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A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

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


A new study suggests that going beyond current guidance on moderate and vigorous physical activity levels may add years to one’s life.

Americans are advised to do a minimum of 150-300 minutes a week of moderate exercise or 75-150 minutes a week of vigorous exercise, or an equivalent combination of both, according to U.S. Department of Health and Human Services Physical Activity Guidelines.

Results from more than 100,000 U.S. adults followed for 30 years showed that individuals who performed double the currently recommended range of either moderate or vigorous physical activity weekly had the lowest long-term risk of mortality.

Adults who reported completing four times the minimum recommended activity levels saw no clear incremental mortality benefit but also no harm, according to the study, published in the journal Circulation.

“I think we’re worried more about the lower end and people that are not even doing the minimum, but this should be reassuring to people who like to do a lot of exercise,” senior author Edward Giovannucci, MD, ScD, with the Harvard T.H. Chan School of Public Health, Boston, told this news organization.

Some studies have suggested that long-term, high-intensity exercise (e.g., marathons, triathlons, and long-distance cycling) may be associated with increased risks of atrial fibrillation, coronary artery calcification, and sudden cardiac death.

A recent analysis from the Copenhagen City Heart Study showed a U-shaped association between long-term all-cause mortality and 0 to 2.5 hours and more than 10 hours of weekly, leisure-time sports activities.

Most studies suggesting harm, however, have used only one measurement of physical activity capturing a mix of people who chronically exercise at high levels and those who do it sporadically, which possibly can be harmful, Dr. Giovannucci said. “We were better able to look at consistent long-term activity and saw there was no harm.”

The study included 116,221 participants in the Nurses’ Health Study and the Health Professionals Follow-up Study between 1988 and 2018, who completed up to 15 (median, 11) questionnaires on their health and leisure-time physical activity that were updated every 2 years.

Most were White (96%), 63% were female, and the average age and body mass index over follow-up was 66 years and 26 kg/m². During 30 years of follow-up, there were 47,596 deaths.
 

‘Any effort is worthwhile’

The analysis found that individuals who met the guideline for long-term vigorous physical activity (75-150 min/week) cut their adjusted risk of death from cardiovascular disease (CVD) by a whopping 31%, from non-CVD causes by 15%, and all-causes by 19%, compared with those with no long-term vigorous activity.

Those completing two to four times the recommended minimum (150-299 min/week) had a 27%-33% lower risk of CVD mortality, 19% lower risk of non-CVD mortality, and 21%-23% lower risk of all-cause mortality.

Higher levels did not appear to further lower mortality risk. For example, 300-374 min/week of vigorous physical activity was associated with a 32% lower risk of CVD death, 18% lower risk of non-CVD death, and 22% lower risk of dying from any cause.

The analysis also found that individuals who met the guidelines for moderate physical activity had lower CVD, non-CVD, and all-cause mortality risks whether they were active 150-244 min/week (22%, 19%, and 20%, respectively) or 225-299 min/week (21%, 25%, and 20%, respectively), compared with those with almost no long-term moderate activity.

Those fitting in two to four times the recommended minimum (300-599 min/week) had a 28%-38% lower risk of CVD mortality, 25%-27% lower risk of non-CVD mortality, and 26%-31% lower risk of all-cause mortality.

The mortality benefit appeared to plateau, with 600 min/week of moderate physical activity showing associations similar to 300-599 min/week.

“The sweet spot seems to be two to four times the recommended levels but for people who are sedentary, I think one of the key messages that I give my patients is that any effort is worthwhile; that any physical activity, even less than the recommended, has some mortality reduction,” Erin Michos, MD, MHS, associate director of preventive cardiology at Johns Hopkins University, Baltimore, said in an interview.

Indeed, individuals who reported doing just 20-74 minutes of moderate exercise per week had a 19% lower risk of dying from any cause and a 13% lower risk of dying from CVD compared with those doing less.

Current American Heart Association (AHA) recommendations are for at least 150 minutes per week of moderate-intensity aerobic exercise or 75 minutes per week of vigorous aerobic exercise, or a combination of both.

“This suggests that even more is probably better, in the range of two to four times that, so maybe we should move our targets a little bit higher, which is kind of what the Department of Health and Human Services has already done,” said Dr. Michos, who was not involved in the study.

Former AHA president Donna K. Arnett, PhD, who was not involved in the study, said in a statement that “we’ve known for a long time that moderate or intense levels of physical exercise can reduce a person’s risk of both atherosclerotic cardiovascular disease and mortality.

“We have also seen that getting more than 300 minutes of moderate-intensity aerobic physical activity or more than 150 minutes of vigorous-intensity aerobic physical exercise each week may reduce a person’s risk of atherosclerotic cardiovascular disease even further, so it makes sense that getting those extra minutes of exercise may also decrease mortality,” she added.
 

Mix and match

Dr. Giovannucci noted that the joint effects of the two types of exercise on mortality have not been studied and “there are some questions, for example, about whether doing a lot of moderate activity is sufficient or can you get more benefits by doing vigorous activity also.”

Joint analyses of both exercise intensities found that additional vigorous physical activity was associated with lower mortality among participants with insufficient (less than 300 min/week) levels of moderate exercise but not among those with at least 300 min/week of moderate exercise.

“The main message is that you can get essentially all of the benefit by just doing moderate exercise,” Dr. Giovannucci said. “There’s no magic benefit of doing vigorous [exercise]. But if someone wants to do vigorous, they can get the benefit in about half the time. So if you only have 2-3 hours a week to exercise and can do, say 2 or 3 hours of running, you can get pretty much the maximum benefit.”

Sensitivity analyses showed a consistent association between long-term leisure physical activity and mortality without adjustment for body mass index/calorie intake.

“Some people think the effect of exercise is to lower your body weight or keep it down, which could be one of the benefits, but even independent of that, you get benefits even if it has no effect on your weight,” he said. “So, definitely, that’s important.”

Dr. Michos pointed out that vigorous physical activity may seem daunting for many individuals but that moderate exercise can include activities such as brisk walking, ballroom dancing, active yoga, and recreational swimming.

“The nice thing is that you can really combine or substitute both and get just as similar mortality reductions with moderate physical activity, because a lot of patients may not want to do vigorous activity,” she said. “They don’t want to get on the treadmill; that’s too intimidating or stressful.”

The study was supported by the National Institutes of Health. The authors and Dr. Michos report no relevant financial relationships.

A version of this article first appeared on Medscape.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. Well after people recover from acute COVID infections, they can still have a wide range of lingering symptoms, including depression, anxiety, brain fog, and PTSD.

courtesy Oregon Health & Science University

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. Well after people recover from acute COVID infections, they can still have a wide range of lingering symptoms, including depression, anxiety, brain fog, and PTSD.

courtesy Oregon Health & Science University

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. Well after people recover from acute COVID infections, they can still have a wide range of lingering symptoms, including depression, anxiety, brain fog, and PTSD.

courtesy Oregon Health & Science University

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.

Biologic agents may not be as safe or effective in Hispanic patients with inflammatory bowel disease (IBD) as they are in non-Hispanic patients, suggest new data published online in Clinical Gastroenterology and Hepatology.

To compare risk for hospitalization, surgery, and serious infections, Nghia H. Nguyen, MD, and his team at the Inflammatory Bowel Disease Center at the University of California, San Diego, included a multicenter, electronic health record–based cohort of biologic-treated Hispanic and non-Hispanic patients with IBD and used 1:4 propensity score matching.

They compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% treated with tumor necrosis factor alpha [TNF-alpha] antagonist; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% treated with TNF-alpha antagonist; 27% with prior biologic exposure). Patients were new users of biologics (TNF-alpha antagonist, ustekinumab, or vedolizumab).

Compared with non-Hispanic patients, Hispanic patients had a higher risk for all-cause hospitalization (31% vs. 23%) within 1 year of starting a biologic agent.

Hispanic patients also had almost twice the risk for IBD-related surgeries (7% vs. 4.6%, respectively) and trended toward a higher risk for serious infection (8.8% vs. 4.9%, respectively).

The findings are particularly important because incidence and prevalence of IBD in Hispanic adults are increasing rapidly, according to the authors.

“Currently, 1.2% of Hispanic adults in the United States report having IBD, and this number is expected to increase progressively over the next few years with global immigration patterns and changing demographics of the United States,” the authors write.
 

Potential drivers of disparities

Hispanic patients have been underrepresented in clinical trials of biologic agents in IBD, making up fewer than 5% of participants, the authors note. This has resulted in limited data and created challenges in discerning reasons for the disparity.

The authors note the potential role of genetics in the effectiveness of some biologic agents, although that has not been well studied in Hispanic patients.

Additionally, according to this study, Hispanic patients with IBD lived with more negative social determinants of health, particularly related to food insecurity (27%) and lack of adequate social support (83%), compared with non-Hispanic patients (unpublished data).

“In other studies on health care utilization, Hispanic patients were found to have limited access to appropriate specialist care and lack of insurance coverage,” the authors point out.

The authors acknowledge that limitations of their study include the inability to pinpoint the primary reason for hospitalization because data on primary versus secondary discharge diagnoses were not available. Also, they relied on prescription information in electronic health records and could not confirm that medications were dispensed or that patients took them.

They also acknowledged selection bias as a limitation, because the focus was only on patients treated with biologics and not on outcomes for those who may have warranted a biologic treatment but were unable to receive it.

“Future studies are needed to investigate the biological, social, and environmental drivers of these differences,” the authors write.

The authors’ complete financial disclosures are available with the full text of the paper.

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

Biologic agents may not be as safe or effective in Hispanic patients with inflammatory bowel disease (IBD) as they are in non-Hispanic patients, suggest new data published online in Clinical Gastroenterology and Hepatology.

To compare risk for hospitalization, surgery, and serious infections, Nghia H. Nguyen, MD, and his team at the Inflammatory Bowel Disease Center at the University of California, San Diego, included a multicenter, electronic health record–based cohort of biologic-treated Hispanic and non-Hispanic patients with IBD and used 1:4 propensity score matching.

They compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% treated with tumor necrosis factor alpha [TNF-alpha] antagonist; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% treated with TNF-alpha antagonist; 27% with prior biologic exposure). Patients were new users of biologics (TNF-alpha antagonist, ustekinumab, or vedolizumab).

Compared with non-Hispanic patients, Hispanic patients had a higher risk for all-cause hospitalization (31% vs. 23%) within 1 year of starting a biologic agent.

Hispanic patients also had almost twice the risk for IBD-related surgeries (7% vs. 4.6%, respectively) and trended toward a higher risk for serious infection (8.8% vs. 4.9%, respectively).

The findings are particularly important because incidence and prevalence of IBD in Hispanic adults are increasing rapidly, according to the authors.

“Currently, 1.2% of Hispanic adults in the United States report having IBD, and this number is expected to increase progressively over the next few years with global immigration patterns and changing demographics of the United States,” the authors write.
 

Potential drivers of disparities

Hispanic patients have been underrepresented in clinical trials of biologic agents in IBD, making up fewer than 5% of participants, the authors note. This has resulted in limited data and created challenges in discerning reasons for the disparity.

The authors note the potential role of genetics in the effectiveness of some biologic agents, although that has not been well studied in Hispanic patients.

Additionally, according to this study, Hispanic patients with IBD lived with more negative social determinants of health, particularly related to food insecurity (27%) and lack of adequate social support (83%), compared with non-Hispanic patients (unpublished data).

“In other studies on health care utilization, Hispanic patients were found to have limited access to appropriate specialist care and lack of insurance coverage,” the authors point out.

The authors acknowledge that limitations of their study include the inability to pinpoint the primary reason for hospitalization because data on primary versus secondary discharge diagnoses were not available. Also, they relied on prescription information in electronic health records and could not confirm that medications were dispensed or that patients took them.

They also acknowledged selection bias as a limitation, because the focus was only on patients treated with biologics and not on outcomes for those who may have warranted a biologic treatment but were unable to receive it.

“Future studies are needed to investigate the biological, social, and environmental drivers of these differences,” the authors write.

The authors’ complete financial disclosures are available with the full text of the paper.

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

Biologic agents may not be as safe or effective in Hispanic patients with inflammatory bowel disease (IBD) as they are in non-Hispanic patients, suggest new data published online in Clinical Gastroenterology and Hepatology.

To compare risk for hospitalization, surgery, and serious infections, Nghia H. Nguyen, MD, and his team at the Inflammatory Bowel Disease Center at the University of California, San Diego, included a multicenter, electronic health record–based cohort of biologic-treated Hispanic and non-Hispanic patients with IBD and used 1:4 propensity score matching.

They compared 240 Hispanic patients (53% male; 45% with ulcerative colitis; 73% treated with tumor necrosis factor alpha [TNF-alpha] antagonist; 20% with prior biologic exposure) with 960 non-Hispanic patients (51% male; 44% with ulcerative colitis; 67% treated with TNF-alpha antagonist; 27% with prior biologic exposure). Patients were new users of biologics (TNF-alpha antagonist, ustekinumab, or vedolizumab).

Compared with non-Hispanic patients, Hispanic patients had a higher risk for all-cause hospitalization (31% vs. 23%) within 1 year of starting a biologic agent.

Hispanic patients also had almost twice the risk for IBD-related surgeries (7% vs. 4.6%, respectively) and trended toward a higher risk for serious infection (8.8% vs. 4.9%, respectively).

The findings are particularly important because incidence and prevalence of IBD in Hispanic adults are increasing rapidly, according to the authors.

“Currently, 1.2% of Hispanic adults in the United States report having IBD, and this number is expected to increase progressively over the next few years with global immigration patterns and changing demographics of the United States,” the authors write.
 

Potential drivers of disparities

Hispanic patients have been underrepresented in clinical trials of biologic agents in IBD, making up fewer than 5% of participants, the authors note. This has resulted in limited data and created challenges in discerning reasons for the disparity.

The authors note the potential role of genetics in the effectiveness of some biologic agents, although that has not been well studied in Hispanic patients.

Additionally, according to this study, Hispanic patients with IBD lived with more negative social determinants of health, particularly related to food insecurity (27%) and lack of adequate social support (83%), compared with non-Hispanic patients (unpublished data).

“In other studies on health care utilization, Hispanic patients were found to have limited access to appropriate specialist care and lack of insurance coverage,” the authors point out.

The authors acknowledge that limitations of their study include the inability to pinpoint the primary reason for hospitalization because data on primary versus secondary discharge diagnoses were not available. Also, they relied on prescription information in electronic health records and could not confirm that medications were dispensed or that patients took them.

They also acknowledged selection bias as a limitation, because the focus was only on patients treated with biologics and not on outcomes for those who may have warranted a biologic treatment but were unable to receive it.

“Future studies are needed to investigate the biological, social, and environmental drivers of these differences,” the authors write.

The authors’ complete financial disclosures are available with the full text of the paper.

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

During the pandemic, Native Americans’ life expectancy dropped more than in any other racial or ethnic group. Essentially, they lost nearly 5 years. And they already had the lowest life expectancy of any racial or ethnic group.

Researchers from the University of Colorado-Boulder, the Urban Institute, and Virginia Commonwealth University compared life expectancy changes during 2019-2021 in the United States and 21 peer countries. The study is the first to estimate such changes in non-Hispanic American Indian/Alaska Native and Asian populations. The researchers were taken aback by their findings.

In those 2 years, Americans overall saw a net loss of 2.41 years: Life expectancy declined from 78.85 years in 2019 to 76.98 years in 2020 and 76.44 in 2021. Surprisingly, peer countries not only saw a much smaller loss (0.55 year), but actually had an increase of 0.26 year between 2020 and 2021. The US decline was 8.5 times greater than that of the average decline among 16 other high-income countries during the same period. “It’s like nothing we have seen since World War II,” said Dr. Steven Woolf, one of the coauthors of the study.

The decrease in life expectancy—or, put another way, mortality—was “highly racialized” in the United States, the researchers say. The largest drops in 2020 were among non-Hispanic American Indian/Alaska Native (4.48 years), Hispanic (3.72 years), non-Hispanic Black (3.20 years), and non-Hispanic Asian (1.83 years) populations. In 2021, the largest decreases were in the non-Hispanic White population. The reasons for the “surprising crossover” in outcomes are not entirely clear, the researchers say, and likely have multiple explanations.

However, the patterns, they note, “reflect a long history of systemic racism” and “inadequacies in how the pandemic was managed in the United States.” In a university news release, study coauthor Ryan Masters, PhD, said, “The US didn’t take COVID seriously to the extent that other countries did, and we paid a horrific price for it, with Black and brown people suffering the most.”

The researchers expected to see a decline among Native Americans, Masters said, because they often lack access to vaccines, quality health care, and transportation. But the magnitude of the drop in life expectancy was “shocking.” He added, “You just don’t see numbers like this in advanced countries in the modern day.”

Noting that the troubling downward trend in life expectancy had been on view even before the pandemic, Masters said, “This isn’t just a COVID problem. There are broader social and economic policies that placed the United States at a disadvantage long before this pandemic. The time to address them is long overdue.”

During the pandemic, Native Americans’ life expectancy dropped more than in any other racial or ethnic group. Essentially, they lost nearly 5 years. And they already had the lowest life expectancy of any racial or ethnic group.

Researchers from the University of Colorado-Boulder, the Urban Institute, and Virginia Commonwealth University compared life expectancy changes during 2019-2021 in the United States and 21 peer countries. The study is the first to estimate such changes in non-Hispanic American Indian/Alaska Native and Asian populations. The researchers were taken aback by their findings.

In those 2 years, Americans overall saw a net loss of 2.41 years: Life expectancy declined from 78.85 years in 2019 to 76.98 years in 2020 and 76.44 in 2021. Surprisingly, peer countries not only saw a much smaller loss (0.55 year), but actually had an increase of 0.26 year between 2020 and 2021. The US decline was 8.5 times greater than that of the average decline among 16 other high-income countries during the same period. “It’s like nothing we have seen since World War II,” said Dr. Steven Woolf, one of the coauthors of the study.

The decrease in life expectancy—or, put another way, mortality—was “highly racialized” in the United States, the researchers say. The largest drops in 2020 were among non-Hispanic American Indian/Alaska Native (4.48 years), Hispanic (3.72 years), non-Hispanic Black (3.20 years), and non-Hispanic Asian (1.83 years) populations. In 2021, the largest decreases were in the non-Hispanic White population. The reasons for the “surprising crossover” in outcomes are not entirely clear, the researchers say, and likely have multiple explanations.

However, the patterns, they note, “reflect a long history of systemic racism” and “inadequacies in how the pandemic was managed in the United States.” In a university news release, study coauthor Ryan Masters, PhD, said, “The US didn’t take COVID seriously to the extent that other countries did, and we paid a horrific price for it, with Black and brown people suffering the most.”

The researchers expected to see a decline among Native Americans, Masters said, because they often lack access to vaccines, quality health care, and transportation. But the magnitude of the drop in life expectancy was “shocking.” He added, “You just don’t see numbers like this in advanced countries in the modern day.”

Noting that the troubling downward trend in life expectancy had been on view even before the pandemic, Masters said, “This isn’t just a COVID problem. There are broader social and economic policies that placed the United States at a disadvantage long before this pandemic. The time to address them is long overdue.”

During the pandemic, Native Americans’ life expectancy dropped more than in any other racial or ethnic group. Essentially, they lost nearly 5 years. And they already had the lowest life expectancy of any racial or ethnic group.

Researchers from the University of Colorado-Boulder, the Urban Institute, and Virginia Commonwealth University compared life expectancy changes during 2019-2021 in the United States and 21 peer countries. The study is the first to estimate such changes in non-Hispanic American Indian/Alaska Native and Asian populations. The researchers were taken aback by their findings.

In those 2 years, Americans overall saw a net loss of 2.41 years: Life expectancy declined from 78.85 years in 2019 to 76.98 years in 2020 and 76.44 in 2021. Surprisingly, peer countries not only saw a much smaller loss (0.55 year), but actually had an increase of 0.26 year between 2020 and 2021. The US decline was 8.5 times greater than that of the average decline among 16 other high-income countries during the same period. “It’s like nothing we have seen since World War II,” said Dr. Steven Woolf, one of the coauthors of the study.

The decrease in life expectancy—or, put another way, mortality—was “highly racialized” in the United States, the researchers say. The largest drops in 2020 were among non-Hispanic American Indian/Alaska Native (4.48 years), Hispanic (3.72 years), non-Hispanic Black (3.20 years), and non-Hispanic Asian (1.83 years) populations. In 2021, the largest decreases were in the non-Hispanic White population. The reasons for the “surprising crossover” in outcomes are not entirely clear, the researchers say, and likely have multiple explanations.

However, the patterns, they note, “reflect a long history of systemic racism” and “inadequacies in how the pandemic was managed in the United States.” In a university news release, study coauthor Ryan Masters, PhD, said, “The US didn’t take COVID seriously to the extent that other countries did, and we paid a horrific price for it, with Black and brown people suffering the most.”

The researchers expected to see a decline among Native Americans, Masters said, because they often lack access to vaccines, quality health care, and transportation. But the magnitude of the drop in life expectancy was “shocking.” He added, “You just don’t see numbers like this in advanced countries in the modern day.”

Noting that the troubling downward trend in life expectancy had been on view even before the pandemic, Masters said, “This isn’t just a COVID problem. There are broader social and economic policies that placed the United States at a disadvantage long before this pandemic. The time to address them is long overdue.”

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

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

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

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

Single ulcers, anal lesions, and mouth sores are all unique symptoms of the current monkeypox outbreak, according to the largest international monkeypox case series to date. These findings underscore the need to broaden case definitions for the disease, researchers say.

“While we expected various skin problems and rashes, we also found that 1 in 10 people had only a single skin lesion in the genital area, and 15% had anal and/or rectal pain,” John Thornhill, MD, PhD, the lead author of the research, said in a press release. Dr. Thornhill is a consultant physician in sexual health and HIV and a clinical senior lecturer at Barts NHS Health Trust and Queen Mary University of London. “These different presentations highlight that monkeypox infections could be missed or easily confused with common sexually transmitted infections such as syphilis or herpes,” he said.

Since April 2022, more than 15,000 cases of monkeypox have been reported in 66 countries where the virus was previously not known to be present. The virus, a less severe cousin of smallpox, is endemic to areas of central and west Africa. In the current outbreak, infections have overwhelmingly been found in men who have sex with men.

In a study published in the New England Journal of Medicine, researchers reported clinical details and outcomes of 528 monkeypox infections across 16 countries. All the cases were diagnosed between April 27 and June 24, 2022. Ninety-five percent of the cases were suspected to have been transmitted through sexual activity, 98% of patients identified as gay or bisexual men, and 75% of the patients were White. The median age of patients in this case series was 38 years, and 90% of infections occurred in Europe. Forty-one percent of patients were HIV-positive, and 96% of these individuals were receiving antiretroviral therapy. Among patients whose HIV status was negative or unknown, 57% reported using preexposure prophylaxis against HIV. About 3 in 10 (29%) individuals tested positive for concurrent sexually transmitted infections.

Nearly three out of four patients (73%) had anogenital lesions, and 41% had mucosal lesions. Fifty-four patients had one genital lesion, and 64% had fewer than 10 lesions in total. Fever (62%), swollen lymph nodes (56%), lethargy (41%), and myalgia (31%) were commonly reported symptoms prior to the development of the rash. Seventy patients (13%) required hospitalization, most commonly for severe anorectal pain and soft-tissue superinfection. Just 5% of patients received monkeypox-specific treatment: intravenous or topical cidofovir (2%), tecovirimat (2%), and vaccinia immune globulin (<1%).

The study “importantly reinforces our current understanding that the overwhelming majority of cases have been sexually associated, predominantly in men who have sex with men,” Jeffrey Klausner, MD, PhD, an infectious disease specialist at the University of Southern California, Los Angeles, said in an interview with this news organization. He was not involved with the research. “Anyone can get monkeypox, but it is most effectively spread through what we call dense networks – where there is a frequent, close personal contact,” he said. “It just happens that gay men and other men who have sex with men have some of those networks.”

The fact that most lesions are present in the genital and anal region – which is unique to this outbreak – points to transmission of the infection during intimate contact, he noted. Still, there is not enough evidence to suggest that monkeypox is spread through sexual transmission. While most semen samples in the study tested positive for monkeypox viral DNA, it is not known whether there is enough virus present to cause transmission, Dr. Thornhill said. He noted that more research is needed.

Dr. Klausner also emphasized the importance of developing new tests to diagnose monkeypox earlier to prevent spread. The lab test for monkeypox requires a swab from a lesion, but this study showed that most patients had notable symptoms prior to developing the standard rash or lesions, he said. Reliable tests using saliva or throat swabs could help detect infections faster, he noted. Patients are thought to be most contagious when they develop lesions, Dr. Klausner said, so diagnosing patients before this stage would allow them to be isolated sooner.

The California-based lab company Flow Health announced a saliva-based PCR test for monkeypox on July 9, although the Food and Drug Administration cautioned that test results from other sample types beside lesion swabs may be inaccurate. “The FDA is not aware of clinical data supporting the use of other sample types, such as blood or saliva, for monkeypox virus testing,” the agency said in a statement on July 15. “Testing samples not taken from a lesion may lead to false test results.”

Dr. Klausner reports no relevant financial relationships.

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

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

A version of this article first appeared on Medscape.com

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

A version of this article first appeared on Medscape.com

Editor’s Note: The study covered in this summary was published on ResearchSquare.com as a preprint and has not yet been peer reviewed.

Key takeaway

Maladaptive schemas (entitlement, vulnerability, and emotional deprivation) and cognitive evaluation systems (self-esteem and systemizing-empathizing) are associated with grandiose and vulnerable narcissism.

Why this matters

The cognitive features and phenotypic diversity of narcissism subtypes are partially unknown.

This study integrates both grandiose and vulnerable narcissism into a common framework with cognitive components connected to these traits.
 

Study design

This study enrolled 478 participants (397 female and 4 did not reveal their gender).

The average age of participants was 35 years (standard deviation, 14.97), with a range of 18-76 years.

A 25-item version of the Narcissistic Personality Inventory (NPI), a 40-item self-report measure of narcissism traits, was used to assess the level of authority, grandiose exhibitionism, and entitlement/exploitativeness characteristics of study participants.

The Maladaptive Covert Narcissism Scale, an expanded version of the 23-item self-report Hypersensitive Narcissism Scale, was used to assess the level of hypersensitivity, vulnerability, and entitlement of study participants.

The Rosenberg Self-Esteem Scale, a 10-item self-report scale, was used to assess the level of self-esteem of study participants.

The Young Schema Questionnaire is a 244-item measure of 19 different maladaptive schemas and was used to observe Emotional Deprivation, Vulnerability to Harm and Illness, and Entitlement schemas of study participants.

The Empathizing Quotient is a self-report measure and was used to assess the emotional intelligence of study participants.
 

Key results

Moderate correlation between grandiose and vulnerable narcissism and the Entitlement schema was observed.

A moderate/strong connection was observed between vulnerable narcissism and the Vulnerability to Harm and Illness schema and a moderate connection with the Emotional Deprivation schema.

No significant correlation was observed between grandiose narcissism and the Emotional Deprivation schema.

A moderate, negative correlation between vulnerable narcissism and emotional skills was observed.

A positive, weak connection between grandiose narcissism and self-esteem; and a negative, moderate connection between vulnerable narcissism and self-esteem were observed.

Gender and age were associated with empathic skills, and age was weakly/moderately connected with self-esteem and vulnerable narcissism.
 

Limitations

This was a cross-sectional analysis investigating a temporally specific state of personality and cognitive functioning.

The gender ratio was shifted toward women in this study.

Conclusions drawn from connections between observed components are interchangeable and cause/effect connections cannot be discerned.
 

Disclosures

The study was supported by the National Research, Development, and Innovation Office (Grant No. NRDI–138040) and by the Human Resource Development Operational Program – Comprehensive developments at the University of Pécs for the implementation of intelligent specialization (EFOP-3.6.1-16-2016-00004). First author Dorian Vida’s work was supported by the Collegium Talentum Programme of Hungary. None of the authors disclosed any competing interests.

This is a summary of a preprint research study, “In the mind of Narcissus: the mediating role of emotional regulation in the emergence of distorted cognitions,” written by Dorian Vida from the University of Pécs, Hungary and colleagues on ResearchSquare.com. This study has not yet been peer reviewed. The full text of the study can be found on ResearchSquare.com.

A version of this article first appeared on Medscape.com

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Adults with hypertension who were vaccinated for COVID-19 with at least one booster were more than twice as likely as vaccinated and boosted individuals without hypertension to be hospitalized for severe COVID-19, according to data from more than 900 individuals.

“We were surprised to learn that many people who were hospitalized with COVID-19 had hypertension and no other risk factors,” said Susan Cheng, MD, MPH, director of the Institute for Research on Healthy Aging in the department of cardiology at the Smidt Heart Institute, Los Angeles, and a senior author of the study. “This is concerning when you consider that almost half of American adults have high blood pressure.”

Vishnu Kumar/Thinkstock

COVID-19 vaccines demonstrated ability to reduce death and some of the most severe side effects from the infection in the early stages of the pandemic. Although the Omicron surge prompted recommendations for a third mRNA vaccine dose, “a proportion of individuals who received three mRNA vaccine doses still required hospitalization for COVID-19 during the Omicron surge,” and the characteristics associated with severe illness in vaccinated and boosted patients have not been explored, Joseph Ebinger, MD, of Cedars-Sinai Medical Center, Los Angeles, and colleagues wrote.

Previous research has shown an association between high blood pressure an increased risk for developing severe COVID-19 compared to several other chronic health conditions, including kidney disease, type 2 diabetes, chronic obstructive pulmonary disease, and heart failure, the researchers noted.

In a study published in Hypertension, the researchers identified 912 adults who received at least three doses of mRNA COVID-19 vaccine and were later diagnosed with COVID-19 during the surge in infections from the Omicron variant between December 2021 and April 2022.

A total of 145 of the individuals were hospitalized (16%); of these, 125 (86%) had hypertension.

Patients with hypertension were the most likely to be hospitalized, with an odds ratio of 2.9. In addition to high blood pressure, factors including older age (OR, 1.3), chronic kidney disease (OR, 2.2), prior myocardial infarction or heart failure (OR, 2.2), and longer time since the last vaccination and COVID-19 infection were associated with increased risk of hospitalization in a multivariate analysis.

However, the increased risk of severe illness and hospitalization associated with high blood pressure persisted, with an OR of 2.6, in the absence of comorbid conditions such as type 2 diabetes, kidney disease, and heart failure, the researchers emphasized.

“Although the mechanism for hypertension-associated COVID-19 risk remains unclear, prior studies have identified delayed SARS-CoV-2 viral clearance and prolonged inflammatory response among hypertensive patients, which may contribute to greater disease severity,” they wrote.

The findings were limited by several factors, including the use of data from a single center and lack of information on which Omicron variants and subvariants were behind the infections, the researchers noted.

However, the results highlight the need for more research on how to reduce the risks of severe COVID-19 in vulnerable populations, and on the mechanism for a potential connection between high blood pressure and severe COVID-19, they said.

Given the high prevalence of hypertension worldwide, increased understanding of the hypertension-specific risks and identification of individual and population-level risk reduction strategies will be important to the transition of COVID-19 from pandemic to endemic, they concluded.
 

Omicron changes the game

“When the pandemic initially started, many conditions were seen to increase risk for more severe COVID illness, and hypertension was one of those factors – and then things changed,” lead author Dr. Ebinger said in an interview. “First, vaccines arrived on the scene and substantially reduced risk of severe COVID for everyone who received them. Second, Omicron arrived and, while more transmissible, this variant has been less likely to cause severe COVID. On the one hand, we have vaccines and boosters that we want to think of as ‘the great equalizer’ when it comes to preexisting conditions. On the other hand, we have a dominant set of SARS-CoV-2 subvariants that seem less virulent in most people.

“Taken together, we have been hoping and even assuming that we have been doing pretty well with minimizing risks. Unfortunately, our study results indicate this is not exactly the case,” he said.

“Although vaccines and boosters appear to have equalized or minimized the risks of severe COVID for some people, this has not happened for others – even in the setting of the milder Omicron variant. Of individuals who were fully vaccinated and boosted, having hypertension increased the odds of needing to be hospitalized after getting infected with Omicron by 2.6-fold, even when accounting for or in the absence of having any major chronic disease that might otherwise predispose to more severe COVID-19 illness,” Dr. Ebinger added.

“So, while the originally seen risks of having obesity or diabetes seem to have been minimized during this current era of pandemic, the risk of having hypertension has persisted. We found this both surprising and concerning, because hypertension is very common and present in over half of people over age 50.”

Surprisingly, “we found that a fair number of people, even after being fully vaccinated plus a having gotten a booster, will not only catch Omicron but get sick enough to need hospital care,” Dr. Ebinger emphasized. “Moreover, it is not just older adults with major comorbid conditions who are vulnerable. Our data show that this can happen to an adult of any age and especially if a person has only hypertension and otherwise no major chronic disease.”

The first takeaway message for clinicians at this time is to raise awareness, Dr. Ebinger stressed in the interview. “We need to raise understanding around the fact that receiving three doses of vaccine may not prevent severe COVID-19 illness in everyone, even when the circulating viral variant is presumed to be causing only mild disease in most people. Moreover, the people who are most at risk are not whom we might think they are. They are not the sickest of the sick. They include people who might not have major conditions such as heart disease or kidney disease, but they do have hypertension.”

Second, “we need more research to understand out why there is this link between hypertension and excess risk for the more severe forms of COVID-19, despite it arising from a supposedly milder variant,” said Dr. Ebinger.

“Third, we need to determine how to reduce these risks, whether through more tailored vaccine regimens or novel therapeutics or a combination approach,” he said.

Looking ahead, “the biological mechanism underpinning the association between hypertension and severe COVID-19 remains underexplored. Future work should focus on understanding the factors linking hypertension to severe COVID-19, as this may elucidate both information on how SARS-CoV-2 effects the body and potential targets for intervention,” Dr. Ebinger added.

The study was supported in part by Cedars-Sinai Medical Center, the Erika J. Glazer Family Foundation and the National Institutes of Health. The researchers had no financial conflicts to disclose.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

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.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

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.

Researchers have developed a hypothesis that may explain how chronic neuroinflammation contributes to conditions such as myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postacute sequelae of SARS-CoV-2 infection through a continuing relapse-recovery cycle.

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.

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

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

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

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

Wide variation in the cost of common cardiovascular (CV) tests and procedures, from stress tests to coronary interventions, was revealed in a cross-sectional analysis based on publicly available data from 20 top-ranked hospitals in the United States.

The analysis also suggested a low level of compliance with the 2021 Hospital Price Transparency Final Rule among the 20 centers.

“The variation we found in payer-negotiated prices for identical cardiovascular tests and procedures was stunning,” Rishi K. Wadhera, MD, MPP, MPhil, Beth Israel Deaconess Medical Center, Boston, told this news organization.

KatarzynaBialasiewicz/Thinkstock

Difficulties with data, interpretation

The researchers looked at payer and self-pay cash prices for noninvasive and invasive CV tests and procedures at the U.S. News & World Report 2021 top 20–ranked U.S. hospitals, based in part on Current Procedural Terminology codes.

Price differences among the hospitals were derived from median negotiated prices for each test and procedure at the centers across all payers. The interquartile ratio (IQR) of prices for each test or procedure across payers was used to evaluate within-hospital price variation.

“Only 80% of the hospitals reported prices for some cardiovascular tests and procedures,” Dr. Wadhera said. “For the most part, even among the hospitals that did report this information, it was extremely challenging to navigate and interpret the data provided.”

Further, the team found that only 7 of the 20 hospitals reported prices for all CV tests and procedures. Centers that did not post prices for some tests or procedures are named in the report’s Figure 1 and Figure 2.

The number of insurance plans listed for each test or procedure ranged from 1 to 432 in the analysis. Median prices ranged from $204 to $2,588 for an echocardiogram, $463 to $3,230 for a stress test, $2,821 to $9,382 for right heart catheterization, $2,868 to $9,203 for a coronary angiogram, $657 to $25,521 for a PCI, and $506 to $20,002 for pacemaker implantation, the report states.

A similar pattern was seen for self-pay cash prices.

Within-hospital variation also ranged broadly. For example, the widest IQR ranges were $3,143-$12,926 for a right heart catheterization, $4,011-$14,486 for a coronary angiogram, $11,325-$23,392 for a PCI, and $8,474-$22,694 for pacemaker implantation.

The report cites a number of limitations to the analysis, among those, the need to rely on the hospitals themselves for data quality and accuracy.
 

‘More needed besides transparency’

“As a means to better understand health care costs, many opined that full price transparency would leverage market dynamics and result in lower costs,” observed Clyde W. Yancy, MD, MSc, professor of medicine and chief of cardiology at Northwestern Medicine, Chicago. The findings “by an expert group of outcomes scientists make clear that more is needed besides price transparency to lower cost,” he said in an interview.

That said, he added, “there are sufficient variations and allowances made for data collection that it is preferable to hold the current findings circumspect at best. Importantly, the voice of the hospitals does not appear.”

Although “price variation among the top 20 hospitals is substantial,” he observed, “without a better assessment of root cause, actual charge capture, prevailing market dynamics – especially nursing and ancillary staff costs – and the general influence of inflation, it is too difficult to emerge with a precise interpretation.”

Across the 20 hospitals, “there are likely to be 20 different business models,” he added, with negotiated prices reflecting “at least regional, if not institutional, variations.”

“These are complex issues. The several-fold price differences in standard procedures are a concern and an area worth further study with the intention of lowering health care costs,” Dr. Yancy said. “But clearly our next efforts should not address lowering prices per se but understanding how prices are set [and] the connection with reimbursement and actual payments.”

Dr. Wadhera discloses receiving personal fees from Abbott and CVS Health unrelated to the current study; disclosures for the other authors are in the report. Dr. Yancy is deputy editor of JAMA Cardiology.

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

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

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.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

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.

A U.S. study describes the immune response to COVID-19 infection that damages the brain’s blood vessels and may lead to short- and long-term neurologic symptoms.

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.