Long COVID

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

Harvard Medical School’s Sharon K. Inouye, MD, MPH, is editor in chief of JAMA Internal Medicine and a leading voice in American gerontology. We asked her to choose five of the influential journal’s most impactful studies from 2023 and highlight important take-home messages for internists and their colleagues.
 

Q: One of the studies you chose suggests that the antiviral nirmatrelvir (Paxlovid) can ward off long COVID. Could you recap the findings?

A: Researchers followed a group of more than 280,000 Department of Veterans Affairs patients who were seen in 2022, had a positive COVID test, and had at least one risk factor for severe COVID. They focused on those who survived to 30 days after their COVID infection and compared those who received the drug within the first 5 days of a positive test with an equivalent control group.

They found that 13 long COVID symptoms were all significantly less common (relative risk = 0.74) in those who received nirmatrelvir. This was true no matter whether they’d ever had a COVID vaccination.
 

Q: How should this research affect clinical practice?

A: You can’t generalize from this to everyone because, of course, not everyone was included in this study. But it is highly suggestive that this drug is very effective for preventing long COVID.

Nirmatrelvir was touted as being able to shorten duration of illness and prevent hospitalization. But if you were low risk or you were already well into your COVID course, it wasn’t like rush, rush, rush to the doctor to get it.

This changes that equation because we know long COVID is such a huge issue. The vast majority of doctors who work with COVID patients and know this are now being more aggressive about prescribing it.
 

Q: What about patients whom the CDC considers to be at less risk — people with up-to-date vaccinations who are under 50 with mild-to-moderate COVID and no higher-risk medical conditions? Should they take nirmatrelvir?

A: The evidence is not 100% in yet. A study like this one needs to be repeated and include younger people without any risk factors to see if we see the same thing. So it’s a personal choice, and a personal calculus needs to be done. A lot of people are making that choice [to take the drug], and it can be a rational decision.

Q: You also chose a study that links high thyroid hormone levels to higher rates of dementia. What did it reveal?

A: This study looks at patients who had thyrotoxicosis — a thyroid level that’s too high — from hormone produced endogenously, and exogenously. Researchers tracked almost 66,000 patients aged 65 and older and found that thyrotoxicosis from all causes, whether it was endogenous or exogenous, was linked to an increased risk of dementia in a dose-response relationship (adjusted hazard ratio = 1.39).

Q: Is there a clinical take-home message here?

A: When we start patients on thyroid medication, they don’t always get reassessed on a regular basis. Given this finding, a TSH [thyroid-stimulating hormone] level is indicated during the annual wellness check that patients on Medicare can get every year.

Q: Is TSH measured as part of routine blood tests?

A: No it’s not. It has to be ordered. I think that’s why we’re seeing this problem to begin with — because it’s not something we all have awareness about. I wasn’t aware myself that mildly high levels of thyroid could increase the risk of cognitive impairment. Certainly, I’m going to be much more aware in my practice.

Q: You also picked a study about silicosis in workers who are exposed to dust when they make engineered stone countertops, also known as quartz countertops. What were the findings?

A: Silicosis is a very serious lung condition that develops from exposure to crystalline silica. Essentially, sand gets inhaled into the lungs. Workers can be exposed when they’re making engineered stone countertops, the most popular countertops now in the United States.

This study is based on statewide surveys from 2019 to 2022 that the California Department of Public Health does routinely. They gathered cases of silicosis and found 52 — all men with an average age of 45. All but one were Latino immigrants, and most either had no insurance or very poor insurance.
 

Q: The study found that “diagnosis was delayed in 58%, with 38% presenting with advanced disease (progressive massive fibrosis), and 19% died.” What does that tell you?

A: It’s a very serious condition. Once it gets to the advanced stage, it will just continue to progress, and the person will die. That’s why it’s so important to know that it’s absolutely preventable.

Q: Is there a message here for internists?

A: If you treat a lot of immigrants or work in an area where there are a lot of industrial workers, you’re going to want to have a very high suspicion about it. If you see an atypical pattern on the chest x-ray or via diffusion scoring, have a low threshold for getting a pulmonary function test.

Doctors need to be aware and diagnose this very quickly. When patients present, you can pull them out of that work environment or put mitigation systems into place.
 

Q: California regulators were expected to put emergency rules into place in late December to protect workers. Did this study play a role in focusing attention on the problem?

A: This article, along with a commentary and podcast that we put out, really helped with advocacy to improve health and safety for workers at stone-cutting and fabrication shops.

Q: You were impressed by another study about airborne dangers, this one linking air pollution to dementia. What did researchers discover?

A: [This analysis] of more than 27,000 people in the Health and Retirement Study, a respected and rich database, found that exposure to air pollution was associated with greater rates of dementia — an increase of about 8% a year. Exposure to agricultural emissions and wildfire smoke were most robustly associated with a greater risk of dementia.

Q: How are these findings important, especially in light of the unhealthy air spawned by recent wildfires in the United States and Canada?

A: Studies like this will make it even more compelling that we are better prepared for air quality issues.

I grew up in Los Angeles, where smog and pollution were very big issues. I was constantly hearing about various mitigation strategies that were going into place. But after I moved to the East Coast, I almost never heard about prevention.

Now, I’m hoping we can keep this topic in the national conversation.
 

Q: You also highlighted a systematic review of the use of restraints in the emergency department. Why did you choose this research?

A: At JAMA Internal Medicine, we’re really focused on ways we can address health disparities and raise awareness of potential unconscious bias.

This review looked at 10 studies that included more than 2.5 million patient encounters, including 24,000 incidents of physical restraint use. They found that the overall rate of use of restraints was low at below 1%.

But when they are used, Black patients were 1.3 times more likely to be restrained than White patients.
 

Q: What’s the message here?

A: This is an important start to recognizing these differences and then changing our behavior. Perhaps restraints don’t need to be used as often in light of evidence, for example, of increased rates of misdiagnosis of psychosis in the Black population.

Q: How should physicians change their approach to restraints?

A: Restraints are not to be used to control disruption — wild behavior or verbal outbursts. They’re for when someone is a danger to themselves or others.

Dr. Inouye has no conflicts of interest.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

BETHESDA, MD — New research into the mechanisms underlying myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID is aimed at identifying potential approaches to treatment of the two overlapping illnesses.

According to a new data brief from the National Center for Health Statistics, in 2021-2022, 1.3% of US adults had ME/CFS, a complex, multisystem illness characterized by activity-limiting fatigue, worsening of symptoms after exertion, unrefreshing sleep, and other symptoms.

A 2-day conference, Advancing ME/CFS Research: Identifying Targets for Potential Intervention and Learning from Long COVID, was held in December 12-13 on the main campus of the US National Institutes of Health (NIH) and was livestreamed. The last such meeting, also featuring results from NIH-funded research, was held in April 2019.

“Things have changed since 2019 ... The idea of this meeting is to try and identify pathways that will be treatable and druggable and really make an impact for patients based on the things that we’ve learned over the last number of years and including, fortunately or unfortunately, the huge number of people who are suffering from long COVID, where the symptoms overlap so much with those who have been suffering for a long time with ME/CFS,” said Conference Chair Joe Breen, PhD, of the National Institute of Allergy and Infectious Diseases.

As in 2019, the meeting was preceded by a day of research presentations from young investigators, some of whom also presented their findings at the main meeting. New this year were four “lived experience” speakers who described their physical, emotional, and financial struggles with ME/CFS or long COVID. Two of them presented virtually because they were too ill to travel.

Social worker and patient advocate Terri Wilder of Minneapolis, Minnesota, reported some feedback she received on social media after she asked people with ME/CFS about their priorities for the research and clinical communities.

Among the top responses were the need to recognize and study the phenomenon of “post-exertional malaise” and to stop recommending exercise for people with these illnesses, to accelerate research to find effective treatments, and to put an end to stigma around the condition. “People don’t believe us when we tell them we’re sick, people make fun of us, misperceptions persist,” Wilder said.

One person commented, “[Clinicians] shouldn’t be afraid to try off-label meds with us if needed. There may be some secondary effects, but they are better options than us taking our own lives because we can’t stand the suffering.”

Research areas covered at the conference included immunology, virology, metabolism, gene regulation, and neurology of both ME/CFS and long COVID, as well as the latest findings regarding the overlap between the two conditions.
 

Oxidative Stress in Both ME/CFS and Long COVID: A Role for Metformin?

Mark M. Davis, PhD, professor and director of the Institute for Immunity, Transplantation, and Infection at Stanford University, Palo Alto, California, summarized published data suggesting that oxidative stress is a shared characteristic of both ME/CFS and long COVID. Most cellular reactive oxygen species (ROS) are produced in the cell’s mitochondria, and T-cell activation is ROS-dependent.

Women in particular with ME/CFS show high ROS levels with consistent T-cell hyperproliferation, “which can be suppressed with specific drugs such as metformin. This raises the prospect of optimizing drug treatment and drug discovery with a simple in vitro assay of the effects on a patient’s lymphocytes,” Dr. Davis said. He also cited a study suggesting that metformin may help prevent long COVID.

Asked to comment on that, longtime ME/CFS researcher Anthony L. Komaroff, MD, of Harvard University, Cambridge, Massachusetts, cautioned that although metformin is used safely by millions of people with type 2 diabetes worldwide, it’s possible that some people with ME/CFS may be more likely to experience its known adverse effects such as lactic acidosis.

To repurpose metformin or any other already-marketed drugs for ME/CFS and/or long COVID, Dr. Komaroff said, “We should entertain treatment trials.” However, as he and many others lamented at the conference, funding for off-patent drugs often isn’t forthcoming.
 

Addressing the Microbiome, Innate Immunity

W. Ian Lipkin, MD, of Columbia University, New York, NY, was one of two speakers who discussed the role of disruptions in the microbiome and innate immunity in ME/CFS. He presented data suggesting that “dysregulation of the gut microbiome in ME/CFS may interfere with butyrate production, resulting in inflammation and porosity to bacteria and bacterial products that trigger innate immunity.”

Dr. Lipkin highlighted a “really intriguing” paper in which exogenous administration of interleukin 37 (IL-37), a naturally occurring inhibitor of inflammation, reversed the decrease in exercise performance observed during inflammation-induced fatigue and increased exercise performance, both in mice.

“Although we do not fully understand the pathophysiology of ME/CFS, it is not premature to consider randomized clinical trials of pro- and pre-biotics that address dysbiosis as well as drugs that modify innate immune responses such as poly (I:C) and IL-37,” Dr. Lipkin said.
 

Alleviating Endoplasmic Reticulum (ER) Stress: A Strategy to Increase Energy?

Paul M. Hwang, MD, PhD, from the Cardiovascular Branch of the National Heart, Lung, and Blood Institute, Bethesda, Maryland, described work that he and his colleagues recently published around a case of a 38-year-old woman with Li-Fraumeni syndrome, a genetic early-onset cancer, who also had extensive fatigue, exercise intolerance, and post-exertional malaise that began after she contracted mononucleosis as a teenager.

Testing revealed that her cells had increased expression of Wiskott-Aldrich Syndrome Protein Family Member 3 (WASF3), a “top candidate” gene found to be associated with ME/CFS in a bioinformatics study published more than a decade ago. Moreover, immunoblotting of deidentified skeletal muscle biopsy samples obtained from patients with postinfectious ME/CFS also revealed significantly increased WASF3 levels.

Hwang and colleagues showed in mice that ER stress–induced WASF3 protein localizes to mitochondria and disrupts respiratory supercomplex assembly, leading to decreased oxygen consumption and exercise endurance.

However, use of the investigational protein phosphatase 1 inhibitor salubrinal in the female patient’s cells inhibited the ER stress, which in turn decreased WASF3 expression and improved mitochondrial supercomplex formation and respiration, “suggesting a treatment strategy in ME/CFS,” Dr. Hwang said.
 

Neurovascular Dysregulation During Exercise: A Role for Pyridostigmine?

David M. Systrom, MD, a pulmonary and critical care medicine specialist at the Brigham and Women’s Hospital, Boston, Massachusetts, gave an update of his work investigating neurovascular dysregulation during exercise in both ME/CFS and long COVID using invasive cardiopulmonary testing.

In a 2021 publication, Dr. Systrom and his colleagues identified the mechanism of “preload failure,” or lower filling pressures of blood in the heart chambers because of insufficient vein constriction and reduced return of blood to the right side of the heart in people with ME/CFS, compared with healthy controls.

Subsequently, in a randomized trial of 45 patients with ME/CFS, Systrom and his colleagues published in November 2022, use of the cholinesterase inhibitor pyridostigmine, currently approved for treating myasthenia gravis and related conditions, improved peak Vo2 by increasing cardiac output and filling pressures.

Now, Dr. Systrom’s team is conducting a randomized trial comparing 60 mg pyridostigmine with or without low-dose naltrexone (LDN) vs placebo in 160 patients with ME/CFS for 3 months. Metabolomic, transcriptomic, proteomic, and other assessments will be conducted on urine and blood samples. Participants will also wear devices that measure steps, sleep, heart rate, and other metrics.

Komaroff cautioned that pyridostigmine, too, has potential adverse effects. “I’m not sure pyridostigmine is ready for prime time ... It’s a drug developed for a very different purpose ... Now will it hold up in a larger trial, and will there be any side effects that turn up in larger studies? It’s not unreasonable to study.”
 

Brain Inflammation: Measuring and Treating It

Hannah F. Bues, clinical research coordinator at Massachusetts General Hospital, Boston, presented data now in preprint (ie, not yet peer-reviewed) in which researchers used [11C]PBR28 PET neuroimaging, a marker of neuroinflammation, to compare 12 individuals with long COVID vs 43 healthy controls. They found significantly increased neuroinflammation in several different brain regions in the long COVID group compared with controls.

Samples of peripheral blood plasma also showed significant correlations between neuroinflammation and circulating analytes related to vascular dysfunction. This work is ongoing in both long COVID and pre-COVID ME/CFS populations, Bues said.

Jarred Younger, PhD, of the Neuroinflammation, Pain, and Fatigue Laboratory at the University of Alabama, Birmingham, also gave an update of his ongoing work demonstrating significant brain inflammation seen in neuroimaging of people with ME/CFS compared with healthy controls.

Dr. Younger has been investigating the use of LDN for pain in fibromyalgia. Anecdotally, there have been reports of fatigue reduction with LDN in ME/CFS.

Dr. Younger conducted a post hoc analysis of his previous trial of LDN for 12 weeks in 30 patients with fibromyalgia. Of those, 16 met older CFS criteria. There was a significant reduction in their fatigue severity, with P <.0001 from baseline and P < .009 compared with placebo. The P values were high because the data included daily symptom reports. The average fatigue reduction was 25%.

“It wasn’t a study designed for ME/CFS, but I think it’s compelling evidence and enough with the other types of data we have to say we need to do a proper clinical trial of low-dose naltrexone in ME/CFS now,” Dr. Younger said.
 

‘We Need to Do Something’ About the Underfunding

Another NIH-funded ME/CFS researcher, Maureen Hanson, PhD, of Cornell University, Ithaca, NY, noted that the NIH currently funds ME/CFS research at about $13 million compared with $1.15 billion for the Researching COVID to Enhance Recovery Initiative granted to NIH by Congress for “post-acute sequelae of SARS-CoV-2 (PASC)” in 2021 “because of the urgency of studying this. Most of us here are well aware of the underfunding of ME/CFS relative to the burden of illness,” she said.

Current 2024 funding for AIDS research is $3294 million. “There are 1.2 million individuals living with HIV in the United States, and there are over 3 million who are barely living with ME/CFS in the United States. We need to do something about this ... It’s certainly possible that future funding for PASC is now going to disappear,” Dr. Hanson cautioned.

Wilder, the patient advocate, reminded the audience that “There is a cohort of people with ME who got sick in the 1980s and 1990s in the prime of their life ... They have dreamed of a day when there would be a major announcement that a treatment has been discovered to take away the suffering of this disease ... They keep waiting and waiting, year after year, missing more and more of their lives with each passing day ... We’re all depending on you.”

Dr. Systrom has received funding from the Solve ME/CFS Initiative, Department of Defense, and Open Medicine Foundation. Dr. Younger’s work is funded by the NIH, Department of Defense, SolveME, the American Fibromyalgia Association, and ME Research UK. Dr. Lipkin and Dr. Hanson receive NIH funding. Dr. Komaroff has no disclosures.
 

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

The COVID-19 pandemic may no longer be a global public health emergency, but millions continue to struggle with the aftermath: Long COVID. New research and clinical anecdotes suggest that certain individuals are more likely to be afflicted by the condition, nearly 4 years after the virus emerged. 

People with a history of allergies, anxiety or depression, arthritis, and autoimmune diseases and women are among those who appear more vulnerable to developing long COVID, said doctors who specialize in treating the condition.

Many patients with long COVID struggle with debilitating fatigue, brain fog, and cognitive impairment. The condition is also characterized by a catalog of other symptoms that may be difficult to recognize as long COVID, experts said. That’s especially true when patients may not mention seemingly unrelated information, such as underlying health conditions that might make them more vulnerable. This makes screening for certain conditions and investigating every symptom especially important. 

The severity of a patient’s initial infection is not the only determining factor for developing long COVID, experts said.

“Don’t judge the person based on how sick they were initially,” said Mark Bayley, MD, medical director of the Toronto Rehabilitation Institute at University Health Network and a professor with the Temerty Faculty of Medicine at the University of Toronto. “You have to evaluate every symptom as best you can to make sure you’re not missing anything else.” 

Someone who only had a bad cough or felt really unwell for just a few days and recovered but started feeling rotten again later — “that’s the person that we are seeing for long COVID,” said Dr. Bayley. 

While patients who become severely sick and require hospitalization have a higher risk of developing long COVID, this group size is small compared with the much larger number of people infected overall. As a result, despite the lower risk, those who only become mild to moderately sick make up the vast majority of patients in long COVID clinics. 

A small Northwestern Medicine study found that 41% of patients with long COVID never tested positive for COVID-19 but were found to have antibodies that indicated exposure to the virus. 

Doctors treating patients with long COVID should consider several risk factors, specialists said. They include:

• A history of asthma, eczema, or allergies
• Signs of autonomic nervous system dysfunction
• Preexisting immune system issues
• Chronic infections
• Diabetes
• Being slightly overweight
• A preexisting history of anxiety or depression
• Joint hypermobility ( being “double-jointed” with pain and other symptoms)

Screening for Allergies

Alba Azola, MD, assistant professor of Physical Medicine and Rehabilitation at Johns Hopkins Medicine, said a history of asthma, allergies, and eczema and an onset of new food allergies may be an important factor in long COVID that doctors should consider when evaluating at-risk patients.

It is important to identify this subgroup of patients because they respond to antihistamines and mast cell stabilizers, which not only relieve their allergy symptoms but may also help improve overall fatigue and their tolerance for basic activities like standing, Dr. Azola said.

A recently published systemic review of prospective cohort studies on long COVID also found that patients with preexisting allergic conditions like asthma or rhinitis may be linked to a higher risk of developing long COVID. The authors cautioned, however, that the evidence for the link is uncertain and more rigorous research is needed.

“It stands to reason that if your immune system tends to be a bit hyperactive that triggering it with a virus will make it worse,” said Dr. Bayley.


 

Signs of Dysautonomia, Joint Hypermobility

Patients should also be screened for signs and symptoms of dysautonomia, or autonomic nervous system disorder, such as postural orthostatic tachycardia syndrome (POTS) or another type of autonomic dysfunction, doctors said.

“There’s a whole list because the autonomic nervous system involves every part of your body, every system,” Dr. Azola said.

Issues with standing, vision, digestion, urination, and bowel movement, for example, appear to be multisystemic problems but may all be linked to autonomic dysfunction, she explained.

Patients who have POTS usually experience a worsening of symptoms after COVID infection, Dr. Azola said, adding that some patients may have even assumed their pre-COVID symptoms of POTS were normal. 

She also screens for joint hypermobility or hypermobile Ehlers-Danlos syndrome, which affects connective tissue. Research has long shown a relationship between autonomic dysfunction, mast cell activation syndrome (repeated severe allergy symptoms that affect multiple systems), and the presence of hypermobility, Dr. Azola said. She added that gentle physical therapy can be helpful for patients with hypermobility issues.

Previous studies before and during the pandemic have also found that a substantial subset of patients with myalgic encephalomyelitis/chronic fatigue syndrome, which shares many similarities with long COVID, also have connective tissue/hypermobility disorders.
 

Depression, Anxiety, and Female Patients

People with a preexisting history of anxiety or depression also appear to be at a higher risk for long COVID, Dr. Bayley said, noting that patients with these conditions appear more vulnerable to brain fog and other difficulties brought on by COVID infection. Earlier research found biochemical evidence of brain inflammation that correlates with symptoms of anxiety in patients with long COVID.

“We know that depression is related to neurotransmitters like adrenaline and serotonin,” Dr. Bayley said. “The chronic inflammation that’s associated with COVID — this will make people feel more depressed because they’re not getting the neurotransmitters in their brain releasing at the right times.”

It may also put patients at a risk for anxiety due to fears of post-exertional malaise (PEM), where symptoms worsen after even very minor physical or mental exertion and can last days or weeks.

“You can see how that leads to a bit of a vicious cycle,” said Dr. Bayley, explaining that the cycle of fear and avoidance makes patients less active and deconditioned. But he added that learning to manage their activity can actually help mitigate PEM due to the anti-inflammatory effects of exercise, its positive impact on mood, and benefits to the immune and cardiovascular systems. 

Meanwhile, a number of epidemiologic studies have found a higher prevalence of long COVID among women. Perimenopausal and menopausal women in particular appeared more prone, and at least one study reported that women under 50 years were five times more likely to develop post-COVID symptoms than men.

A recent small UK study that focused on COVID-19 hospitalizations found that women who had lower levels of inflammatory biomarkers at admission were more likely to experience certain long-term symptoms like muscle ache, low mood and anxiety, adding to earlier research linking female patients, long COVID, and neuropsychiatric symptoms. 


 

History of Immune Dysfunction, Diabetes, Elevated Body Mass Index (BMI)

Immune dysfunction, a history of recurrent infections, or chronic sinus infections are also common among patients under Dr. Azola and her team’s care. Those who have arthritis or other autoimmune diseases such as lupus also appear more vulnerable, Dr. Bayley said, along with patients who have diabetes or a little overweight.

Recent research out of the University of Queensland found that being overweight can negatively affect the body’s immune response to the SARS-CoV-2 virus. Blood samples collected 13 months after infection, for example, found that individuals with a higher BMI had lower antibody activity and a reduced percentage of relevant B cells that help build antibodies to fight the virus. Being overweight did not affect the antibody response to the COVID-19 vaccines, however, giving further support for vaccination over infection-induced immunity as an important protective factor, researchers said.
 

Narrowing the Information Gap

The latest Centers for Centers for Disease Control and Prevention’s Household Pulse Survey estimates that 14% of all American adults have had long COVID at some point, with more than 5% of the entire adult population currently experiencing long COVID. With millions of Americans affected, experts and advocates highlight the importance of bridging the knowledge gap with primary care doctors. 

Long COVID specialists said understanding these connections helps guide treatment plans and manage symptoms, such as finding the right medications, improving tolerance, optimizing sleep, applying cognitive strategies for brain fog, dietary changes, respiratory exercises to help with shortness of breath, and finding the fine line between what causes PEM and what doesn’t. 

“Whenever you see a disease like this one, you always have to ask yourself, is there an alternative way of looking at this that might explain what we’re seeing?” said Dr. Bayley. “It remains to be said that all bets are still open and that we need to continue to be very broad thinking about this.”

A version of this article appeared on Medscape.com.

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

A treatment used to treat acute COVID-19 infection has also been found to be effective against long COVID, a new small study has found. The research, which assessed the benefits of monoclonal antibodies, suggests relief may finally be ahead for millions of Americans with long COVID for whom treatment has remained elusive.

The study, published in the American Journal of Emergency Medicine, found three Florida patients with long COVID made complete — and sudden — recoveries after they were given the monoclonal antibody cocktail casirivimab/imdevimab (Regeneron).

“We were struck by how rapid and complete the remissions were,” said study coauthor Paul Pepe, MD, MPH, a professor of management, policy, and community health at the School of Public Health at the University of Texas Health Sciences Center. “We found that no matter how long the patients were sick for — whether it was 5, 8, or 18 months — within 5 days, they appeared to be completely cured.”

All three patients had been initially infected with COVID-19 early in the pandemic, in 2020 or the first half of 2021. They were given Regeneron either after a reinfection or exposure to COVID-19, as a preventative, at state-run COVID clinics in Florida.

“In each case, the infusions were given to help prevent their long COVID from worsening,” said Dr. Pepe.

The researchers collected medical histories for all three patients, asking about symptoms such as physical fatigue, exercise intolerance, chest pain, heart palpitations, shortness of breath, cognitive fatigue, and memory problems. They asked patients to rate symptoms pre-COVID (baseline), during the long COVID phase, post-vaccine, and finally a week after their monoclonal antibody treatment. They also interviewed family members.

They found that across the board, symptoms improved significantly and often completely vanished. Their loved ones corroborated these reports as well.

One of the patients, a 63-year-old Floridian woman, came down with a mild case of COVID-19 at the start of the pandemic in March 2020 that lasted about 2 weeks. But several weeks later, she developed extreme, debilitating fatigue, along with chest pain and shortness of breath.

“I was chasing my 6-pound Yorkie one day after she got loose, and I was struck with such intense chest pain I fell down,” the woman, asking not to be identified, said in an interview.

Her symptoms progressed to the point where she no longer felt safe babysitting her grandchildren or driving to the grocery store.

“My short-term memory was completely gone. I couldn’t even read more than a paragraph at a time,” she said.

When she was exposed to COVID-19 in October 2021, her doctor suggested Regeneron as a preventative. She agreed to it.

“I was terrified that a second round would leave me permanently disabled and stuck in bed for the rest of my life,” she said.

About 4 days after her monoclonal antibody treatment, she noticed that some of the brain fog that had persisted after COVID was lifting.

“By day 5, it felt almost like a heavy-weighted blanket had been lifted off of me,” she recalled. “I was able to take my dog for a walk and go to the grocery store. It felt like I had gone from 0 to 100. As quickly as I went downhill, I quickly went back up.”

Reasons for Recovery

Researchers have come up with a few theories about why monoclonal antibodies may help treat long COVID, said study coauthor Aileen Marty, MD, professor of translational medicine at the Herbert Wertheim College of Medicine at Florida International University. Among them:

• It stimulates the body to fight off any residual virus. “We suspect that many of these patients simply have levels of virus that are so low they can’t be picked up by conventional testing,” said Dr. Marty. “The virus lingers in their body and causes long COVID symptoms. The monoclonal antibodies can zero in on them and knock them out.” This may also help explain why some patients with long COVID reported a temporary improvement of symptoms after their COVID-19 vaccination.
• It combats dysfunctional antibodies. Another theory is that people with long COVID have symptoms “not because of residual virus but because of junky antibodies,” said Dr. Marty. These antibodies go into overdrive and attack your own cells, which is what causes long COVID symptoms. “This may be why monoclonal antibodies work because they displace the dysfunctional antibodies that are attached to a patient’s cells,” she explained.
• Reactivation of other viruses. Long COVID is very similar to chronic fatigue syndrome, which is often thought to be triggered by reactivation of viruses like the Epstein-Barr virus, noted coauthor Nancy Klimas, MD, director of the Institute for Neuro-Immune Medicine at Nova Southeastern University in Fort Lauderdale. “It may not explain all of the cases of long COVID, but it could make up a subgroup,” she said. It’s thought that the monoclonal antibodies may perhaps neutralize this reactivation.

Where Research Is Headed

While Regeneron worked well in all three patients, it may be because they developed long COVID from either the initial virus or from early variants like Alpha, Beta, and Delta, said Dr. Pepe. As a result, it’s unclear whether this treatment would work for patients who developed long COVID from newer strains like Omicron.

“What concerns me is I believe there may be many people walking around with mild long COVID from these strains who don’t realize it,” he said. “They may assume that if they have difficulty walking upstairs, or forget why they went into another room, that it’s age related.”

The next step, the researchers said, is to create a registry of volunteer patients with severe long COVID. Dr. Klimas plans to enroll 20 volunteers who were infected before September 2022 to see how they respond to another monoclonal antibody initially used to treat COVID-19, bebtelovimab. (Like Regeneron, bebtelovimab is no longer approved for use against COVID-19 by the US Food and Drug Administration because it is no longer effective against variants of the virus circulating today.)

As for patients who developed long COVID after September 2022, research is ongoing to see if they respond to other monoclonal antibodies that are in development. One such study is currently enrolling participants at the University of California San Francisco. The center is recruiting 30 patients with long COVID to try a monoclonal antibody developed by Aerium Therapeutics.

“They created an investigational monoclonal antibody to treat acute COVID, but it proved less effective against variants that emerged in late 2022,” said lead investigator Michael Peluso, MD, an assistant professor of medicine in the Division of HIV, Infectious Diseases, and Global Medicine at the University of California San Francisco. The hope is it may still work to fight long COVID among patients infected with those variants.

In the meantime, the three patients with long COVID who responded to Regeneron have resumed life as they knew it pre-COVID. Although two subsequently became infected with COVID again, they recovered quickly and did not see symptoms return, something which, for them, seems nothing short of miraculous.

“I had prepared myself to be disabled for life,” said one of the patients, a 46-year-old Floridian woman who developed long COVID after an infection in January 2021. “I had crippling fatigue and dizziness so intense I felt like I was walking on a trampoline. My brain fog was so pronounced I had to write everything down constantly. Otherwise, I’d forget.”

When she became infected with COVID again in September 2021, “I thought I was going to die because I had no idea how I could possibly get worse,” she recalled. Her doctors recommended Regeneron infusion treatment. Forty-eight hours later, her symptoms improved significantly.

“I was able to go out to a cocktail party and dinner for the first time in months,” she said. “I would not have been able to do either of those things a week before.”

It’s also profoundly affected her husband, who had had to take over running the household and raising their five children, aged 11-22 years, for months.

“I can’t tell you how many school events and sports games I missed because I physically didn’t have the strength to get to them,” she noted. “To this day, my husband gets upset whenever we talk about that time. Long COVID literally took over all of our lives. It was devastating to me, but it’s just as devastating for loved ones, too. My family is just grateful to have me back.”

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

Though many people remain on the fence about getting the latest COVID vaccine booster, new research suggests a strong argument for getting the shot this winter: It sharply reduces the risk for COVID. 

Researchers found that getting vaccinated led to a 69% reduction in long-COVID risk among adults who received three vaccines before being infected. The risk reduction was 37% for those who received two doses. Experts say the research provides a strong argument for getting the vaccine, noting that about 10% of people infected with COVID go on to have long COVID, which can be debilitating for one quarter of those with long-lasting symptoms.

The data come from a systematic literature review and meta-analysis published in October in Antimicrobial Stewardship & Epidemiology. Researchers examined 32 studies published between December 2019 and June 2023, involving 775,931 adults. Twenty-four studies, encompassing 620,221 individuals, were included in the meta-analysis. 

“The body of evidence from all these different studies converge on one single reality — that vaccines reduce the risk of long COVID, and people who keep up to date on their vaccinations also fared better than people who got it once or twice and didn’t follow up,” said Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University in St Louis. 

Researchers have reported similar results for children. The National Institutes of Health RECOVER Initiative team found that vaccines are up to 42% effective in preventing long COVID in children, said Dr. Carlos Oliveira, MD, a pediatric infectious diseases specialist and Yale researcher who contributed to the study, which is in preprint. 

Vaccines also protect children from multisystem inflammatory syndrome, a condition that can happen after COVID, as well as protect against other COVID-related problems, such as missed school days, Oliveira said. “Even if the vaccine doesn’t completely stop long COVID, it’s still good for kids to get vaccinated for all these other reasons.” 

However, uptake for the latest boosters has been slow: the Centers for Disease Control and Prevention reported that by mid-November, less than 16% of people aged 18 years or older had received a shot. For children, the number was closer to 6%. A recent Kaiser Family Foundation survey found that booster rates for adults are similar to what it was 1 year ago. 

The survey results suggest that people are no longer as worried about COVID, which is why there is less concerned about keeping up with boosters. Though the current mutation of the virus is not as debilitating as its predecessors, long COVID continues to be a problem: as of January 2023, 28% of people who had contracted the virus had experienced long-COVID symptoms. And though the mechanisms are still not fully understood, and researchers have yet to agree on a definition of long COVID, they are certain about this much: The best way to avoid it is to avoid getting infected to begin with. 

The lack of a diagnostic test for long COVID and the fact that the symptoms mimic those of other diseases lead to inconsistency that can make studies hard to replicate. In the papers reviewed for the Antimicrobial Stewardship & Epidemiology study, long COVID was defined as having symptoms lasting from more than 4 weeks to more than 6 months. Alexandre Marra, MD, the lead author and a researcher at the Hospital Israelita Albert Einstein, in São Paulo, Brazil, and at the University of Iowa, said that a clear standard definition is needed to better understand the actual prevalence and evaluate vaccine effectiveness. 

Al-Aly noted that there is a logical explanation for one finding in the paper: The percentage of individuals who had COVID and reported that long-COVID symptoms declined from 19% in June 2022 to 11% in January 2023. 

Because a pandemic is a dynamic event, constantly producing different variants with different phenotypes, the prevalence of disease is naturally going to be affected. “People who got infected early in the pandemic may have a different long COVID profile and long COVID risk than people who got infected in the second or third year of the pandemic,” Al-Aly said. 

Most of the studies reported data from before the Omicron-variant era. Only eight reported data during that era. Omicron was not as lethal as previous variants, and consequently, fewer patients developed long COVID during that time. 

One of those who did is Yeng Chang, age 40 years, a family doctor who lives in Sherwood Park, Alberta, Canada. Chang developed long COVID during fall 2022 after getting the virus in June. By then, she’d been vaccinated three times, but she isn’t surprised that she got sick because each vaccine she had was developed before Omicron.

“When I had COVID I was really sick, but I was well enough to stay home,” she said. “I think if I didn’t have my immunizations, I might have been hospitalized, and I don’t know what would have happened.” 

Long COVID has left Chang with brain fog, fatigue, and a lack of physical stamina that forced her to pause her medical practice. For the past year and a half, she’s spent more time as a patient than a physician. 

Chang had her fifth COVID vaccination in the fall and recommends that others do the same. “The booster you got however many years ago was effective for the COVID of that time but there is a new COVID now. You can’t just say, ‘I had one and I’m fine forever.’” 
 

A version of this article appeared on Medscape.com.

Though many people remain on the fence about getting the latest COVID vaccine booster, new research suggests a strong argument for getting the shot this winter: It sharply reduces the risk for COVID. 

Researchers found that getting vaccinated led to a 69% reduction in long-COVID risk among adults who received three vaccines before being infected. The risk reduction was 37% for those who received two doses. Experts say the research provides a strong argument for getting the vaccine, noting that about 10% of people infected with COVID go on to have long COVID, which can be debilitating for one quarter of those with long-lasting symptoms.

The data come from a systematic literature review and meta-analysis published in October in Antimicrobial Stewardship & Epidemiology. Researchers examined 32 studies published between December 2019 and June 2023, involving 775,931 adults. Twenty-four studies, encompassing 620,221 individuals, were included in the meta-analysis. 

“The body of evidence from all these different studies converge on one single reality — that vaccines reduce the risk of long COVID, and people who keep up to date on their vaccinations also fared better than people who got it once or twice and didn’t follow up,” said Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University in St Louis. 

Researchers have reported similar results for children. The National Institutes of Health RECOVER Initiative team found that vaccines are up to 42% effective in preventing long COVID in children, said Dr. Carlos Oliveira, MD, a pediatric infectious diseases specialist and Yale researcher who contributed to the study, which is in preprint. 

Vaccines also protect children from multisystem inflammatory syndrome, a condition that can happen after COVID, as well as protect against other COVID-related problems, such as missed school days, Oliveira said. “Even if the vaccine doesn’t completely stop long COVID, it’s still good for kids to get vaccinated for all these other reasons.” 

However, uptake for the latest boosters has been slow: the Centers for Disease Control and Prevention reported that by mid-November, less than 16% of people aged 18 years or older had received a shot. For children, the number was closer to 6%. A recent Kaiser Family Foundation survey found that booster rates for adults are similar to what it was 1 year ago. 

The survey results suggest that people are no longer as worried about COVID, which is why there is less concerned about keeping up with boosters. Though the current mutation of the virus is not as debilitating as its predecessors, long COVID continues to be a problem: as of January 2023, 28% of people who had contracted the virus had experienced long-COVID symptoms. And though the mechanisms are still not fully understood, and researchers have yet to agree on a definition of long COVID, they are certain about this much: The best way to avoid it is to avoid getting infected to begin with. 

The lack of a diagnostic test for long COVID and the fact that the symptoms mimic those of other diseases lead to inconsistency that can make studies hard to replicate. In the papers reviewed for the Antimicrobial Stewardship & Epidemiology study, long COVID was defined as having symptoms lasting from more than 4 weeks to more than 6 months. Alexandre Marra, MD, the lead author and a researcher at the Hospital Israelita Albert Einstein, in São Paulo, Brazil, and at the University of Iowa, said that a clear standard definition is needed to better understand the actual prevalence and evaluate vaccine effectiveness. 

Al-Aly noted that there is a logical explanation for one finding in the paper: The percentage of individuals who had COVID and reported that long-COVID symptoms declined from 19% in June 2022 to 11% in January 2023. 

Because a pandemic is a dynamic event, constantly producing different variants with different phenotypes, the prevalence of disease is naturally going to be affected. “People who got infected early in the pandemic may have a different long COVID profile and long COVID risk than people who got infected in the second or third year of the pandemic,” Al-Aly said. 

Most of the studies reported data from before the Omicron-variant era. Only eight reported data during that era. Omicron was not as lethal as previous variants, and consequently, fewer patients developed long COVID during that time. 

One of those who did is Yeng Chang, age 40 years, a family doctor who lives in Sherwood Park, Alberta, Canada. Chang developed long COVID during fall 2022 after getting the virus in June. By then, she’d been vaccinated three times, but she isn’t surprised that she got sick because each vaccine she had was developed before Omicron.

“When I had COVID I was really sick, but I was well enough to stay home,” she said. “I think if I didn’t have my immunizations, I might have been hospitalized, and I don’t know what would have happened.” 

Long COVID has left Chang with brain fog, fatigue, and a lack of physical stamina that forced her to pause her medical practice. For the past year and a half, she’s spent more time as a patient than a physician. 

Chang had her fifth COVID vaccination in the fall and recommends that others do the same. “The booster you got however many years ago was effective for the COVID of that time but there is a new COVID now. You can’t just say, ‘I had one and I’m fine forever.’” 
 

A version of this article appeared on Medscape.com.

Though many people remain on the fence about getting the latest COVID vaccine booster, new research suggests a strong argument for getting the shot this winter: It sharply reduces the risk for COVID. 

Researchers found that getting vaccinated led to a 69% reduction in long-COVID risk among adults who received three vaccines before being infected. The risk reduction was 37% for those who received two doses. Experts say the research provides a strong argument for getting the vaccine, noting that about 10% of people infected with COVID go on to have long COVID, which can be debilitating for one quarter of those with long-lasting symptoms.

The data come from a systematic literature review and meta-analysis published in October in Antimicrobial Stewardship & Epidemiology. Researchers examined 32 studies published between December 2019 and June 2023, involving 775,931 adults. Twenty-four studies, encompassing 620,221 individuals, were included in the meta-analysis. 

“The body of evidence from all these different studies converge on one single reality — that vaccines reduce the risk of long COVID, and people who keep up to date on their vaccinations also fared better than people who got it once or twice and didn’t follow up,” said Ziyad Al-Aly, MD, a clinical epidemiologist at Washington University in St Louis. 

Researchers have reported similar results for children. The National Institutes of Health RECOVER Initiative team found that vaccines are up to 42% effective in preventing long COVID in children, said Dr. Carlos Oliveira, MD, a pediatric infectious diseases specialist and Yale researcher who contributed to the study, which is in preprint. 

Vaccines also protect children from multisystem inflammatory syndrome, a condition that can happen after COVID, as well as protect against other COVID-related problems, such as missed school days, Oliveira said. “Even if the vaccine doesn’t completely stop long COVID, it’s still good for kids to get vaccinated for all these other reasons.” 

However, uptake for the latest boosters has been slow: the Centers for Disease Control and Prevention reported that by mid-November, less than 16% of people aged 18 years or older had received a shot. For children, the number was closer to 6%. A recent Kaiser Family Foundation survey found that booster rates for adults are similar to what it was 1 year ago. 

The survey results suggest that people are no longer as worried about COVID, which is why there is less concerned about keeping up with boosters. Though the current mutation of the virus is not as debilitating as its predecessors, long COVID continues to be a problem: as of January 2023, 28% of people who had contracted the virus had experienced long-COVID symptoms. And though the mechanisms are still not fully understood, and researchers have yet to agree on a definition of long COVID, they are certain about this much: The best way to avoid it is to avoid getting infected to begin with. 

The lack of a diagnostic test for long COVID and the fact that the symptoms mimic those of other diseases lead to inconsistency that can make studies hard to replicate. In the papers reviewed for the Antimicrobial Stewardship & Epidemiology study, long COVID was defined as having symptoms lasting from more than 4 weeks to more than 6 months. Alexandre Marra, MD, the lead author and a researcher at the Hospital Israelita Albert Einstein, in São Paulo, Brazil, and at the University of Iowa, said that a clear standard definition is needed to better understand the actual prevalence and evaluate vaccine effectiveness. 

Al-Aly noted that there is a logical explanation for one finding in the paper: The percentage of individuals who had COVID and reported that long-COVID symptoms declined from 19% in June 2022 to 11% in January 2023. 

Because a pandemic is a dynamic event, constantly producing different variants with different phenotypes, the prevalence of disease is naturally going to be affected. “People who got infected early in the pandemic may have a different long COVID profile and long COVID risk than people who got infected in the second or third year of the pandemic,” Al-Aly said. 

Most of the studies reported data from before the Omicron-variant era. Only eight reported data during that era. Omicron was not as lethal as previous variants, and consequently, fewer patients developed long COVID during that time. 

One of those who did is Yeng Chang, age 40 years, a family doctor who lives in Sherwood Park, Alberta, Canada. Chang developed long COVID during fall 2022 after getting the virus in June. By then, she’d been vaccinated three times, but she isn’t surprised that she got sick because each vaccine she had was developed before Omicron.

“When I had COVID I was really sick, but I was well enough to stay home,” she said. “I think if I didn’t have my immunizations, I might have been hospitalized, and I don’t know what would have happened.” 

Long COVID has left Chang with brain fog, fatigue, and a lack of physical stamina that forced her to pause her medical practice. For the past year and a half, she’s spent more time as a patient than a physician. 

Chang had her fifth COVID vaccination in the fall and recommends that others do the same. “The booster you got however many years ago was effective for the COVID of that time but there is a new COVID now. You can’t just say, ‘I had one and I’m fine forever.’” 
 

A version of this article appeared on Medscape.com.

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

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

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

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

One of the biggest challenges facing clinicians who treat long COVID is a lack of consensus when it comes to recognizing and diagnosing the condition. But a new study suggests testing for certain biomarkers may identify long COVID with accuracy approaching 80%.

Effective diagnostic testing would be a game-changer in the long COVID fight, for it’s not just the fatigue, brain fog, heart palpitations, and other persistent symptoms that affect patients. Two out of three people with long COVID also suffer mental health challenges like depression and anxiety. Some patients say their symptoms are not taken seriously by their doctors. And as many as 12% of long COVID patients are unemployed because of the severity of their illness and their employers may be skeptical of their condition.

Quick, accurate diagnosis would eliminate all that. Now a new preprint study suggests that the elevation of certain immune system proteins are a commonality in long COVID patients and identifying them may be an accurate way to diagnose the condition.

Researchers at Cardiff (Wales) University, tracked 166 patients, 79 of whom had been diagnosed with long COVID and 87 who had not. All participants had recovered from a severe bout of acute COVID-19.

In an analysis of the blood plasma of the study participants, researchers found elevated levels of certain components. Four proteins in particular – Ba, iC3b, C5a, and TCC – predicted the presence of long COVID with 78.5% accuracy.

“I was gobsmacked by the results. We’re seeing a massive dysregulation in those four biomarkers,” says study author Wioleta Zelek, PhD, a research fellow at Cardiff University. “It’s a combination that we showed was predictive of long COVID.” 

The study revealed that long COVID was associated with inflammation of the immune system causing these complement proteins to remain dysregulated. Proteins like C3, C4, and C5 are important parts of the immune system because they recruit phagocytes, cells that attack and engulf bacteria and viruses at the site of infection to destroy pathogens like SARS-coV-2. 

In the case of long COVID, these proteins remain chronically elevated. While the symptoms of long COVID have seemed largely unrelated to one another, researchers point to elevated inflammation as a connecting factor that causes various systems in the body to go haywire.

“Anything that could help to better diagnose patients with long COVID is research we’re greatly appreciative of within the clinical community,” said Nisha Viswanathan, MD, director of the University of California, Los Angeles, Long COVID program at UCLA Health. 

Testing for biomarkers highlighted in the study, as well as others like serotonin and cortisol, may help doctors separate patients who have long COVID from patients who have similar symptoms caused by other conditions, said Dr. Viswanathan. For example, a recent study published in the journal Cell found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but recovered from the condition.

Dr. Viswanathan cautions that the biomarker test does not answer all the questions about diagnosing long COVID. For example, Dr. Viswanathan said scientists don’t know whether complement dysregulation is caused by long COVID and not another underlying medical issue that patients had prior to infection, because “we don’t know where patients’ levels were prior to developing long COVID.” For example, those with autoimmune issues are more likely to develop long COVID, which means their levels could have been elevated prior to a COVID infection.

It is increasingly likely, said Dr. Viswanathan, that long COVID is an umbrella term for a host of conditions that could be caused by different impacts of the virus. Other research has pointed to the different phenotypes of long COVID. For example, some are focused on cardiopulmonary issues and others on fatigue and gastrointestinal problems. 

“It looks like these different phenotypes have a different mechanism for disease,” she said. This means that it’s less likely to be a one-size-fits-all condition and the next step in the research should be identifying which biomarker is aligned with which phenotype of the disease. 

Better diagnostics will open the door to better treatments, Dr. Zelek said. The more doctors understand about the mechanism causing immune dysregulation in long COVID patients, the more they can treat it with existing medications. Dr. Zelek’s lab has been studying certain medications like pegcetacoplan (C3 blocker), danicopan (anti-factor D), and iptacopan (anti-factor B) that can be used to break the body’s cycle of inflammation and reduce symptoms experienced in those with long COVID. 

These drugs are approved by the U.S. Food and Drug Administration for the treatment of a rare blood disease called paroxysmal nocturnal hemoglobinuria. The C5 inhibitor zilucoplan has also been used in patients hospitalized with COVID-19 and researchers have found that the drug lowered serum C5 and interleukin-8 concentration in the blood, seeming to reduce certain aspects of the immune system’s inflammatory response to the virus. 

The Cardiff University research is one of the most detailed studies to highlight long COVID biomarkers to date, said infectious disease specialist Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. The research needs to be duplicated in a larger study population that might include the other biomarkers like serotonin and cortisol to see if they’re related, she said. 

Researchers are learning more everyday about the various biomarkers that may be linked to long COVID, she added. This Cardiff study showed that a huge percentage of those patients had elevated levels of certain complements. The next step, said Dr. McComsey, “is to put all these puzzle pieces together” so that clinicians have a common diagnostic tool or tools that provide patients with some peace of mind in starting their road to recovery.

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

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

As many as 87% of patients experience symptoms after COVID-19 infection that last 2 months or more, one of the most common being chest pain. And chronic chest discomfort may persist in some individuals for years after COVID, warranting future studies of reliable treatments and pain management in this population, a new study shows.

“Recent studies have shown that chest pain occurs in as many as 89% of patients who qualify as having long COVID,” said Ansley Poole, an undergraduate student at the University of South Florida, Tampa, who conducted the research under the supervision of Christine Hunt, DO, and her colleagues at Mayo Clinic, Jacksonville, Fla.

The findings, though preliminary, shed light on the prevalence, current treatments, and ongoing challenges in managing symptoms of long COVID, said Ms. Poole, who presented the research at the annual Pain Medicine Meeting sponsored by the American Society of Regional Anesthesia and Pain Medicine.

Long COVID, which affects an estimated 18 million Americans, manifests approximately 12 weeks after the initial infection and can persist for 2 months or more. Ms. Poole and her team set out to identify risk factors, treatment options, and outcomes for patients dealing with post-COVID chest discomfort.

The study involved a retrospective chart review of 520 patients from the Mayo Clinic network, narrowed down to a final sample of 104. To be included, patients had to report chest discomfort 3-6 months post COVID that continued for 3-6 months after presentation, with no history of chronic chest pain before the infection.

The researchers identified no standardized method for the treatment or management of chest pain linked to long COVID. “Patients were prescribed multiple different treatments, including opioids, post-COVID treatment programs, anticoagulants, steroids, and even psychological programs,” Ms. Poole said.

The median age of the patients was around 50 years; more than 65% were female and over 90% identified as White. More than half (55%) had received one or more vaccine doses at the time of infection. The majority were classified as overweight or obese at the time of their SARS-CoV-2 infection.

Of the 104 patients analyzed, 30 were referred to one or more subspecialties within the pain medicine department, 23 were hospitalized, and 9 were admitted to the intensive care unit or critical care.

“Fifty-three of our patients visited the ER one or more times after COVID because of chest discomfort; however, only six were admitted for over 24 hours, indicating possible overuse of emergency services,” Ms. Poole noted.

Overall, chest pain was described as intermittent instead of constant, which may have been a barrier to providing adequate and timely treatment. The inconsistent presence of pain contributed to the prolonged suffering some patients experienced, Ms. Poole noted.

The study identified several comorbidities, potentially complicating the treatment and etiology of chest pain. These comorbidities – when combined with COVID-related chest pain – contributed to the wide array of prescribed treatments, including steroids, anticoagulants, beta blockers, and physical therapy. Chest pain also seldom stood alone; it was often accompanied by other long COVID–related symptoms, such as shortness of breath.

“Our current analysis indicates that chest pain continues on for years in many individuals, suggesting that COVID-related chest pain may be resistant to treatment,” Ms. Poole reported.

The observed heterogeneity in treatments and outcomes in patients experiencing long-term chest discomfort after COVID infection underscores the need for future studies to establish reliable treatment and management protocols for this population, said Dalia Elmofty, MD, an associate professor of anesthesia and critical care at the University of Chicago, who was not involved in the study. “There are things about COVID that we don’t fully understand. As we’re seeing its consequences and trying to understand its etiology, we recognize the need for further research,” Dr. Elmofty said.

“So many different disease pathologies came out of COVID, whether it’s organ pathology, myofascial pathology, or autoimmune pathology, and all of that is obviously linked to pain,” Dr. Elmofty told this news organization. “It’s an area of research that we are going to have to devote a lot of time to in order to understand, but I think we’re still in the very early phases, trying to fit the pieces of the puzzle together.”

Ms. Poole and Dr. Elmofty report no relevant financial relationships.

A version of this article appeared on Medscape.com.

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Long COVID can exacerbate existing mental health disorders or cause new-onset psychiatric symptoms, but mental illness does not cause long COVID, experts say.

The consensus guidance statement on the assessment and treatment of mental health symptoms in patients with post-acute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID, was published online in Physical Medicine and Rehabilitation, the journal of the American Academy of Physical Medicine and Rehabilitation (AAPM&R).

The statement was developed by a task force that included experts from physical medicine, neurology, neuropsychiatry, neuropsychology, rehabilitation psychology, and primary care. It is the eighth guidance statement on long COVID published by AAPM&R).

“Many of our patients have reported experiences in which their symptoms of long COVID have been dismissed either by loved ones in the community, or also amongst health care providers, and they’ve been told their symptoms are in their head or due to a mental health condition, but that’s simply not true,” Abby L. Cheng, MD, a physiatrist at Barnes Jewish Hospital in St. Louis and a coauthor of the new guidance, said in a press briefing.

“Long COVID is real, and mental health conditions do not cause long COVID,” Dr. Cheng added.
 

Millions of Americans affected

Anxiety and depression have been reported as the second and third most common symptoms of long COVID, according to the guidance statement.

There is some evidence that the body’s inflammatory response – specifically, circulating cytokines – may contribute to the worsening of mental health symptoms or may bring on new symptoms of anxiety or depression, said Dr. Cheng. Cytokines may also affect levels of brain chemicals, such as serotonin, she said.

Researchers are also exploring whether the persistence of virus in the body, miniature blood clots in the body and brain, and changes to the gut microbiome affect the mental health of people with long COVID.

Some mental health symptoms – such as fatigue, brain fog, sleep disturbances, and tachycardia – can mimic long COVID symptoms, said Dr. Cheng.

The treatment is the same for someone with or without long COVID who has anxiety, depression, posttraumatic stress disorder, or other mental health conditions and includes treatment of coexisting medical conditions, supportive therapy and cognitive-behavioral therapy, and pharmacologic interventions, she said.

“Group therapy may have a particular role in the long COVID population because it really provides that social connection and awareness of additional resources in addition to validation of their experiences,” Dr. Cheng said.

The guidance suggests that primary care practitioners – if it’s within their comfort zone and they have the training – can be the first line for managing mental health symptoms.

But for patients whose symptoms are interfering with functioning and their ability to interact with the community, the guidance urges primary care clinicians to refer the patient to a specialist.

“It leaves the door open to them to practice within their scope but also gives guidance as to how, why, and who should be referred to the next level of care,” said Dr. Cheng.

Coauthor Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine at UT Health San Antonio, Texas, said that although fewer people are now getting long COVID, “it’s still an impactful number.”

The Centers for Disease Control and Prevention recently estimated that about 7% of American adults (18 million) and 1.3% of children had experienced long COVID.

Dr. Gutierrez said that it’s an evolving number, as some patients who have a second or third or fourth SARS-CoV-2 infection experience exacerbations of previous bouts of long COVID or develop long COVID for the first time.

“We are still getting new patients on a regular basis with long COVID,” said AAPM&R President Steven R. Flanagan, MD, a physical medicine specialist.

“This is a problem that really is not going away. It is still real and still ever-present,” said Dr. Flanagan, chair of rehabilitation medicine at NYU Langone Health.
 

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

Good news for people struggling with sensory problems after a bout of COVID-19. Although mild cases of the disease often impair the ability to taste and smell, and the problem can drag on for months, a new study from Italy shows that most people return to their senses, as it were, within 3 years.

“In the vast majority of cases, the loss of the sense of smell is not irreversible,” said Paolo Boscolo-Rizzo, MD, a professor of medicine, surgery, and health sciences at the University of Trieste (Italy), and a co-author of the study, published as a research letter in JAMA Otolaryngology–Head & Neck Surgery.

Dr. Boscolo-Rizzo and his colleagues analyzed data from 88 adults with mild COVID-19, which was defined as having no lower respiratory disease and blood oxygen saturation of 94% or greater. Another group of 88 adults who never contracted the virus but sometimes had difficulties with smell and taste were also studied. In both groups, the average age was 49 years, all participants were White, and 58% were women.

The researchers tested participants’ sense of smell with sticks that contained different odors and checked their sense of taste with strips that had different tastes. Over time, fewer people had difficulty distinguishing odors. Three years after developing COVID-19, only 12 people had impaired smell, compared with 36 people at year 1 and 24 people at year 2. And at the 3-year mark, all participants had at least a partial ability to smell. 

The story was similar with sense of taste, with 10 of 88 people reporting impairments 3 years later. By then, people with COVID-19 were no more likely to have trouble with smell or taste than people who did not get the virus. 

A study this past June showed a strong correlation between severity of COVID-19 symptoms and impaired sense of taste and smell and estimated that millions of Americans maintained altered senses. More than 10% of people in the Italian study still had trouble with smell or taste 3 years later.
 

Emerging treatments, psychological concerns

“We’re seeing fewer people with this problem, but there are still people suffering from it,” said Fernando Carnavali, MD, an internal medicine physician and a site director for the Center for Post-COVID Care at the Icahn School of Medicine at Mount Sinai, New York City.

Dr. Carnavali wasn’t part of this study, but he did find the new results encouraging, and he called for similar studies in diverse populations that have experienced COVID-19. He also noted that an impaired sense of smell is distressing.

“It really has a significant psychological impact,” Dr. Carnavali said.

He recalled a patient crying in his office because her inability to smell made it impossible for her to cook. Dr. Carnavali recommended clinicians refer patients facing protracted loss of smell or taste to mental health professionals for support.

Treatments are emerging for COVID-19 smell loss. One approach is to inject platelet-rich plasma into a patient’s nasal cavities to help neurons related to smell repair themselves.

A randomized trial showed platelet-rich plasma significantly outperformed placebo in patients with smell loss up to a year after getting COVID-19.

“I wish more people would do it,” said Zara Patel, MD, an otolaryngologist at Stanford (Calif.) Medicine, who helped conduct that trial. She said some physicians may be nervous about injecting plasma so close to the skull and are therefore hesitant to try this approach. 

Another technique may help to address the olfactory condition known as parosmia, in which patients generally experience a benign odor as rancid, according to otolaryngologist Nyssa Farrell, MD, of Washington University School of Medicine, St. Louis. Dr. Farrell said around two-thirds of patients who contract COVID-19 develop the condition, and the rates of long-term parosmia range from 10%-50% depending on various studies.

“It is almost always foul; this can profoundly affect someone’s quality of life,” impairing their ability to eat or to be intimate with a partner who now smells unpleasant, said Dr. Farrell, who wasn’t associated with this research.

The treatment, called a stellate ganglion block, is provided through a shot into nerves in the neck. People with parosmia associated with COVID-19 often report that this method cures them. Dr. Patel said that may be because their psychological health is improving, not their sense of smell, because the area of the body where the stellate ganglion block is applied is not part of the olfactory system.

Earlier this year, Dr. Farrell and colleagues reported that parosmia linked to COVID-19 is associated with an increased risk for depression, anxiety, and suicidal ideation. 

One coauthor reported receiving grants from Smell and Taste Lab, Takasago, Baia Foods, and Frequency Therapeutics. The other authors reported no relevant financial relationships.

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

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

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

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

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

Could antidepressants hold the key to treating long COVID? University of Pennsylvania researchers have uncovered a link between long COVID and levels of serotonin in the body that may offer a new explanation for the condition. The study even points to a possible treatment.

Serotonin is a neurotransmitter that has many functions in the body and is targeted by the most commonly prescribed antidepressants – the selective serotonin reuptake inhibitors.

Serotonin is widely studied for its effects on the brain – it regulates the messaging between neurons, affecting sleep, mood, and memory. It is present in the gut, is found in cells along the gastrointestinal tract, and is absorbed by blood platelets. Gut serotonin, known as circulating serotonin, is responsible for a host of other functions, including the regulation of blood flow, body temperature, and digestion.

Low levels of serotonin could result in any number of seemingly unrelated symptoms, as in the case of long COVID, experts say. The condition affects about 7% of Americans and is associated with a wide range of health problems, including fatigue, shortness of breath, neurological symptoms, joint pain, blood clots, heart palpitations, and digestive problems.

Long COVID is difficult to treat because researchers haven’t been able to pinpoint the underlying mechanisms that cause prolonged illness after a SARS-CoV-2 infection, said study author Christoph A. Thaiss, PhD, an assistant professor of microbiology at the Perelman School of Medicine at the University of Pennsylvania.

The hope is that this study could have implications for new treatments, he said.

“Long COVID can have manifestations not only in the brain but in many different parts of the body, so it’s possible that serotonin reductions are involved in many different aspects of the disease,” said Dr. Thaiss.

Dr. Thaiss’s study, published in the journal Cell, found lower serotonin levels in long COVID patients, compared with patients who were diagnosed with acute COVID-19 but who fully recovered.

His team found that reductions in serotonin were driven by low levels of circulating SARS-CoV-2 virus that caused persistent inflammation as well as an inability of the body to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactive blood platelets were also shown to play a role; they serve as the primary means of serotonin absorption.

The study doesn’t make any recommendations for treatment, but understanding the role of serotonin in long COVID opens the door to a host of novel ideas that could set the stage for clinical trials and affect care.

“The study gives us a few possible targets that could be used in future clinical studies,” Dr. Thaiss said.

Persistent circulating virus is one of the drivers of low serotonin levels, said study author Michael Peluso, MD, an assistant research professor of infectious medicine at the University of California, San Francisco, School of Medicine. This points to the need to reduce viral load using antiviral medications like nirmatrelvir/ritonavir (Paxlovid), which is approved by the U.S. Food and Drug Administration for the treatment of COVID-19, and VV116, which has not yet been approved for use against COVID.

Research published in the New England Journal of Medicine found that the oral antiviral agent VV116 was as effective as nirmatrelvir/ritonavir in reducing the body’s viral load and aiding recovery from SARS-CoV-2 infection. Paxlovid has also been shown to reduce the likelihood of getting long COVID after an acute SARS-CoV-2 infection.

Researchers are investigating ways to target serotonin levels directly, potentially using SSRIs. But first they need to study whether improvement in serotonin level makes a difference.

“What we need now is a good clinical trial to see whether altering levels of serotonin in people with long COVID will lead to symptom relief,” Dr. Peluso said.

Indeed, the research did show that the SSRI fluoxetine, as well as a glycine-tryptophan supplement, improved cognitive function in SARS-CoV-2-infected rodent models, which were used in a portion of the study.

David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City, said the research is helping “to paint a biological picture” that’s in line with other research on the mechanisms that cause long COVID symptoms.

But Dr. Putrino, who was not involved in the study, cautions against treating long COVID patients with SSRIs or any other treatment that increases serotonin before testing patients to determine whether their serotonin levels are actually lower than those of healthy persons.

“We don’t want to assume that every patient with long COVID is going to have lower serotonin levels,” said Dr. Putrino.

What’s more, researchers need to investigate whether SSRIs increase levels of circulating serotonin. It’s important to note that researchers found lower levels of circulating serotonin but that serotonin levels in the brain remained normal.

Traditionally, SSRIs are used clinically for increasing the levels of serotonin in the brain, not the body.

“Whether that’s going to contribute to an increase in systemic levels of serotonin, that’s something that needs to be tested,” said Akiko Iwasaki, PhD, co-lead investigator of the Yale School of Medicine, New Haven, Conn., COVID-19 Recovery Study, who was not involved in the research.

Thus far, investigators have not identified one unifying biomarker that seems to cause long COVID in all patients, said Dr. Iwasaki. Some research has found higher levels of certain immune cells and biomarkers: for example, monocytes and activated B lymphocytes, indicating a stronger and ongoing antibody response to the virus. Other recent research conducted by Dr. Iwasaki, Dr. Putrino, and others, published in the journal Nature, showed that long COVID patients tend to have lower levels of cortisol, which could be a factor in the extreme fatigue experienced by many who suffer from the condition.

The findings in the study in The Cell are promising, but they need to be replicated in more people, said Dr. Iwasaki. And even if they’re replicated in a larger study population, this would still be just one biomarker that is associated with one subtype of the disease. There is a need to better understand which biomarkers go with which symptoms so that the most effective treatments can be identified, she said.

Both Dr. Putrino and Dr. Iwasaki contended that there isn’t a single factor that can explain all of long COVID. It’s a complex disease caused by a host of different mechanisms.

Still, low levels of serotonin could be an important piece of the puzzle. The next step, said Dr. Iwasaki, is to uncover how many of the millions of Americans with long COVID have this biomarker.

“People working in the field of long COVID should now be considering this pathway and thinking of ways to measure serotonin in their patients.”

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