Long COVID

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Symptom timelines surrounding COVID infection tend to center on either the immediate 5-day quarantine protocols for acute infection or the long-COVID symptoms that can last a month or potentially far longer.

But some patients report a “middle-range” COVID that will resolve before it becomes long COVID, yet still lasts longer than is typical for viral infections. People may return to work or daily routines, but something is off: What had been simple exercise regimens become onerous. Everyday tasks take more effort.

Does this ill-defined subset point to a “medium COVID?”

Farha Ikramuddin, MD, MHA, a physiatrist and rehabilitation specialist at the University of Minnesota and M Health Fairview in Minneapolis, points out there is no definition or diagnostic code or shared official understanding of a middle category for COVID.

“But am I seeing that? Absolutely,” she said in an interview.

“I have seen patients who are younger, healthier, [and] with not so many comorbidities have either persistence of symptoms or reappearance after the initial infection is done,” she said.

Some patients report they had very low infection or were nonsymptomatic and returned to their normal health fairly quickly after infection. Then a week later they began experiencing fatigue, lost appetite, loss of smell, and feeling full after a few bites, Dr. Ikramuddin said.

Part of the trouble in categorizing the space between returning to normal after a week and having symptoms for months is that organizations can’t agree on a timeline for when symptoms warrant a “long-COVID” label.

For instance, the Centers for Disease Control and Prevention defines it as 4 or more weeks after infection. The World Health Organization defines it as starting 3 months after COVID-19 symptom onset.

“I’m seeing ‘medium COVID’ – as one would call it – in younger and healthier patients. I’m also noticing that these symptoms are not severe enough to warrant stopping their job or changing their job schedules,” Dr. Ikramuddin said.

They go back to work, she said, but start noticing something is off.

“I am seeing that.”

“I discharge at least two patients a week from my clinic because they have moved on and no longer have symptoms,” Dr. Ikramuddin said.

In a story from Kaiser Health News published last month, WHYY health reporter Nina Feldman writes: “What I’ve come to think of as my ‘medium COVID’ affected my life. I couldn’t socialize much, drink, or stay up past 9:30 p.m. It took me 10 weeks to go for my first run – I’d been too afraid to try.”

She described a dinner with a friend after ending initial isolation protocols: “One glass of wine left me feeling like I’d had a whole bottle. I was bone-achingly exhausted but couldn’t sleep.”
 

Medical mystery

Dr. Ikramuddin notes the mechanism behind prolonged COVID-19 symptoms is still a medical mystery.

“In one scenario,” she said, “the question is being asked about whether the virus is staying dormant, similar to herpes zoster or HIV.”

“Right now, instead of getting more answers, we’re getting more questions,” Dr. Ikramuddin  said.

Mouhib Naddour, MD, a pulmonary specialist with Sharp HealthCare in San Diego, said he’s seeing that it’s taking some patients who have had COVID longer to recover than it would for other viral infections.

Some patients fall between those recovering within 2-3 weeks and patients having long COVID. Those patients in the gap could be lumped into a middle-range COVID, he told this news organization.

“We try to put things into tables and boxes but it is hard with this disease,” Dr. Naddour said.

He agrees there’s no medical definition for “medium” COVID, but he said the idea should bring hope for patients to know that, if their symptoms are persisting they don’t necessarily have long COVID – and their symptoms may still disappear.

“This is an illness that may take longer to completely recover from,” he said. “The majority of patients we’re seeing in this group could be healthy young patients who get COVID, then 2-3 weeks after they test negative, still have lingering symptoms.”
 

Common symptoms

Some commonly reported symptoms of those with enduring illness, which often overlap with other stages of COVID, are difficulty breathing, chest tightness, dry cough, chest pain, muscle and joint pain, fatigue, difficulty sleeping, and mood swings, Dr. Naddour said. 

“We need to do an extensive assessment to make sure there’s no other problem causing these symptoms,” he said.

Still, there is no set timeline for the medium-COVID range, he noted, so checking in with a primary care physician is important for people experiencing symptoms.
 

It’s a continuum, not a category

Fernando Carnavali, MD, coordinator for Mount Sinai’s Center for Post-COVID Care in New York, said he is not ready to recognize a separate category for a “medium” COVID.

He noted that science can’t even agree on a name for lasting post-COVID symptoms, whether it’s “long COVID” or “long-haul COVID,” “post-COVID syndrome” or “post-acute sequelae of COVID-19 (PASC ).” There’s no agreed-upon pathophysiology or biomarker.

“That creates these gaps of understanding on where we are,” Dr. Carnavali said in an interview.

He said he understands people’s need to categorize symptoms, but rather than a middle ground he sees a continuum.

It doesn’t mean what others may call COVID’s middle ground doesn’t exist, Dr. Carnavali said: “We are in the infancy of defining this. Trying to classify them may create more anxiety.”

The clinicians interviewed for this story report no relevant financial relationships.

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

Even mundane tasks such as making a meal can be exhausting for Louise Salant.

“I’m totally wiped out,” said the 71-year-old former private music instructor with asthma who lives in New York City and has been coping with debilitating symptoms of fatigue, shortness of breath, and gastrointestinal symptoms since recovering from a severe bout of COVID-19 2 years ago. “I just don’t have the energy.”

Ms. Salant is not alone. Many older people who contract COVID-19 experience prolonged symptoms of the disease. An analysis of Medicare Advantage claims data published in the BMJ found that about one-third of roughly 87,000 adults aged 65 in the database with a COVID-19 diagnosis sought care for persistent or new symptoms 21 or more days later.

That figure is about twice the rate of persistent COVID-19 related symptoms seen in a cohort of adults younger than age 65 with commercial insurance analyzed by the same group of researchers in a separate BMJ study. Compared with a 2020 comparator group of patients in this age cohort, these patients had a greater likelihood of respiratory failure, fatigue, hypertension, memory problems, kidney injury, mental health conditions, hypercoagulability, and cardiac rhythm disorders. When they compared post–COVID-19 symptoms to lasting symptoms of another serious viral disease – influenza – the researchers found that only respiratory failure, dementia, and post-viral fatigue were more common in the COVID-19 group.

“It became clear early in the pandemic that there is going to be a second pandemic related to all of the complications that we’ve seen related to COVID-19 infections,” said Ken Cohen, MD, executive director of translational research and national senior medical director for Optum Labs in Minnetonka, Minn., who coauthored the BMJ studies.

The results are among a growing body of evidence suggesting that older adults are at high risk of persistent post-COVID-19 symptoms.

Researchers in Rome, for example, found that 83% of 165 patients aged 65 or older who had been hospitalized for COVID-19 reported at least one lasting symptom – problems like fatigue, shortness of breath, joint pain, and coughing – in the months after hospitalization. One-third of those had two symptoms, and 46% had three or more.

A similar study in Norway found that two-thirds of patients aged 60 or older reported reduced health-related quality of life during follow-up visits 6 months after hospitalization for COVID-19. The most-reported impairments among those patients were the inability to perform the tasks of daily life, reduced mobility, and increased pain and discomfort.
 

Cognitive concerns

Mounting evidence indicates that COVID-19 may contribute to chronic cognitive impairment in older adults. A multisite U.S. study found that 28% of 817 adults presenting to emergency departments with COVID-19 had delirium and poorer outcomes. A Chinese case-control study that enrolled 1,438 individuals hospitalized in Wuhan for COVID-19, along with 438 of their uninfected spouses, found that 12% of COVID-19 survivors experienced cognitive impairment a year after discharge. Matteo Tosato, MD, PhD, head of the outpatient clinic for patients with long COVID symptoms at Gemelli Hospital in Rome, called those findings “very concerning.”

Jin Ho Han, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tenn., said cognitive impairment is common after an acute illness, particularly in frail or vulnerable patients.

“Hospitalization and the acute illness itself accelerate cognitive decline,” said Dr. Han, and previous evidence links delirium with worsening cognition. He and his colleagues are studying the potential role of delirium in longer-term cognitive decline in older patients after COVID-19.

Dr. Han emphasized the importance of preventing COVID-19-related delirium through vaccines and other strategies to reduce exposure of older patients to the virus. “Once you have cognitive decline, there are no interventions to reverse it,” he said.
 

Alarm bells for long-term care

Experts expressed concern that the situation might be even worse for people living in long-term care facilities. Many already need assistance with tasks of daily living and could be particularly vulnerable to lasting effects of COVID-19, said Karl Steinberg, MD, president of the Society for Post-Acute and Long-Term Care Medicine. He estimated that roughly half of his patients who have had COVID-19, regardless of the severity of their symptoms, have endured some degree of functional decline.

“It’s common for long-term care facility residents to experience functional and cognitive decline, even after seemingly minor things, like a cold or a trip to the hospital,” Dr. Steinberg, who has been a medical director of long-term care facilities in San Diego County for more than 2 decades, told this news organization. “It makes it a little harder to determine whether the declines we’ve been seeing post COVID in these residents are attributable to post COVID versus just an accelerated step in their overall expected decline.”

The pandemic may have contributed to worse outcomes for people in long-term care facilities in several ways: the disease itself, its effects on health care delivery, and necessary preventive measures to protect long-term care residents from exposure to the virus.

“During the many months where family visits were prohibited, we saw people – whether they had COVID-19 or not – suffer major clinical, functional, cognitive declines or severe psychological symptoms,” Dr. Steinberg said.

He emphasized the importance of preventive measures such as vaccines and boosters in patients in long-term care facilities. He said the benefit of preventing lasting symptoms is often a strong motivator for family caregivers of people with dementia to get them vaccinated or boosted.

“It’s clear that vaccination and booster reduce the incidence of post-COVID symptoms,” he said. Almost all studies have been in younger cohorts, but he expects the benefits would also apply to older patients.
 

Easing symptoms and offering support

As with long COVID generally, many questions remain about the causes of lasting symptoms of COVID-19 in older patients, and how best to treat them. Dr. Tosato, who led the study of long-COVID patients in Rome, is focusing on inflammation as a critical factor in the condition. He and colleagues across Europe hope to answer some of them by launching a multicenter study of lasting COVID-19 symptoms. 

In the meantime, Dr. Steinberg and Dr. Tosato said they are doing their best to evaluate and treat patients empirically.

“We pull from our armamentarium to treat system-specific symptoms,” Dr. Steinberg said. “We want to improve the quality of life and help each day be the best it can.”

Physicians in long-term care facilities might use medications such as antidepressants or nonpharmacologic approaches for patients experiencing depression symptoms. Families are also crucial in helping patients by bringing in home-cooked meals and encouraging loved ones who may be experiencing loss of taste or smell to eat, Dr. Steinberg said.

“We’ve seen with the return of families and loved ones visiting to some extent has alleviated some people’s symptoms, especially psychological ones,” he said.

Dr. Tosato said he and his colleagues start with an individualized, multidisciplinary assessment to determine what types of care may help. He noted that physicians might recommend medications or rehabilitative therapies depending on the patient’s needs.

“A personalized approach is key,” Dr. Tosato said. His study also found that the proportion of older patients experiencing symptoms declined over time – a glimmer of hope that many will recover. 

Dr. Cohen emphasized the need for a multimodal rehabilitation, an evidence-based approach used to care for patients who survived hospitalization with severe COVID-19 – a group that has substantially higher rates of persistent symptoms. This approach includes cognitive rehabilitation, physical therapy, occupational therapy, and a graded exercise program.

Dr. Han and colleagues are studying potential therapies such as cognitive rehabilitation in adults who’ve experienced delirium. But until evidence-based treatments are available, they stress the role of support for patients with cognitive decline and their families.   

“A lot of the work we do is teach patients and their families to compensate for newly acquired cognitive deficits from any illness, including COVID-19,” Dr. Han said.

Ms. Salant said she has experienced some improvement in her energy since her pulmonologist recommended a new inhaler based on her symptoms. Her sense of smell and taste, lost to the infection, returned after she received her first dose of a vaccine against COVID-19. She takes comfort in participating in Survivor Corps, a group of more than 170,000 COVID-19 survivors and their families who advocate for more scientific research on the disease.

She also expressed gratitude for the support she receives from her primary care physician, who she said has taken the time to learn more about the symptoms of long COVID, listens to her, and respects what she has to say.

“I have hope that I will keep getting better by baby steps,” Ms. Salant said. 

Dr. Tosato, Dr. Steinberg, and Dr. Han have disclosed no relevant financial relationships.

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

Even mundane tasks such as making a meal can be exhausting for Louise Salant.

“I’m totally wiped out,” said the 71-year-old former private music instructor with asthma who lives in New York City and has been coping with debilitating symptoms of fatigue, shortness of breath, and gastrointestinal symptoms since recovering from a severe bout of COVID-19 2 years ago. “I just don’t have the energy.”

Ms. Salant is not alone. Many older people who contract COVID-19 experience prolonged symptoms of the disease. An analysis of Medicare Advantage claims data published in the BMJ found that about one-third of roughly 87,000 adults aged 65 in the database with a COVID-19 diagnosis sought care for persistent or new symptoms 21 or more days later.

That figure is about twice the rate of persistent COVID-19 related symptoms seen in a cohort of adults younger than age 65 with commercial insurance analyzed by the same group of researchers in a separate BMJ study. Compared with a 2020 comparator group of patients in this age cohort, these patients had a greater likelihood of respiratory failure, fatigue, hypertension, memory problems, kidney injury, mental health conditions, hypercoagulability, and cardiac rhythm disorders. When they compared post–COVID-19 symptoms to lasting symptoms of another serious viral disease – influenza – the researchers found that only respiratory failure, dementia, and post-viral fatigue were more common in the COVID-19 group.

“It became clear early in the pandemic that there is going to be a second pandemic related to all of the complications that we’ve seen related to COVID-19 infections,” said Ken Cohen, MD, executive director of translational research and national senior medical director for Optum Labs in Minnetonka, Minn., who coauthored the BMJ studies.

The results are among a growing body of evidence suggesting that older adults are at high risk of persistent post-COVID-19 symptoms.

Researchers in Rome, for example, found that 83% of 165 patients aged 65 or older who had been hospitalized for COVID-19 reported at least one lasting symptom – problems like fatigue, shortness of breath, joint pain, and coughing – in the months after hospitalization. One-third of those had two symptoms, and 46% had three or more.

A similar study in Norway found that two-thirds of patients aged 60 or older reported reduced health-related quality of life during follow-up visits 6 months after hospitalization for COVID-19. The most-reported impairments among those patients were the inability to perform the tasks of daily life, reduced mobility, and increased pain and discomfort.
 

Cognitive concerns

Mounting evidence indicates that COVID-19 may contribute to chronic cognitive impairment in older adults. A multisite U.S. study found that 28% of 817 adults presenting to emergency departments with COVID-19 had delirium and poorer outcomes. A Chinese case-control study that enrolled 1,438 individuals hospitalized in Wuhan for COVID-19, along with 438 of their uninfected spouses, found that 12% of COVID-19 survivors experienced cognitive impairment a year after discharge. Matteo Tosato, MD, PhD, head of the outpatient clinic for patients with long COVID symptoms at Gemelli Hospital in Rome, called those findings “very concerning.”

Jin Ho Han, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tenn., said cognitive impairment is common after an acute illness, particularly in frail or vulnerable patients.

“Hospitalization and the acute illness itself accelerate cognitive decline,” said Dr. Han, and previous evidence links delirium with worsening cognition. He and his colleagues are studying the potential role of delirium in longer-term cognitive decline in older patients after COVID-19.

Dr. Han emphasized the importance of preventing COVID-19-related delirium through vaccines and other strategies to reduce exposure of older patients to the virus. “Once you have cognitive decline, there are no interventions to reverse it,” he said.
 

Alarm bells for long-term care

Experts expressed concern that the situation might be even worse for people living in long-term care facilities. Many already need assistance with tasks of daily living and could be particularly vulnerable to lasting effects of COVID-19, said Karl Steinberg, MD, president of the Society for Post-Acute and Long-Term Care Medicine. He estimated that roughly half of his patients who have had COVID-19, regardless of the severity of their symptoms, have endured some degree of functional decline.

“It’s common for long-term care facility residents to experience functional and cognitive decline, even after seemingly minor things, like a cold or a trip to the hospital,” Dr. Steinberg, who has been a medical director of long-term care facilities in San Diego County for more than 2 decades, told this news organization. “It makes it a little harder to determine whether the declines we’ve been seeing post COVID in these residents are attributable to post COVID versus just an accelerated step in their overall expected decline.”

The pandemic may have contributed to worse outcomes for people in long-term care facilities in several ways: the disease itself, its effects on health care delivery, and necessary preventive measures to protect long-term care residents from exposure to the virus.

“During the many months where family visits were prohibited, we saw people – whether they had COVID-19 or not – suffer major clinical, functional, cognitive declines or severe psychological symptoms,” Dr. Steinberg said.

He emphasized the importance of preventive measures such as vaccines and boosters in patients in long-term care facilities. He said the benefit of preventing lasting symptoms is often a strong motivator for family caregivers of people with dementia to get them vaccinated or boosted.

“It’s clear that vaccination and booster reduce the incidence of post-COVID symptoms,” he said. Almost all studies have been in younger cohorts, but he expects the benefits would also apply to older patients.
 

Easing symptoms and offering support

As with long COVID generally, many questions remain about the causes of lasting symptoms of COVID-19 in older patients, and how best to treat them. Dr. Tosato, who led the study of long-COVID patients in Rome, is focusing on inflammation as a critical factor in the condition. He and colleagues across Europe hope to answer some of them by launching a multicenter study of lasting COVID-19 symptoms. 

In the meantime, Dr. Steinberg and Dr. Tosato said they are doing their best to evaluate and treat patients empirically.

“We pull from our armamentarium to treat system-specific symptoms,” Dr. Steinberg said. “We want to improve the quality of life and help each day be the best it can.”

Physicians in long-term care facilities might use medications such as antidepressants or nonpharmacologic approaches for patients experiencing depression symptoms. Families are also crucial in helping patients by bringing in home-cooked meals and encouraging loved ones who may be experiencing loss of taste or smell to eat, Dr. Steinberg said.

“We’ve seen with the return of families and loved ones visiting to some extent has alleviated some people’s symptoms, especially psychological ones,” he said.

Dr. Tosato said he and his colleagues start with an individualized, multidisciplinary assessment to determine what types of care may help. He noted that physicians might recommend medications or rehabilitative therapies depending on the patient’s needs.

“A personalized approach is key,” Dr. Tosato said. His study also found that the proportion of older patients experiencing symptoms declined over time – a glimmer of hope that many will recover. 

Dr. Cohen emphasized the need for a multimodal rehabilitation, an evidence-based approach used to care for patients who survived hospitalization with severe COVID-19 – a group that has substantially higher rates of persistent symptoms. This approach includes cognitive rehabilitation, physical therapy, occupational therapy, and a graded exercise program.

Dr. Han and colleagues are studying potential therapies such as cognitive rehabilitation in adults who’ve experienced delirium. But until evidence-based treatments are available, they stress the role of support for patients with cognitive decline and their families.   

“A lot of the work we do is teach patients and their families to compensate for newly acquired cognitive deficits from any illness, including COVID-19,” Dr. Han said.

Ms. Salant said she has experienced some improvement in her energy since her pulmonologist recommended a new inhaler based on her symptoms. Her sense of smell and taste, lost to the infection, returned after she received her first dose of a vaccine against COVID-19. She takes comfort in participating in Survivor Corps, a group of more than 170,000 COVID-19 survivors and their families who advocate for more scientific research on the disease.

She also expressed gratitude for the support she receives from her primary care physician, who she said has taken the time to learn more about the symptoms of long COVID, listens to her, and respects what she has to say.

“I have hope that I will keep getting better by baby steps,” Ms. Salant said. 

Dr. Tosato, Dr. Steinberg, and Dr. Han have disclosed no relevant financial relationships.

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

Even mundane tasks such as making a meal can be exhausting for Louise Salant.

“I’m totally wiped out,” said the 71-year-old former private music instructor with asthma who lives in New York City and has been coping with debilitating symptoms of fatigue, shortness of breath, and gastrointestinal symptoms since recovering from a severe bout of COVID-19 2 years ago. “I just don’t have the energy.”

Ms. Salant is not alone. Many older people who contract COVID-19 experience prolonged symptoms of the disease. An analysis of Medicare Advantage claims data published in the BMJ found that about one-third of roughly 87,000 adults aged 65 in the database with a COVID-19 diagnosis sought care for persistent or new symptoms 21 or more days later.

That figure is about twice the rate of persistent COVID-19 related symptoms seen in a cohort of adults younger than age 65 with commercial insurance analyzed by the same group of researchers in a separate BMJ study. Compared with a 2020 comparator group of patients in this age cohort, these patients had a greater likelihood of respiratory failure, fatigue, hypertension, memory problems, kidney injury, mental health conditions, hypercoagulability, and cardiac rhythm disorders. When they compared post–COVID-19 symptoms to lasting symptoms of another serious viral disease – influenza – the researchers found that only respiratory failure, dementia, and post-viral fatigue were more common in the COVID-19 group.

“It became clear early in the pandemic that there is going to be a second pandemic related to all of the complications that we’ve seen related to COVID-19 infections,” said Ken Cohen, MD, executive director of translational research and national senior medical director for Optum Labs in Minnetonka, Minn., who coauthored the BMJ studies.

The results are among a growing body of evidence suggesting that older adults are at high risk of persistent post-COVID-19 symptoms.

Researchers in Rome, for example, found that 83% of 165 patients aged 65 or older who had been hospitalized for COVID-19 reported at least one lasting symptom – problems like fatigue, shortness of breath, joint pain, and coughing – in the months after hospitalization. One-third of those had two symptoms, and 46% had three or more.

A similar study in Norway found that two-thirds of patients aged 60 or older reported reduced health-related quality of life during follow-up visits 6 months after hospitalization for COVID-19. The most-reported impairments among those patients were the inability to perform the tasks of daily life, reduced mobility, and increased pain and discomfort.
 

Cognitive concerns

Mounting evidence indicates that COVID-19 may contribute to chronic cognitive impairment in older adults. A multisite U.S. study found that 28% of 817 adults presenting to emergency departments with COVID-19 had delirium and poorer outcomes. A Chinese case-control study that enrolled 1,438 individuals hospitalized in Wuhan for COVID-19, along with 438 of their uninfected spouses, found that 12% of COVID-19 survivors experienced cognitive impairment a year after discharge. Matteo Tosato, MD, PhD, head of the outpatient clinic for patients with long COVID symptoms at Gemelli Hospital in Rome, called those findings “very concerning.”

Jin Ho Han, MD, associate professor of emergency medicine at Vanderbilt University, Nashville, Tenn., said cognitive impairment is common after an acute illness, particularly in frail or vulnerable patients.

“Hospitalization and the acute illness itself accelerate cognitive decline,” said Dr. Han, and previous evidence links delirium with worsening cognition. He and his colleagues are studying the potential role of delirium in longer-term cognitive decline in older patients after COVID-19.

Dr. Han emphasized the importance of preventing COVID-19-related delirium through vaccines and other strategies to reduce exposure of older patients to the virus. “Once you have cognitive decline, there are no interventions to reverse it,” he said.
 

Alarm bells for long-term care

Experts expressed concern that the situation might be even worse for people living in long-term care facilities. Many already need assistance with tasks of daily living and could be particularly vulnerable to lasting effects of COVID-19, said Karl Steinberg, MD, president of the Society for Post-Acute and Long-Term Care Medicine. He estimated that roughly half of his patients who have had COVID-19, regardless of the severity of their symptoms, have endured some degree of functional decline.

“It’s common for long-term care facility residents to experience functional and cognitive decline, even after seemingly minor things, like a cold or a trip to the hospital,” Dr. Steinberg, who has been a medical director of long-term care facilities in San Diego County for more than 2 decades, told this news organization. “It makes it a little harder to determine whether the declines we’ve been seeing post COVID in these residents are attributable to post COVID versus just an accelerated step in their overall expected decline.”

The pandemic may have contributed to worse outcomes for people in long-term care facilities in several ways: the disease itself, its effects on health care delivery, and necessary preventive measures to protect long-term care residents from exposure to the virus.

“During the many months where family visits were prohibited, we saw people – whether they had COVID-19 or not – suffer major clinical, functional, cognitive declines or severe psychological symptoms,” Dr. Steinberg said.

He emphasized the importance of preventive measures such as vaccines and boosters in patients in long-term care facilities. He said the benefit of preventing lasting symptoms is often a strong motivator for family caregivers of people with dementia to get them vaccinated or boosted.

“It’s clear that vaccination and booster reduce the incidence of post-COVID symptoms,” he said. Almost all studies have been in younger cohorts, but he expects the benefits would also apply to older patients.
 

Easing symptoms and offering support

As with long COVID generally, many questions remain about the causes of lasting symptoms of COVID-19 in older patients, and how best to treat them. Dr. Tosato, who led the study of long-COVID patients in Rome, is focusing on inflammation as a critical factor in the condition. He and colleagues across Europe hope to answer some of them by launching a multicenter study of lasting COVID-19 symptoms. 

In the meantime, Dr. Steinberg and Dr. Tosato said they are doing their best to evaluate and treat patients empirically.

“We pull from our armamentarium to treat system-specific symptoms,” Dr. Steinberg said. “We want to improve the quality of life and help each day be the best it can.”

Physicians in long-term care facilities might use medications such as antidepressants or nonpharmacologic approaches for patients experiencing depression symptoms. Families are also crucial in helping patients by bringing in home-cooked meals and encouraging loved ones who may be experiencing loss of taste or smell to eat, Dr. Steinberg said.

“We’ve seen with the return of families and loved ones visiting to some extent has alleviated some people’s symptoms, especially psychological ones,” he said.

Dr. Tosato said he and his colleagues start with an individualized, multidisciplinary assessment to determine what types of care may help. He noted that physicians might recommend medications or rehabilitative therapies depending on the patient’s needs.

“A personalized approach is key,” Dr. Tosato said. His study also found that the proportion of older patients experiencing symptoms declined over time – a glimmer of hope that many will recover. 

Dr. Cohen emphasized the need for a multimodal rehabilitation, an evidence-based approach used to care for patients who survived hospitalization with severe COVID-19 – a group that has substantially higher rates of persistent symptoms. This approach includes cognitive rehabilitation, physical therapy, occupational therapy, and a graded exercise program.

Dr. Han and colleagues are studying potential therapies such as cognitive rehabilitation in adults who’ve experienced delirium. But until evidence-based treatments are available, they stress the role of support for patients with cognitive decline and their families.   

“A lot of the work we do is teach patients and their families to compensate for newly acquired cognitive deficits from any illness, including COVID-19,” Dr. Han said.

Ms. Salant said she has experienced some improvement in her energy since her pulmonologist recommended a new inhaler based on her symptoms. Her sense of smell and taste, lost to the infection, returned after she received her first dose of a vaccine against COVID-19. She takes comfort in participating in Survivor Corps, a group of more than 170,000 COVID-19 survivors and their families who advocate for more scientific research on the disease.

She also expressed gratitude for the support she receives from her primary care physician, who she said has taken the time to learn more about the symptoms of long COVID, listens to her, and respects what she has to say.

“I have hope that I will keep getting better by baby steps,” Ms. Salant said. 

Dr. Tosato, Dr. Steinberg, and Dr. Han have disclosed no relevant financial relationships.

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

About 30% of COVID-19 patients developed the condition known as long COVID, University of California, Los Angeles, researchers said in a study published in the Journal of General Internal Medicine.

The UCLA researchers studied 1,038 people enrolled in the UCLA COVID Ambulatory Program between April 2020 and February 2021 and found that 309 developed long COVID.

A long-COVID diagnosis came if a patient answering a questionnaire reported persistent symptoms 60-90 days after they were infected or hospitalized. The most persistent symptoms were fatigue (31%) and shortness of breath (15%) in hospitalized participants. Among outpatients, 16% reported losing sense of smell.

The study’s findings differ from earlier research. The University of California, Davis, for example, estimated that 10% of COVID-19 patients develop long-haul symptoms. A 2021 study from Penn State University found that more than half of worldwide COVID-19 patients would develop long COVID.

Part of the discrepancy can blamed on the fact there is no official, widely accepted definition of long COVID. The Centers for Disease Control and Prevention has said it means patients who experience “new, returning, or ongoing health problems 4 or more weeks after an initial infection” the coronavirus. The UCLA study, meanwhile, included patients still having symptoms 60-90 days after infection.

Still, the UCLA research team looked at demographics and clinical characteristics in an attempt to develop effective treatments.

People with a history of hospitalization, diabetes, and higher body mass index were most likely to develop long COVID, the researchers said. The kind of insurance the patients had also seemed to be a factor, though the researchers didn’t offer a reason why.

“Surprisingly, patients with commercial insurance had double the likelihood of developing [long COVID] compared to patients with Medicaid,” they wrote. “This association will be important to explore further to understand if insurance status in this group is representing unmeasured demographic factors or exposures.”

Older age and socioeconomic status were not associated with long COVID in the study – a surprise because those characteristics are often linked with severe illness and higher risk of death from COVID-19.

Weaknesses in the study included the subjective nature of how patients rated their symptoms and the limited number of symptoms evaluated.

“This study illustrates the need to follow diverse patient populations ... to understand the long COVID disease trajectory and evaluate how individual factors such as preexisting comorbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of long COVID symptoms,” said Sun Yoo, MD, health sciences assistant clinical professor at UCLA.

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

About 30% of COVID-19 patients developed the condition known as long COVID, University of California, Los Angeles, researchers said in a study published in the Journal of General Internal Medicine.

The UCLA researchers studied 1,038 people enrolled in the UCLA COVID Ambulatory Program between April 2020 and February 2021 and found that 309 developed long COVID.

A long-COVID diagnosis came if a patient answering a questionnaire reported persistent symptoms 60-90 days after they were infected or hospitalized. The most persistent symptoms were fatigue (31%) and shortness of breath (15%) in hospitalized participants. Among outpatients, 16% reported losing sense of smell.

The study’s findings differ from earlier research. The University of California, Davis, for example, estimated that 10% of COVID-19 patients develop long-haul symptoms. A 2021 study from Penn State University found that more than half of worldwide COVID-19 patients would develop long COVID.

Part of the discrepancy can blamed on the fact there is no official, widely accepted definition of long COVID. The Centers for Disease Control and Prevention has said it means patients who experience “new, returning, or ongoing health problems 4 or more weeks after an initial infection” the coronavirus. The UCLA study, meanwhile, included patients still having symptoms 60-90 days after infection.

Still, the UCLA research team looked at demographics and clinical characteristics in an attempt to develop effective treatments.

People with a history of hospitalization, diabetes, and higher body mass index were most likely to develop long COVID, the researchers said. The kind of insurance the patients had also seemed to be a factor, though the researchers didn’t offer a reason why.

“Surprisingly, patients with commercial insurance had double the likelihood of developing [long COVID] compared to patients with Medicaid,” they wrote. “This association will be important to explore further to understand if insurance status in this group is representing unmeasured demographic factors or exposures.”

Older age and socioeconomic status were not associated with long COVID in the study – a surprise because those characteristics are often linked with severe illness and higher risk of death from COVID-19.

Weaknesses in the study included the subjective nature of how patients rated their symptoms and the limited number of symptoms evaluated.

“This study illustrates the need to follow diverse patient populations ... to understand the long COVID disease trajectory and evaluate how individual factors such as preexisting comorbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of long COVID symptoms,” said Sun Yoo, MD, health sciences assistant clinical professor at UCLA.

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

About 30% of COVID-19 patients developed the condition known as long COVID, University of California, Los Angeles, researchers said in a study published in the Journal of General Internal Medicine.

The UCLA researchers studied 1,038 people enrolled in the UCLA COVID Ambulatory Program between April 2020 and February 2021 and found that 309 developed long COVID.

A long-COVID diagnosis came if a patient answering a questionnaire reported persistent symptoms 60-90 days after they were infected or hospitalized. The most persistent symptoms were fatigue (31%) and shortness of breath (15%) in hospitalized participants. Among outpatients, 16% reported losing sense of smell.

The study’s findings differ from earlier research. The University of California, Davis, for example, estimated that 10% of COVID-19 patients develop long-haul symptoms. A 2021 study from Penn State University found that more than half of worldwide COVID-19 patients would develop long COVID.

Part of the discrepancy can blamed on the fact there is no official, widely accepted definition of long COVID. The Centers for Disease Control and Prevention has said it means patients who experience “new, returning, or ongoing health problems 4 or more weeks after an initial infection” the coronavirus. The UCLA study, meanwhile, included patients still having symptoms 60-90 days after infection.

Still, the UCLA research team looked at demographics and clinical characteristics in an attempt to develop effective treatments.

People with a history of hospitalization, diabetes, and higher body mass index were most likely to develop long COVID, the researchers said. The kind of insurance the patients had also seemed to be a factor, though the researchers didn’t offer a reason why.

“Surprisingly, patients with commercial insurance had double the likelihood of developing [long COVID] compared to patients with Medicaid,” they wrote. “This association will be important to explore further to understand if insurance status in this group is representing unmeasured demographic factors or exposures.”

Older age and socioeconomic status were not associated with long COVID in the study – a surprise because those characteristics are often linked with severe illness and higher risk of death from COVID-19.

Weaknesses in the study included the subjective nature of how patients rated their symptoms and the limited number of symptoms evaluated.

“This study illustrates the need to follow diverse patient populations ... to understand the long COVID disease trajectory and evaluate how individual factors such as preexisting comorbidities, sociodemographic factors, vaccination status and virus variant type affect type and persistence of long COVID symptoms,” said Sun Yoo, MD, health sciences assistant clinical professor at UCLA.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Patients with COVID-19, especially those with an altered sense of smell, have significantly more axon and microvasculopathy damage in the brain’s olfactory tissue versus non-COVID patients. These new findings from a postmortem study may explain long-term loss of smell in some patients with the virus.

“The striking axonal pathology in some cases indicates that olfactory dysfunction in COVID-19 may be severe and permanent,” the investigators led by Cheng-Ying Ho, MD, PhD, associate professor, department of pathology, Johns Hopkins University School of Medicine, Baltimore, write.

“The results show the damage caused by COVID can extend beyond the nasal cavity and involve the brain,” Dr. Ho told this news organization.

The study was published online April 11 in JAMA Neurology.
 

A more thorough investigation

Patients infected with SARS-CoV-2, which causes COVID-19, present with a wide range of symptoms. In addition to respiratory illnesses, they may exhibit various nonrespiratory manifestations of COVID-19.

One of the most prevalent of these is olfactory dysfunction. Research shows such dysfunction, including anosmia (loss of smell), hyposmia (reduced sense of smell), and parosmia (smells that are distorted or unpleasant), affects 30%-60% of patients with COVID-19, said Dr. Ho.

However, these statistics come from research before the advent of the Omicron variant, which evidence suggests causes less smell loss in patients with COVID, she said.

Previous studies in this area mainly focused on the lining of the nasal cavity. “We wanted to go a step beyond to see how the olfactory bulb was affected by COVID infection,” said Dr. Ho.

The study included 23 deceased patients with confirmed COVID-19 ranging in age from 28 to 93 years at death (median 62 years, 60.9% men). It also included 14 controls who tested negative for COVID-19, ranging in age from 20 to 77 years (median 53.5 years, 50% men).

Researchers collected postmortem tissue from the brain, lung, and other organs and reviewed pertinent clinical information.

Most patients with COVID died of COVID pneumonia or related complications, although some died from a different cause. Some had an active COVID infection and others were “post infection, meaning they were in the recovery stage,” said Dr. Ho.

Six patients with COVID-19 and eight controls had significant brain pathology.

Compared with controls, those with COVID-19 showed significantly worse olfactory axonal damage. The mean axon pathology score (range 1-3 with 3 the worst) was 1.921 in patients with COVID-19 and 1.198 in controls (95% confidence interval, 0.444-1.002; P < .001).

The mean axon density in the lateral olfactory tract was significantly less in patients with COVID-19 than in controls (P = .002), indicating a 23% loss of olfactory axons in the COVID group.

Comparing COVID patients with and without reported loss of smell, researchers found those with an altered sense of smell had significantly more severe olfactory axon pathology.
 

Vascular damage

Patients with COVID also had worse vascular damage. The mean microvasculopathy score (range, 1-3) was 1.907 in patients with COVID-19 and 1.405 in controls (95% CI, 0.259-0.745; P < .001).

There was no evidence of the virus in the olfactory tissue of most patients, suggesting the olfactory pathology was likely caused by vascular damage, said Dr. Ho.

What’s unique about SARS-CoV-2 is that, although it’s a respiratory virus, it’s capable of infecting endothelial cells lining vessels.

“Other respiratory viruses only attack the airways and won’t attack vessels, but vascular damage has been seen in the heart and lung in COVID patients, and our study showed the same findings in the olfactory bulb,” Dr. Ho explained.

The researchers divided patients with COVID by infection severity: mild, moderate, severe, and critical. Interestingly, those with the most severe olfactory pathology were the ones with milder infections, said Dr. Ho.

She noted other studies have reported patients with mild infection are more likely to lose the sense of smell than those with severe infection, but she’s skeptical about this finding.

“Patients with severe COVID are usually hospitalized and intubated, so it’s hard to get them to tell you whether they’ve lost smell or not; they have other more important issues to deal with like respiratory failure,” said Dr. Ho.

Advanced age is associated with neuropathologic changes, such as tau deposits, so the researchers conducted an analysis factoring in age-related brain changes. They found a COVID-19 diagnosis remained associated with increased axonal pathology, reduced axonal density, and increased vascular pathology.

“This means that the COVID patients had more severe olfactory pathology not just because they had more tau pathology,” Dr. Ho added.
 

New guidance for patients

Commenting for this news organization, Davangere P. Devanand, MD, professor of psychiatry and neurology and director of geriatric psychiatry, Columbia University Irving Medical Center, New York, said the findings indicate the damage from COVID in the olfactory pathway may not be reversible as was previously thought.

“This has been suggested before as a possibility, but the autopsy findings in this case series indicate clearly that there may be permanent damage,” he said.

The results highlight the need to monitor patients with COVID for a smell deficit, said Dr. Devanand. 

“Assuring patients of a full recovery in smell and taste may not be sound advice, although recovery does occur in many patients,” he added.

He praised the study design, especially the blinding of raters, but noted a number of weaknesses, including the small sample size and the age and gender discrepancies between the groups.

Another possible limitation was inclusion of patients with Alzheimer’s and Lewy body pathology, said Dr. Devanand.

“These patients typically already have pathology in the olfactory pathways, which means we don’t know if it was COVID or the underlying brain pathology contributing to smell difficulties in these patients,” he said.

He noted that, unlike deceased COVID cases in the study, patients who survive COVID may not experience axonal and microvascular injury in olfactory neurons and pathways and their sense of smell may make a full return.

Dr. Devanand said he would have liked more detailed information on the clinical history and course of study participants and whether these factors affected the pathology findings.

The study was supported by grants from the National Institutes of Health.

Dr. Ho and Dr. Devanand have reported no relevant financial disclosures.

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

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

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

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

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

Approximately one in five patients who presented with headache during the acute phase of COVID-19 developed chronic daily headache, according to a study published in Cephalalgia. The greater the headache’s intensity during the acute phase, the greater the likelihood that it would persist.

The research, carried out by members of the Headache Study Group of the Spanish Society of Neurology, evaluated the evolution of headache in more than 900 Spanish patients. Because they found that headache intensity during the acute phase was associated with a more prolonged duration of headache, the team stressed the importance of promptly evaluating patients who have had COVID-19 and who then experience persistent headache.
 

Long-term evolution unknown

Headache is a common symptom of COVID-19, but its long-term evolution remains unknown. The objective of this study was to evaluate the long-term duration of headache in patients who presented with this symptom during the acute phase of the disease.

Recruitment for this multicenter study took place in March and April 2020. The 905 patients who were enrolled came from six level 3 hospitals in Spain. All completed 9 months of neurologic follow-up.

Their median age was 51 years, 66.5% were women, and more than half (52.7%) had a history of primary headache. About half of the patients required hospitalization (50.5%); the rest were treated as outpatients. The most common headache phenotype was holocranial (67.8%) of severe intensity (50.6%).
 

Persistent headache common

In the 96.6% cases for which data were available, the median duration of headache was 14 days. The headache persisted at 1 month in 31.1% of patients, at 2 months in 21.5%, at 3 months in 19%, at 6 months in 16.8%, and at 9 months in 16.0%.

“The median duration of COVID-19 headache is around 2 weeks,” David García Azorín, MD, PhD, a member of the Spanish Society of Neurology and one of the coauthors of the study, said in an interview. “However, almost 20% of patients experience it for longer than that. When still present at 2 months, the headache is more likely to follow a chronic daily pattern.” Dr. García Azorín is a neurologist and clinical researcher at the headache unit of the Hospital Clínico Universitario in Valladolid, Spain.

“So, if the headache isn’t letting up, it’s important to make the most of that window of opportunity and provide treatment in that period of 6-12 weeks,” he continued. “To do this, the best option is to carry out preventive treatment so that the patient will have a better chance of recovering.”

Study participants whose headache persisted at 9 months were older and were mostly women. They were less likely to have had pneumonia or to have experienced stabbing pain, photophobia, or phonophobia. They reported that the headache got worse when they engaged in physical activity but less frequently manifested as a throbbing headache.
 

Secondary tension headaches

On the other hand, Jaime Rodríguez Vico, MD, head of the headache unit at the Jiménez Díaz Foundation Hospital in Madrid, said in an interview that, according to his case studies, the most striking characteristics of post–COVID-19 headaches “in general are secondary, with similarities to tension headaches that patients are able to differentiate from other clinical types of headache. In patients with migraine, very often we see that we’re dealing with a trigger. In other words, more migraines – and more intense ones at that – are brought about.”

He added: “Generally, post–COVID-19 headache usually lasts 1-2 weeks, but we have cases of it lasting several months and even over a year with persistent daily headache. These more persistent cases are probably connected to another type of pathology that makes them more susceptible to becoming chronic, something that occurs in another type of primary headache known as new daily persistent headache.”
 

Primary headache exacerbation

Dr. García Azorín pointed out that it’s not uncommon that among people who already have primary headache, their condition worsens after they become infected with SARS-CoV-2. However, many people differentiate the headache associated with the infection from their usual headache because after becoming infected, their headache is predominantly frontal, oppressive, and chronic.

“Having a prior history of headache is one of the factors that can increase the likelihood that a headache experienced while suffering from COVID-19 will become chronic,” he noted.

This study also found that, more often than not, patients with persistent headache at 9 months had migraine-like pain.

As for headaches in these patients beyond 9 months, “based on our research, the evolution is quite variable,” said Dr. Rodríguez Vico. “Our unit’s numbers are skewed due to the high number of migraine cases that we follow, and therefore our high volume of migraine patients who’ve gotten worse. The same thing happens with COVID-19 vaccines. Migraine is a polygenic disorder with multiple variants and a pathophysiology that we are just beginning to describe. This is why one patient is completely different from another. It’s a real challenge.”

Infections are a common cause of acute and chronic headache. The persistence of a headache after an infection may be caused by the infection becoming chronic, as happens in some types of chronic meningitis, such as tuberculous meningitis. It may also be caused by the persistence of a certain response and activation of the immune system or to the uncovering or worsening of a primary headache coincident with the infection, added Dr. García Azorín.

“Likewise, there are other people who have a biological predisposition to headache as a multifactorial disorder and polygenic disorder, such that a particular stimulus – from trauma or an infection to alcohol consumption – can cause them to develop a headache very similar to a migraine,” he said.
 

Providing prognosis and treatment

Certain factors can give an idea of how long the headache might last. The study’s univariate analysis showed that age, female sex, headache intensity, pressure-like quality, the presence of photophobia/phonophobia, and worsening with physical activity were associated with headache of longer duration. But in the multivariate analysis, only headache intensity during the acute phase remained statistically significant (hazard ratio, 0.655; 95% confidence interval, 0.582-0.737; P < .001).

When asked whether they planned to continue the study, Dr. García Azorín commented, “The main questions that have arisen from this study have been, above all: ‘Why does this headache happen?’ and ‘How can it be treated or avoided?’ To answer them, we’re looking into pain: which factors could predispose a person to it and which changes may be associated with its presence.”

In addition, different treatments that may improve patient outcomes are being evaluated, because to date, treatment has been empirical and based on the predominant pain phenotype.

In any case, most doctors currently treat post–COVID-19 headache on the basis of how similar the symptoms are to those of other primary headaches. “Given the impact that headache has on patients’ quality of life, there’s a pressing need for controlled studies on possible treatments and their effectiveness,” noted Patricia Pozo Rosich, MD, PhD, one of the coauthors of the study.

“We at the Spanish Society of Neurology truly believe that if these patients were to have this symptom correctly addressed from the start, they could avoid many of the problems that arise in the situation becoming chronic,” she concluded.

Dr. García Azorín and Dr. Rodríguez Vico disclosed no relevant financial relationships.

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

The Biden administration has announced a massive federal effort to better understand, diagnose, and treat the crippling effects of long COVID.

The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.

“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”

The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.

The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.

The United States has delivered more than 500 million vaccine doses to 114 countries.

Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.

New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.

Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.

“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.

Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.

Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.

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

The Biden administration has announced a massive federal effort to better understand, diagnose, and treat the crippling effects of long COVID.

The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.

“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”

The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.

The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.

The United States has delivered more than 500 million vaccine doses to 114 countries.

Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.

New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.

Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.

“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.

Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.

Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.

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

The Biden administration has announced a massive federal effort to better understand, diagnose, and treat the crippling effects of long COVID.

The National Research Action Plan on Long COVID will gather experts from various agencies, including the Department of Defense and the Department of Veterans Affairs, to expand existing long-COVID clinics and broaden research on symptoms of the virus that persist long after infection.

“We’ll collaborate with academic, industry, state and local partners to better understand long COVID,” Health and Human Services Secretary Xavier Becerra said at a White House briefing April 5. “We need to work as aggressively as we can to make sure no American is left behind.”

The plan will build on the RECOVER Initiative, a $1.15 billion effort announced last year that will study long COVID.

The COVID-19 Response Team also announced that the United States will donate tens of millions of pediatric coronavirus vaccines to other countries. More than 20 countries have asked for the donations, the team said.

The United States has delivered more than 500 million vaccine doses to 114 countries.

Meanwhile, national COVID-19 numbers continue to fall. CDC Director Rochelle Walensky, MD, reported that average daily cases are down 4% this week to 25,000; hospitalizations have dropped 17% to 1,400 per day; and daily deaths are down to 570 a day, which is a decrease of about 17%.

New national estimates show that Omicron’s subvariant BA.2 now accounts for 72% of circulating variants nationally, she said.

Top infectious disease expert Anthony Fauci, MD, reported that recent data supports the need for a second booster among certain people 50 and older – a move authorized by the Food and Drug Administration and Centers for Disease Control and Prevention last week.

“The effectiveness of the first booster dose we know wanes over time, and growing evidence shows a second dose can restore vaccine effectiveness for certain populations,” he said.

Dr. Fauci reported findings from an Israeli study of more than 1 million people 60 and older, which showed that an additional booster dose after 4 months lowered the rate of infection by two times and lowered the rate of severe infection by more than four times.

Another study from Israeli scientists showed that out of half a million people 60 and older, a second booster after 4 months brought a 78% reduction in death, compared to those who received only the first boost.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

Patients with persistent cognitive impairment months after illness with mild COVID-19 have higher levels of inflammatory markers in their cerebrospinal fluid (CSF). Researchers found elevated levels of CSF immune activation and immunovascular markers in individuals with cognitive postacute sequelae of SARS-CoV-2 infection (PASC). Patients whose cognitive symptoms developed during the acute phase of COVID-19 had the highest levels of brain inflammation.

The findings add to a growing body of evidence that suggests the condition often referred to as “brain fog” has a neurologic basis, said lead author Joanna Hellmuth, MD, MHS, assistant professor of neurology at the University of California, San Francisco Weill Institute of Neurosciences and the UCSF Memory and Aging Center.

The findings will be presented at the 2022 annual meeting of the American Academy of Neurology.
 

Inflammatory response

There are no effective diagnostic tests or treatments for cognitive PASC, which prompted the investigators to study inflammation in patients with the condition. Initial findings were reported earlier in 2022, which showed abnormalities in the CSF in 77% of patients with cognitive impairment. Patients without cognitive impairments had normal CSF.

Extending that work in this new study, researchers studied patients from the Long-term Impact of Infection With Novel Coronavirus (LIINC) study with confirmed SARS-CoV-2 infection who were not hospitalized. They conducted 2-hour neurocognitive interviews and identified 23 people with new, persistent cognitive symptoms (cognitive PASC) and 10 with no cognitive symptoms who served as controls.

All participants underwent additional neurologic examination and neuropsychological testing, and half agreed to a lumbar puncture to allow researchers to collect CSF samples. The CSF was collected a median of 10.2 months after initial COVID symptoms began.

Participants with cognitive PASC had higher median levels of CSF acute phase reactants C-reactive protein (0.007 mg/L vs. 0.000 mg/L; P =.004) and serum amyloid A (0.001 mg/L vs. 0.000 mg/L; P = .001), compared with COVID controls.

The PASC group also had elevated levels of CSF immune activation markers interferon gamma–inducible protein (IP-10), interleukin-8, and immunovascular markers vascular endothelial growth factor-C and VEGFR-1, although the differences with the control group were not statistically significant.

The timing of the onset of cognitive problems was also associated with higher levels of immune activation and immunovascular markers. Patients with brain fog that developed during the acute phase of COVID-19 had higher levels of CSF VEGF-C, compared with patients whose cognitive symptoms developed more than a month after initial COVID symptoms (173 pg/mL vs. 99 pg/mL; P = .048) and COVID controls (79 pg/mL; P = .048).

Acute onset cognitive PASC participants had higher CSF levels of IP-10 (P = .030), IL-8 (P = .048), placental growth factor (P = .030) and intercellular adhesion molecule-1 (P = .045), compared with COVID controls.

Researchers believe these new findings could mean that intrathecal immune activation and endothelial activation/dysfunction may contribute to cognitive PASC and that the mechanisms involved may be different in patients with acute cognitive PASC versus those with delayed onset.

“Our data suggests that perhaps in these people with more acute cognitive changes they don’t have the return to homeostasis,” Dr. Hellmuth said, while patients with delayed onset cognitive PASC had levels more in line with COVID patients who had no cognitive issues.
 

Moving the needle forward

Commenting on the findings, William Schaffner, MD, professor of infectious diseases, Vanderbilt University Medical Center, Nashville, Tenn., said that, while the study doesn’t rule out a possible psychological basis for cognitive PASC, it adds more weight to the biological argument.

“When you have nonspecific symptoms for which specific tests are unavailable,” Dr. Schaffner explained, “there is a natural question that always comes up: Is this principally a biologically induced phenomenon or psychological? This moves the needle substantially in the direction of a biological phenomenon.”

Another important element to the study, Dr. Schaffner said, is that the patients involved had mild COVID.

“Not every patient with long COVID symptoms had been hospitalized with severe disease,” he said. “There are inflammatory phenomenon in various organ systems such that even if the inflammatory response in the lung was not severe enough to get you into the hospital, there were inflammatory responses in other organ systems that could persist once the acute infection resolved.”

Although the small size of the study is a limitation, Dr. Schaffner said that shouldn’t minimize the importance of these findings.

“That it’s small doesn’t diminish its value,” he said. “The next step forward might be to try to associate the markers more specifically with COVID. The more precise we can be, the more convincing the story will become.”

The study was funded by the National Institutes of Health. Dr. Hellmuth received grant support from the National Institutes of Health/National Institute of Mental Health supporting this work and personal fees for medical-legal consultation outside of the submitted work. Dr. Schaffner disclosed no relevant financial relationships.

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

DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.

The findings are from an online survey of more than 800 respondents.

“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.

“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.

The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
 

100% report symptoms

The study included 827 respondents (81% women) to an online survey who had contracted COVID.

Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.

Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.

Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.

Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.

The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).

More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.

A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).

Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).

Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.

“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.

Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.

Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
 

Poor understanding of COVID’s fallout

In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.

“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.

Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.

Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.

“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.

“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.

“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.

The authors and Dr. Weich have disclosed no relevant financial relationships.

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

DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.

The findings are from an online survey of more than 800 respondents.

“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.

“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.

The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
 

100% report symptoms

The study included 827 respondents (81% women) to an online survey who had contracted COVID.

Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.

Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.

Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.

Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.

The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).

More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.

A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).

Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).

Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.

“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.

Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.

Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
 

Poor understanding of COVID’s fallout

In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.

“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.

Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.

Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.

“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.

“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.

“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.

The authors and Dr. Weich have disclosed no relevant financial relationships.

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

DENVER – Neurocognitive and psychiatric symptoms of mental illness, including posttraumatic stress disorder, are alarmingly high among patients who have previously had COVID-19 – even among those who were not hospitalized with the virus, new research shows.

The findings are from an online survey of more than 800 respondents.

“Regardless of how long ago they had been infected with COVID-19, all respondents had persistent symptoms,” co-investigator Beth Patterson, MSc, adjunct clinical professor at McMaster University, MacAnxiety Research Centre, Hamilton, Ont., told this news organization.

“The take-home message for clinicians is to be aware that if you have patients who had COVID-19, it’s quite likely that they may also experience a psychiatric issue and that they may have reduced resilience and lower quality-of-life [issues],” Ms. Patterson said.

The survey results were presented here at the Anxiety and Depression Association of America (ADAA) Conference 2022.
 

100% report symptoms

The study included 827 respondents (81% women) to an online survey who had contracted COVID.

Using validated symptom severity scores, respondents were assessed for mental health and neurocognitive issues, as well as some physical and quality-of-life factors.

Remarkably, all participants (100%) reported having current, persistent symptoms of COVID. In addition, 88% (n = 729) reported persistent neurocognitive symptoms, even though only 15.5% reported they had been hospitalized for COVID.

Of those hospitalized, 28.9% were treated in the intensive care unit; 42.2% stayed in hospital for less than 1 week; and 13.3% remained hospitalized for at least 3 weeks.

Data were not available on how long it had been since the patients were diagnosed or hospitalized, but most participants (68%) said they had not returned to normal functioning since contracting COVID.

The most common persistent symptoms were fatigue (75.9%), brain fog (67.9%), difficulty concentrating (61%), and weakness (51.2%).

More than half of respondents reported neurocognitive symptoms, including poor memory (57.4%) and word-finding problems in processing information (46.9%). Only 11% reported no persistent neurocognitive symptoms.

A total of 41.7% of respondents reported anxiety using the Generalized Anxiety Disorder-7 (GAD-7) scale, and rates of depression were 61.4% as assessed with the Patient Health Questionnaire (PHQ-9).

Rates of probable posttraumatic stress disorder were 40.5% as assessed via the PTSD checklist (PCL-5).

Although it wasn’t possible to use diagnostic screens, the assessment scores suggest strikingly high rates of mental health disorders among the respondents, Ms. Patterson said.

“When we look at the mean scores on the validated scales, we see percentages of probable diagnoses that are staggeringly higher than you would find in the population,” she added.

Of note, about 44% of respondents reported having had mental health treatment in the past, and 33.7% were receiving current mental health treatment.

Although the study had no control group, the findings are consistent with larger studies that have had comparator groups, including research recently published in the BMJ.
 

Poor understanding of COVID’s fallout

In an editorial accompanying the BMJ study, Scott Weich, MD, Mental Health Research Unit, School of Health and Related Research, University of Sheffield, United Kingdom, emphasized the need to better understand the lingering mental health aspects of COVID-19 infection.

“Our attachment to syndromal phenotypes means that we have learned remarkably little about the causes of mental ill health – in this case psychopathology associated with a viral pandemic,” Dr. Weich writes.

Dr. Weich called for improved efforts to understanding long COVID, as well as the establishment of more effective responses to the mental health fallout from the pandemic.

Commenting on the current study, Dr. Weich elaborated on the challenges in disentangling the causes of mental health effects in illness.

“In terms of other viruses, etc., there is a long history of debate and pitched battles between those that attribute mental health effects to predominantly biological processes, [involving] immunological and other responses, and those who understand these responses are mediated by psychological and social processes,” he noted.

“The story of myalgic encephalomyelitis/chronic fatigue syndrome speaks volumes about these different positions, and how difficult it can be to find a middle ground,” he said.

“This has been going on for centuries and may never be fully resolved, at least until we have clearer and more definitive evidence of pathophysiology, though this seems incredibly elusive,” Dr. Weich said.

The authors and Dr. Weich have disclosed no relevant financial relationships.

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

Long COVID symptoms may differ depending on which SARS-CoV-2 variant is behind a person’s infection, a new study shows.

The data from Italy compared long COVID symptoms reported by patients infected with SARS-CoV-2 from March to December 2020 (when the original, or “Wuhan,” variant was dominant) with those reported by patients infected from January to April 2021 (B.1.1.7-, or Alpha variant-dominant). It showed a substantial change in the pattern of neurological and cognitive/emotional problems – the latter mostly seen with the Alpha variant.

Infectious disease specialist Michele Spinicci, MD, from the University of Florence and Careggi University Hospital, Italy, led the work. “Many of the symptoms reported in this study have been measured [before], but this is the first time they have been linked to different COVID-19 variants,” he told this news organization. “Findings in patients with long COVID were focused on neurological and psychological difficulties.”

However, he pointed out that much remains to be understood about long COVID in terms of symptoms, diagnosis, and treatment. 

“Long COVID is a huge area that involves many different fields of medicine, so there is not one single piece of advice to give on management. There’s lots to consider when evaluating a long COVID patient,” he said.

Results showed that when the Alpha variant was the dominant variant, the prevalence of myalgia (10%), dyspnea (42%), brain fog/mental confusion (17%), and anxiety/depression (13%) significantly increased relative to the wild-type (original, Wuhan) variant, while anosmia (2%), dysgeusia (4%), and impaired hearing (1%) were less common.

When the wild-type (original, Wuhan) variant was dominant, fatigue (37%), insomnia (16%), dysgeusia (11%), and impaired hearing (5%) were all more common than with the Alpha variant. Dyspnea (33%), brain fog (10%), myalgia (4%), and anxiety/depression (6%) were less common. 

Overall, 76% of the patients in the trial reported at least one persistent symptom, while the most common reported symptoms were dyspnea (37%) and chronic fatigue (36%), followed by insomnia (16%), visual disorders (13%), and brain fog (13%).

The findings come from an early-release abstract that will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, in a few weeks’ time.
 

‘The take-home point’  

Michael A. Horberg, MD, associate medical director, Kaiser Permanente – Mid-Atlantic Permanente Medical Group, Rockville, Maryland, has recently presented data on symptoms seen with long COVID in over 28,000 people, as reported by this news organization, at the Conference on Retroviruses and Opportunistic Infections 2022. These people were infected with the wild-type virus.

Commenting on the study by Dr. Spinicci, he said: “The issue is that as we go along the COVID lifespan from acute to long COVID, what prompts patients to seek medical attention may change. If symptoms are not severe or were not well publicized previously, patients may not see the need to seek care or evaluation. As such, it doesn’t surprise me to find these changes over time, independent of any potential biological activity of the virus or its consequences.”

Dr. Horberg noted that their own study results are consistent with those of Dr. Spinicci et al. from March to December 2020 (original, Wuhan variant). “To me, the take-home point is long COVID is real, and physicians need to be on the lookout for it. However, not all symptoms are due to long COVID, and we need to keep the time course of symptoms during evaluation of such patients.”

Also providing comment on the findings was Debby Bogaert, MD, chair of Pediatric Medicine, University of Edinburgh. Reflecting on whether the symptoms were due to long COVID or another underlying disease, she said: “The number of patients with ongoing symptoms is very high, therefore [it is] unlikely that all of this is re-emergence of underlying or previous health problems. The type of symptoms reported are also as reported by other cohorts, so not unexpected. And irrespective of the root cause, they require care.”

Dr. Bogaert also noted that the data reiterate that COVID-19 is a new disease, and that “new variants might show shifting clinical pictures, not only regarding severity and symptoms of acute disease, but possibly also regarding sequela,” and that this, “underlines the importance of ongoing surveillance of variants, and ongoing evaluation of the acute and long-term clinical picture accompanying these, to ensure we adapt our public health approaches, clinical treatment plans, and long-term follow-up when and where needed.”

Dr. Bogaert stressed that only by keeping track of the changes in symptoms both acute and long-term – by patients and doctors – would the best patient care be provided.

“Patients need to know so they can report these back to their doctors, and doctors need to know over time that the picture of sequela might shift, so sequela are recognized early, and these patients receive the appropriate follow-up treatment,” she said. These shifting patterns might also apply to community patients as well as those hospitalized with COVID-19.
 

Study details

The retrospective, observational study included 428 patients, 59% men, with a mean age of 64 years, who had been treated at the Careggi University Hospital’s post-COVID outpatient service between June 2020 and June 2021, when the original form of SARS-CoV-2, and later the Alpha variant, were circulating, with some overlap.

All patients had been hospitalized with COVID-19 and discharged 4-12 weeks prior to attending the outpatient post-COVID service. They were asked to complete a questionnaire on persistent symptoms at the median of 53 days after being discharged from the hospital. In addition, data on medical history, microbiological and clinical COVID-19 course, self-reported symptoms (at the point of the follow-up visit), and patient demographics were obtained from electronic medical records.
 

Newer variants being studied

Upon analysis of long COVID symptoms according to treatment given during the acute phase using multivariate analysis, increasing oxygen support (odds ratio, 1.4; 95% confidence interval, 1.1-1.8), use of immunosuppressant drugs (OR, 6.4; 95% CI, 1.5-28), and female sex (OR, 1.8; 95% CI, 1.1-2.9) were associated with a higher risk for long COVID symptoms, while patients with type 2 diabetes (OR, 0.4; 95% CI, 0.2-0.7) had a lower risk of developing long COVID symptoms.

When asked whether the increased anxiety and depression seen with the Alpha variant might be also linked to the fact that people are living through hard times, with lockdowns, economic difficulties, possible illness, and even fatalities among family and friends due to COVID, Dr. Spinicci pointed out that “it’s a preliminary study, and there are lots of factors that we didn’t explore. It’s difficult to arrive at definite conclusions about long COVID because so much remains unknown. There are lots of external and environmental factors in the general population that might contribute to these findings.”

Dr. Spinicci has continued to enroll patients from later periods of the pandemic, including patients who were infected with the Delta and Omicron variants of SARS-CoV-2.

“We’re interested in finding out if these other variants are also associated with different phenotypes of long COVID. This study is part of our follow-up program here in the hospital where lots of different specialties are following patients for 20 months,” he said.

Dr. Horberg noted that one criticism of this study is that it was unclear whether the researchers accounted for pre-existing conditions. “They note the co-morbidities in the table 1, but don’t say how they accounted for that in their analyses. We found a lot of what patients were calling ‘long COVID’ were exacerbations of co-morbidities but not a new condition.” 

Dr. Spinicci and his coauthors acknowledged that the study was observational. And, as such, it does not prove cause and effect, and they could not confirm which variant of the virus caused the infection in different patients, which may limit the conclusions that can be drawn.

“Future research should focus on the potential impacts of variants of concern and vaccination status on ongoing symptoms,” Spinicci said.

Early release of an abstract will be presented at the European Congress of Clinical Microbiology & Infectious Diseases (ECCMID) 2022, in Lisbon, Portugal, April 23-26, 2022. Abstract 02768.

Dr. Spinicci and Dr. Horberg have disclosed no relevant financial relationships. Dr. Bogaert declared that she is on the program committee of ECCMID; she has been a member of SIGN/NICE COVID-19 rapid guideline: managing the long-term effects of COVID-19; and she is involved in multiple ongoing COVID-related studies, both acute and long-term sequela (funding MRC, CSO, ZonMw).

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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

COVID-19 infection appears to significantly raise the risk for diabetes by about 40% at 1 year, indicate new data from a very large Veterans Administration population.

“If patients have a prior history of COVID-19, that’s a risk factor for diabetes and they should certainly be screened for diabetes,” study coauthor Ziyad Al-Aly, MD, a nephrologist and chief of research and development at VA St. Louis Health Care, told this news organization.

“It’s still premature to make guidelines. I think we have to process the data landscape to understand what this all really means, but it’s really, really clear that all these roads are pointing in one direction, that COVID-19 increases the risk of diabetes up to a year later. The risk is small but not negligible,” he said.

The database includes over 8 million people and 180,000 with a prior COVID-19 diagnosis. Significantly increased diabetes risks compared to those not infected ranging from 31% to more than double were found in an analysis of subgroups based on diabetes risk score, body mass index, age, race, prediabetes status, and deprivation level, even after adjustment for confounding factors.

There was a gradient of diabetes risk by COVID-19 severity – i.e., whether patients had not been hospitalized, had been hospitalized, or stayed in intensive care – but a significant excess diabetes burden was seen even among those with “mild” COVID-19. The diabetes risk was also elevated compared to both contemporary and historical controls.

The study was published March 21 in The Lancet Diabetes & Endocrinology, by Yan Xie, MPH, also of VA St Louis Health Care, along with Dr. Al-Aly.

The data align with those from another study just published from a nationwide German primary care database. That study was smaller and of shorter duration than the new VA study but consistent, said Dr. Al-Aly, a clinical epidemiologist at Washington University, St. Louis.

Millions more with new diabetes as late manifestation of COVID-19

“Millions of people in the U.S. have had COVID-19, so this is going to translate to literally millions more people with new-onset diabetes. Better to identify them early so they can be adequately treated,” Dr. Al-Aly said in an interview.

“The long-term implications of SARS-CoV-2 infection increasing diabetes risk are profound,” Venkat Narayan, MD, and Lisa R. Staimez, PhD, both of the Rollins School of Public Health and Emory Global Diabetes Research Center at Emory University, Atlanta, said in an accompanying editorial.

“With large and growing numbers of people worldwide infected with SARS-CoV-2 (434,154,739 cumulative cases by Feb. 28, 2022), any COVID-19-related increases in diabetes incidence could lead to unprecedented cases of diabetes worldwide – wreaking havoc on already over-stretched and under-resourced clinical and public health systems globally, with devastating tolls in terms of deaths and suffering,” they added.

Medscape Medical News contributor Eric Topol MD, of Scripps Research Institute, La Jolla, Calif., agrees. He said these new data “are most profound. The researchers found a 40% increase in diabetes that wasn’t present at 1 month after COVID-19 but at 1 year, it was. Some kind of late manifestation is happening here.”  

Dr. Al-Aly told this news organization that the mechanisms for the association are unknown and likely to be heterogeneous. Among the people who already had risk factors for type 2 diabetes, such as obesity or metabolic syndrome, SARS-CoV-2 could simply accelerate that process and “put them over the edge” to overt diabetes.

However, for those without diabetes risk factors, “COVID-19 with all the inflammation it provokes in the body could be leading to de novo disease.” (Diabetes status was ascertained by ICD-10 codes and only about 0.70% of the total were recorded as type 1 diabetes. But, since autoantibody testing wasn’t routinely conducted, it’s unknown how many of the cases may have been type 1 misclassified as type 2, Dr. Al-Aly acknowledged.)
 

Diabetes risk significantly increased after COVID-19 in all analyses

The analysis included 181,280 patients in the U.S. Department of Veterans Affairs health care database with a COVID-19 diagnosis who survived for at least 30 days afterward during March 2020 through Sept. 30, 2021, with 4,118,441 contemporary controls without COVID-19 seen during 2019, and a historical control group of 4,286,911 people seen at the VA in 2017. Average follow-up was about a year.

Compared with the contemporary controls, the COVID-19 group had an excess diabetes burden of 13.46 per 1,000 person-years with a hazard ratio of 1.40. They had an increased 12.35 per 1,000 person-year risk for incident use of glucose-lowering medications, with a hazard ratio of 1.85. Similar results were seen with the historical controls.

Subgroup analyses showed an increased risk for diabetes following COVID-19 infection by age (≤ 65 years and > 65 years), race (White and Black), sex (male and female), BMI categories (> 18.5 to ≤ 25 kg/m², > 25 to ≤ 30 kg/m², and > 30 kg/m²), and area deprivation index quartiles. The increased risk was also seen across diabetes risk score quartiles.

Notably, COVID-19 significantly elevated the diabetes risk by 59% even for the subgroup with BMI between 18 and 25 kg/m², and by 38% among those with the lowest diabetes risk score quartile.

The COVID-19 population included 162,096 who were not hospitalized, 15,078 hospitalized, and 4,106 admitted to intensive care. Here, the hazard ratios for diabetes compared to the contemporary controls were 1.25, 2.73, and 3.76, respectively, all significant.  

Dr. Al-Aly said that his group is now further analyzing the VA data for other outcomes including cardiovascular disease and kidney disease, as well as the now well-documented long COVID symptoms including fatigue, pain, and neurocognitive dysfunction.

They’re also investigating the impact of the COVID-19 vaccine to see whether the risks are mitigated in the case of breakthrough infections: “We’re doing a broad systematic assessment. The next paper will be more comprehensive.”

Dr. Narayan and Dr. Staimez wrote: “The potential connection between COVID-19 and diabetes highlights that infectious diseases (eg, SARS-CoV-2) and chronic diseases (eg, diabetes) cannot be viewed in siloes. When we emerge out of the pandemic, the much-neglected non-communicable diseases, such as type 2 diabetes, will continue their relentless trajectory, possibly in an accelerated manner, as the leading burdens of global health.” 

Dr. Al-Aly declared support from the U.S. Department of Veterans Affairs for the submitted work. He has received consultation fees from Gilead Sciences and funding (unrelated to this work) from Tonix Pharmaceuticals. He is a member of the board of directors for Veterans Research and Education Foundation of Saint Louis, associate editor for the Journal of the American Society of Nephrology, and a member of multiple editorial boards. Dr. Narayan and Dr. Staimez have received support from the National Institutes of Health.

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