy and guided imagery. He is author of “Find Freedom Fast” (New York: Kettlehole Publishing, 2019). He has no conflicts of interest.
IBD study hints at cause of postacute COVID
A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.
Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.
Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.
The study was published online in Gastroenterology.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.
Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.
One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.
To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.
The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.
The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.
In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.
There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.
The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.
The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.
The researchers have no relevant financial disclosures.
Understanding the cause and risk factors for the postacute COVID-19 condition is an urgent research priority. The study by Zollner et al. found new clues about the cause of the post–COVID-19 condition in intestinal tissues of patients with IBD. The first important finding was that most adult patients with IBD have persistent viral antigen in their intestine months after even mild acute COVID-19. Importantly, researchers could not recover replicating virus from these tissues, indicating there was unlikely persistent active infection or viral transmissibility. The second major finding was that the presence of persistent viral antigen in intestinal tissue was strongly associated with postacute COVID-19 symptoms. This suggests that persistence of SARS‑CoV‑2 antigen after acute infection could perpetuate an ongoing inflammatory response that causes the postacute COVID-19 condition.
Zollner et al. used the intestine as a window onto how this virus may lead to long-lasting symptoms in IBD patients. However, it does not change our understanding that corticosteroids, poorly controlled IBD, and comorbidities, and not biologic or immunomodulator therapy, increase the risk of severe illness and mortality related to acute COVID-19 in IBD patients.
Michael J. Rosen, MD, MSCI, is Endowed Professor for Pediatric IBD & Celiac Disease and director for the Center for Pediatric IBD & Celiac Disease at Stanford (Calif.) University. Dr. Rosen served on an advisory board for Pfizer.
Understanding the cause and risk factors for the postacute COVID-19 condition is an urgent research priority. The study by Zollner et al. found new clues about the cause of the post–COVID-19 condition in intestinal tissues of patients with IBD. The first important finding was that most adult patients with IBD have persistent viral antigen in their intestine months after even mild acute COVID-19. Importantly, researchers could not recover replicating virus from these tissues, indicating there was unlikely persistent active infection or viral transmissibility. The second major finding was that the presence of persistent viral antigen in intestinal tissue was strongly associated with postacute COVID-19 symptoms. This suggests that persistence of SARS‑CoV‑2 antigen after acute infection could perpetuate an ongoing inflammatory response that causes the postacute COVID-19 condition.
Zollner et al. used the intestine as a window onto how this virus may lead to long-lasting symptoms in IBD patients. However, it does not change our understanding that corticosteroids, poorly controlled IBD, and comorbidities, and not biologic or immunomodulator therapy, increase the risk of severe illness and mortality related to acute COVID-19 in IBD patients.
Michael J. Rosen, MD, MSCI, is Endowed Professor for Pediatric IBD & Celiac Disease and director for the Center for Pediatric IBD & Celiac Disease at Stanford (Calif.) University. Dr. Rosen served on an advisory board for Pfizer.
Understanding the cause and risk factors for the postacute COVID-19 condition is an urgent research priority. The study by Zollner et al. found new clues about the cause of the post–COVID-19 condition in intestinal tissues of patients with IBD. The first important finding was that most adult patients with IBD have persistent viral antigen in their intestine months after even mild acute COVID-19. Importantly, researchers could not recover replicating virus from these tissues, indicating there was unlikely persistent active infection or viral transmissibility. The second major finding was that the presence of persistent viral antigen in intestinal tissue was strongly associated with postacute COVID-19 symptoms. This suggests that persistence of SARS‑CoV‑2 antigen after acute infection could perpetuate an ongoing inflammatory response that causes the postacute COVID-19 condition.
Zollner et al. used the intestine as a window onto how this virus may lead to long-lasting symptoms in IBD patients. However, it does not change our understanding that corticosteroids, poorly controlled IBD, and comorbidities, and not biologic or immunomodulator therapy, increase the risk of severe illness and mortality related to acute COVID-19 in IBD patients.
Michael J. Rosen, MD, MSCI, is Endowed Professor for Pediatric IBD & Celiac Disease and director for the Center for Pediatric IBD & Celiac Disease at Stanford (Calif.) University. Dr. Rosen served on an advisory board for Pfizer.
A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.
Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.
Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.
The study was published online in Gastroenterology.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.
Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.
One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.
To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.
The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.
The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.
In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.
There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.
The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.
The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.
The researchers have no relevant financial disclosures.
A new study among patients with inflammatory bowel disease (IBD) suggests that viral antigen persistence in the gut may contribute to post-acute COVID-19 syndrome.
Postacute COVID-19 syndrome is now understood to be a multiorgan condition with symptoms that may include fatigue, cognitive dysfunction, and pain. Poor baseline health and severe acute infection are risk factors for the condition, but nonhospitalized illness can also lead to persistent symptoms.
Researchers found that nearly two-thirds of IBD patients had persistence of the antigen in infected tissues up to 8 months after a mild (nonhospitalized) acute COVID-19 infection. The study is the first to tie gut antigen persistence to post-acute COVID symptoms, and the results imply that the antigen may lead to immune perturbation and ongoing symptoms.
The study was published online in Gastroenterology.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane-bound angiotensin-converting enzyme 2 to gain entry into cells, which is expressed in the brush border enterocytes, as well as elsewhere in the body.
Previous research using intestinal epithelial organoids confirmed that SARS-CoV-2 is capable of infecting the human epithelium and that the virus can be detected in anal swabs long after it is cleared from nasal passages.
One potential explanation is viral immune perturbation or inflammatory tissue injury. Supporting evidence includes neural accumulation of memory T cells in patients with neuropsychiatric symptoms such as malaise and depression, and similar changes are seen with age-related immune senescence and tissue injury. Hyperactivated B and T cells, as well as other innate immune cells, have also been linked to postacute COVID-19, as has heightened expression of proinflammatory cytokines.
To explore the potential role of persistent viral antigens, the researchers gathered biopsies during upper- and lower-gastrointestinal endoscopy in 46 patients with IBD whose prior COVID-19 infection (mean, 7.3 months previous) had been confirmed by polymerase chain reaction and who were seen at the IBD outpatient unit of the investigators’ institution. In all, 43.5% of patients were female, and the average age was 44.67 years. Overall, 67.4% had been diagnosed with Crohn’s disease, 28.3% with ulcerative colitis, and 4.3% had unclassified IBD; 23.9% had a history of exposure to anti–tumor necrosis factor therapy. Among patients in the study, 32 of the patients tested positive for mucosal SARS-CoV-2 RNA, and there was no association between the presence of viral RNA and IBD type.
The researchers found that 52%-70% of patients had antigen persistence in any gut segment, as measured by nucleocapsid immunofluorescence or expression of one of four viral transcripts. They detected persistence of the nucleocapsid in epithelial cells and CD8+ T cells. Viral antigens persisted in patients with and without exposure to immunosuppressive therapy, and there was no association with antigen persistence and severity of acute COVID-19 infection or the presence of inflammation at the time of the endoscopy.
The researchers believed that the persistent viral antigen reflects incomplete clearance from the original infection rather than a latent or persistent infection because they could not replicate the virus in biopsy samples. Most biopsies within a patient produced some, but not all, of the viral transcripts tested. The authors suggest that immunosuppressive therapy may lead to incomplete viral clearance. Some patients lacked humoral nucleocapsid IgG antibodies, especially among those with gut antigen persistence.
In fact, only patients with gut viral RNA persistence had symptoms of postacute COVID. “This observation strongly argues for a role of viral antigen persistence in postacute COVID-19 and it appears plausible that SARS-CoV-2 antigen persistence, possibly in infected tissues beyond the gut, could impact host immune responses underlying the postacute COVID-19 syndrome,” the researchers wrote.
There is precedent for such a phenomenon in influenza. Mouse models have shown that ineffective clearance can influence adaptive immune responses and memory T-cell formation in lymph nodes of the lung. Another report found that COVID-19 pneumonia survivors have persistent changes to pulmonary CD8+ T cells.
The study is limited by its small sample size and a lack of a replication cohort. The study was also conducted in IBD patients because the researchers believed they were at higher risk of COVID-19 infection, although the researchers note that viral antigen persistence has been observed 2 months after recovery from COVID-19 in patients without IBD or exposure to immunosuppressants.
The researchers call for studies in patients without IBD to determine whether viral antigen persistence is a key mechanism in postacute COVID-19.
The researchers have no relevant financial disclosures.
FROM GASTROENTEROLOGY
ACC/AHA issue clinical lexicon for complications of COVID-19
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
The American College of Cardiology and the American Heart Association have jointly issued a comprehensive set of data standards to help clarify definitions of the cardiovascular (CV) and non-CV complications of COVID-19.
It’s the work of the ACC/AHA Task Force on Clinical Data Standards and has been endorsed by the Heart Failure Society of America and Society for Cardiac Angiography and Interventions.
There is increased importance to understanding the acute and long-term impact of COVID-19 on CV health, the writing group notes. Until now, however, there has not been “clarity or consensus” on definitions of CV conditions related to COVID-19, with different diagnostic terminologies being used for overlapping conditions, such as “myocardial injury,” “myocarditis,” “type Il myocardial infarction,” “stress cardiomyopathy,” and “inflammatory cardiomyopathy,” they point out.
“We, as a research community, did some things right and some things wrong surrounding the COVID pandemic,” Sandeep Das, MD, MPH, vice chair of the writing group, noted in an interview with this news organization.
“The things that we really did right is that everybody responded with enthusiasm, kind of all hands on deck with a massive crisis response, and that was fantastic,” Dr. Das said.
“However, because of the need to hurry, we didn’t structure and organize in the way that we typically would for something that was sort of a slow burn kind of problem rather than an emergency. One of the consequences of that was fragmentation of how things are collected, reported, et cetera, and that leads to confusion,” he added.
The report was published simultaneously June 23 in the Journal of the American College of Cardiology and Circulation: Cardiovascular Quality and Outcomes.
A necessary but not glamorous project
The new data standards for COVID-19 will help standardize definitions and set the framework to capture and better understand how COVID-19 affects CV health.
“It wasn’t exactly a glamorous-type project but, at the same time, it’s super necessary to kind of get everybody on the same page and working together,” Dr. Das said.
Broad agreement on common vocabulary and definitions will help with efforts to pool or compare data from electronic health records, clinical registries, administrative datasets, and other databases, and determine whether these data apply to clinical practice and research endeavors, the writing group says.
They considered data elements relevant to the full range of care provided to COVID-19 patients in all care settings. Among the key items included in the document are:
- Case definitions for confirmed, probable, and suspected acute COVID-19, as well as postacute sequelae of COVID-19.
- Definitions for acute CV complications related to COVID-19, including acute myocardial injury, heart failure, shock, arrhythmia, thromboembolic complications, and .
- Data elements related to COVID-19 vaccination status, comorbidities, and preexisting CV conditions.
- Definitions for postacute CV sequelae of SARS-CoV-2 infection and long-term CV complications of COVID-19.
- Data elements for CV mortality during acute COVID-19.
- Data elements for non-CV complications to help document severity of illness and other competing diagnoses and complications that might affect CV outcomes.
- A list of symptoms and signs related to COVID-19 and CV complications.
- Data elements for diagnostic and therapeutic strategies for COVID-19 and CV conditions.
- A discussion of advanced therapies, including , extracorporeal membrane oxygenation, and end-of-life management strategies.
These data standards will be useful for researchers, registry developers, and clinicians, and they are proposed as a framework for ICD-10 code development of COVID-19–related CV conditions, the writing group says.
The standards are also of “great importance” to patients, clinicians, investigators, scientists, administrators, public health officials, policymakers, and payers, the group says.
Dr. Das said that, although there is no formal plan in place to update the document, he could see sections that might be refined.
“For example, there’s a nice long list of all the various variants, and unfortunately, I suspect that that is going to change and evolve over time,” Dr. Das told this news organization.
“We tried very hard not to include things like specifying specific treatments so we didn’t get proscriptive. We wanted to make it descriptive, so hopefully it will stand the test of time pretty well,” he added.
This research had no commercial funding. The writing group has no relevant disclosures.
A version of this article first appeared on Medscape.com.
Noninvasive brain stimulation promising for COVID-related smell loss
Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.
Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.
“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.
tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.
The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
First study of its kind
Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.
Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.
“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.
Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.
The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.
Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.
In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.
A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.
The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.
The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.
The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.
The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.
Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.
This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.
Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
Encouraging results offer new hope
Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.
“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”
“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.
“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.
“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.
A version of this article first appeared on Medscape.com.
Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.
Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.
“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.
tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.
The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
First study of its kind
Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.
Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.
“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.
Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.
The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.
Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.
In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.
A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.
The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.
The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.
The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.
The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.
Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.
This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.
Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
Encouraging results offer new hope
Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.
“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”
“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.
“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.
“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.
A version of this article first appeared on Medscape.com.
Noninvasive brain stimulation may help restore a sense of smell in patients with chronic anosmia or hyposmia related to COVID-19, early research suggests.
Results of a small, double-blind, sham-controlled study showed anodal transcranial direct current stimulation (A-tDCS) combined with olfactory training (OT) provided notable and durable improvement in seven patients with persistent COVID-19–related hyposmia or anosmia.
“We are proud and very excited about these results. Although seven patients is a small sample, it is still notable,” lead investigator Fabio Bandini, MD, head of the department of neurology, ASL 3 Genovese, Genoa, Italy, said in an interview.
tDCS is cheap, safe, accessible, and very easy to administer. It has been used in rehabilitative treatment for 15 years, but this is the first time it has been used for this kind of problem, Dr. Bandini added.
The study was published online in the Journal of Neurology, Neurosurgery, and Psychiatry.
First study of its kind
Approximately 1% of patients with COVID will suffer from long-term smell loss, and given the widespread global impact of COVID, this represents a substantial number who have experienced or will potentially experience chronic smell loss because of the disease.
Loss of smell associated with COVID may last anywhere from 15 to 180 days after a SAR-CoV-2 infection, the researchers noted. Research suggests there is central nervous system involvement in COVID anosmia, mostly in the orbitofrontal cortex – the neural substrate for conscious olfactory perception.
“Smell loss has important consequences in everyday life for food, for hazards, for socialization. Usually, you recover from smell loss after 2 or 3 months, but after 6 months, that is considered permanent,” said Dr. Bandini.
Some research has pointed to the activation of the orbital frontal cortex for control of olfactory perception, so Dr. Bandini and colleagues wanted to explore whether stimulating this area could improve smell disturbances in post-COVID patients.
The study included seven consecutive patients with hyposmia or anosmia from COVID-19 lasting at least 6 months and who had a score of less than 12 on the Sniffin’ Sticks identification subtest. Exclusion criteria included severe mood disorder, rhinologic diseases, epilepsy, and sensitive scalp. No medications for alleviating olfactory symptoms were permitted.
Patients’ smell performances were assessed immediately prior to stimulation (t0) and rated on a scale of 0-10, with a score of 0 indicating a complete loss of smell and a score of 10 indicating a full sense of smell as the subjective measure. Sniffin’ Sticks, a validated test that assesses smell threshold, discrimination, and validation, was used as an objective measure.
In the 20-minute OT session, patients had to sniff 10 odors (rose, eucalyptus, lemon, star anise, rosemary, strawberry, coconut, vanilla, pine tree, and bergamot) in a random order for 10 seconds each then were asked to identify the smell and rate its intensity. The training was applied once in each session.
A-tDCS or sham-transcranial direct current stimulation (S-tDCS) was administered at the same time. In the active stimulation the anode was placed over the left prefrontal cortex because the orbitofrontal cortex is not directly accessible by A-tDCS.
The patients participated in olfactory training with S-tDCS for the first 2 weeks. In the second 2 weeks of the study, they received OT with A-tDCS.
The order of sham and A-tDCS stimulation was not counterbalanced to avoid potential carryover effects if A-tDCS had been applied first. The patients and assessors collecting the data were blinded.
The smell assessment was repeated immediately after S-tDCS (t1), A-tDCS (t2) and 3 months from the end of stimulation (t3), using the same odors and the same order of the first assessment.
The Wilcoxon test was used to compare each assessment (t1, t2, and t3) with baseline, indicating a two-sided alpha less than 0.05, which was considered statistically significant.
Both the subjective and objective measures showed a statistically significant improvement at t2 and t3, with average measurements doubled or even tripled, compared with t0 and t1. In addition, all patients demonstrated notable improvement in smell performance.
This study, said Dr. Bandini, is the first to use A-tDCS to treat patients with persistent smell loss due to COVID. Not only did the results show significant improvement in all study participants, compared with baseline but the beneficial effect lasted up to 3 months after treatment, demonstrating a durable effect.
Dr. Bandini noted that the study’s small sample size is a major limitation of the research so he hopes to enlarge it in future research testing A-tDCS for COVID-related smell loss and work toward providing this therapy on an outpatient basis.
Encouraging results offer new hope
Commenting on the research, Cheng-Ying Ho, MD, associate professor of pathology at the Johns Hopkins University, Baltimore, described the study as “interesting and encouraging.
“Even though there is a small percentage of patients that suffer persistent smell loss from COVID, it’s still a large number of people who have smell dysfunction and are unable to recover.”
“So far, there is no treatment for COVID-related or viral infection–related smell loss. The only thing that can be done is olfactory training, but the effect is very limited. There is no drug or other type of therapy for smell loss so far,” said Dr. Ho, whose areas of expertise include neuromuscular pathology, pediatric neuropathology, and neuropathology of infectious diseases.
“Even though it’s a small study with only seven patients, the results are very encouraging. After 2 weeks of stimulation, almost all had smell recovery that lasted several months. The weakness of the study is that they didn’t have a control group. The next step would be to expand the study to include more participants and have an adequate control group that received the sham stimuli to see if their results still stand when they have more participants.
“This very encouraging and relatively noninvasive treatment modality can give patients with smell loss some hope that this therapy can help them recover their sense of smell to some degree. The study seems to suggest that either the tDCS can stimulate nerve regrowth or that it actually can correct the rewiring of the brain,” added Dr. Ho.
The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors. No competing interests were declared.
A version of this article first appeared on Medscape.com.
FROM THE JOURNAL OF NEUROLOGY, NEUROSURGERY, AND PSYCHIATRY