New Data: Long COVID Cases Surge

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Mon, 04/01/2024 - 17:18

 

Experts worry a recent rise in long COVID cases — fueled by a spike in winter holiday infections and a decline in masking and other measures — could continue into this year.

A sudden rise in long COVID in January has persisted into a second month. About 17.6% of those surveyed by the Census Bureau in January said they have experienced long COVID. The number for February was 17.4.

Compare these new numbers to October 2023 and earlier, when long COVID numbers hovered between 14% and 15% of the US adult population as far back as June 2022.

The Census Bureau and the Centers for Disease Control and Prevention (CDC) regularly query about 70,000 people as part of its ongoing Pulse Survey.

It’s Not Just the Federal Numbers

Independently, advocates, researchers, and clinicians also reported seeing an increase in the number of people who have developed long COVID after a second or third infection.

John Baratta, MD, who runs the COVID Recovery Clinic at the University of North Carolina, said the increase is related to a higher rate of acute cases in the fall and winter of 2023.

In January, the percentage of North Carolinians reporting ever having had long COVD jumped from 12.5% to 20.2% in January and fell to 16.8% in February.

At the same time, many cases are either undetected or unreported by people who tested positive for COVID-19 at home or are not aware they have had it.

Hannah Davis, a member of the Patient-Led Research Collaborative, also linked the increase in long COVID to the wave of new infections at the end of 2023 and the start of 2024.

“It’s absolutely real,” she said via email. “There have been many new cases in the past few months, and we see those new folks in our communities as well.”

Wastewater Remains the Best Indicator

“This results in many cases of COVID flying under the radar,” Dr. Baratta said. “However, we do know from the wastewater monitoring that there was a pretty substantial rise.”

Testing wastewater for COVID levels is becoming one of the most reliable measures of estimating infection, he said. Nationally, viral measure of wastewater followed a similar path: The viral rate started creeping up in October and peaked on December 30, according to CDC measures.

RNA extracted from concentrated wastewater samples offer a good measure of SARS-CoV-2 in the community. In North Carolina and elsewhere, the state measures the virus by calculating gene copies in wastewater per capita — how many for each resident. For most of 2023, North Carolina reported fewer than 10 million viral gene copies per state resident. In late July, that number shot up to 25 million and reached 71 million per capita in March 2023 before starting to go down.

Repeat Infections, Vaccine Apathy Driving Numbers

Dr. Baratta said COVID remains a problem in rural areas. In Maine, wastewater virus counts have been much higher than the national average. There, the percentage of people who reported currently experiencing long COVID rose from 5.7% in October to 9.2% in January. The percentage reporting ever experiencing long COVID rose from 13.8% to 21% in that period.

 

 

Other factors play a role. Dr. Baratta said he is seeing patients with long COVID who have refused the vaccine or developed long COVID after a second or third infection.

He said he thinks that attitudes toward the pandemic have resulted in relaxed protection and prevention efforts.

“There is low booster vaccination rate and additional masking is utilized less that before,” he said. About 20% of the population has received the latest vaccine booster, according to the Kaiser Family Foundation.

The increase in long COVID has many causes including “infection, reinfection (eg, people getting COVID after a second, third, or fourth infection), low vaccination rates, waning immunity, and decline in the use of antivirals (such as Paxlovid),” said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, St. Louis, Missouri.

“All of these could contribute to the rise in burden of long COVID,” he said.

Not all states reported an increase. Massachusetts and Hawaii saw long COVD rates drop slightly, according to the CDC.

A version of this article appeared on Medscape.com.

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Experts worry a recent rise in long COVID cases — fueled by a spike in winter holiday infections and a decline in masking and other measures — could continue into this year.

A sudden rise in long COVID in January has persisted into a second month. About 17.6% of those surveyed by the Census Bureau in January said they have experienced long COVID. The number for February was 17.4.

Compare these new numbers to October 2023 and earlier, when long COVID numbers hovered between 14% and 15% of the US adult population as far back as June 2022.

The Census Bureau and the Centers for Disease Control and Prevention (CDC) regularly query about 70,000 people as part of its ongoing Pulse Survey.

It’s Not Just the Federal Numbers

Independently, advocates, researchers, and clinicians also reported seeing an increase in the number of people who have developed long COVID after a second or third infection.

John Baratta, MD, who runs the COVID Recovery Clinic at the University of North Carolina, said the increase is related to a higher rate of acute cases in the fall and winter of 2023.

In January, the percentage of North Carolinians reporting ever having had long COVD jumped from 12.5% to 20.2% in January and fell to 16.8% in February.

At the same time, many cases are either undetected or unreported by people who tested positive for COVID-19 at home or are not aware they have had it.

Hannah Davis, a member of the Patient-Led Research Collaborative, also linked the increase in long COVID to the wave of new infections at the end of 2023 and the start of 2024.

“It’s absolutely real,” she said via email. “There have been many new cases in the past few months, and we see those new folks in our communities as well.”

Wastewater Remains the Best Indicator

“This results in many cases of COVID flying under the radar,” Dr. Baratta said. “However, we do know from the wastewater monitoring that there was a pretty substantial rise.”

Testing wastewater for COVID levels is becoming one of the most reliable measures of estimating infection, he said. Nationally, viral measure of wastewater followed a similar path: The viral rate started creeping up in October and peaked on December 30, according to CDC measures.

RNA extracted from concentrated wastewater samples offer a good measure of SARS-CoV-2 in the community. In North Carolina and elsewhere, the state measures the virus by calculating gene copies in wastewater per capita — how many for each resident. For most of 2023, North Carolina reported fewer than 10 million viral gene copies per state resident. In late July, that number shot up to 25 million and reached 71 million per capita in March 2023 before starting to go down.

Repeat Infections, Vaccine Apathy Driving Numbers

Dr. Baratta said COVID remains a problem in rural areas. In Maine, wastewater virus counts have been much higher than the national average. There, the percentage of people who reported currently experiencing long COVID rose from 5.7% in October to 9.2% in January. The percentage reporting ever experiencing long COVID rose from 13.8% to 21% in that period.

 

 

Other factors play a role. Dr. Baratta said he is seeing patients with long COVID who have refused the vaccine or developed long COVID after a second or third infection.

He said he thinks that attitudes toward the pandemic have resulted in relaxed protection and prevention efforts.

“There is low booster vaccination rate and additional masking is utilized less that before,” he said. About 20% of the population has received the latest vaccine booster, according to the Kaiser Family Foundation.

The increase in long COVID has many causes including “infection, reinfection (eg, people getting COVID after a second, third, or fourth infection), low vaccination rates, waning immunity, and decline in the use of antivirals (such as Paxlovid),” said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, St. Louis, Missouri.

“All of these could contribute to the rise in burden of long COVID,” he said.

Not all states reported an increase. Massachusetts and Hawaii saw long COVD rates drop slightly, according to the CDC.

A version of this article appeared on Medscape.com.

 

Experts worry a recent rise in long COVID cases — fueled by a spike in winter holiday infections and a decline in masking and other measures — could continue into this year.

A sudden rise in long COVID in January has persisted into a second month. About 17.6% of those surveyed by the Census Bureau in January said they have experienced long COVID. The number for February was 17.4.

Compare these new numbers to October 2023 and earlier, when long COVID numbers hovered between 14% and 15% of the US adult population as far back as June 2022.

The Census Bureau and the Centers for Disease Control and Prevention (CDC) regularly query about 70,000 people as part of its ongoing Pulse Survey.

It’s Not Just the Federal Numbers

Independently, advocates, researchers, and clinicians also reported seeing an increase in the number of people who have developed long COVID after a second or third infection.

John Baratta, MD, who runs the COVID Recovery Clinic at the University of North Carolina, said the increase is related to a higher rate of acute cases in the fall and winter of 2023.

In January, the percentage of North Carolinians reporting ever having had long COVD jumped from 12.5% to 20.2% in January and fell to 16.8% in February.

At the same time, many cases are either undetected or unreported by people who tested positive for COVID-19 at home or are not aware they have had it.

Hannah Davis, a member of the Patient-Led Research Collaborative, also linked the increase in long COVID to the wave of new infections at the end of 2023 and the start of 2024.

“It’s absolutely real,” she said via email. “There have been many new cases in the past few months, and we see those new folks in our communities as well.”

Wastewater Remains the Best Indicator

“This results in many cases of COVID flying under the radar,” Dr. Baratta said. “However, we do know from the wastewater monitoring that there was a pretty substantial rise.”

Testing wastewater for COVID levels is becoming one of the most reliable measures of estimating infection, he said. Nationally, viral measure of wastewater followed a similar path: The viral rate started creeping up in October and peaked on December 30, according to CDC measures.

RNA extracted from concentrated wastewater samples offer a good measure of SARS-CoV-2 in the community. In North Carolina and elsewhere, the state measures the virus by calculating gene copies in wastewater per capita — how many for each resident. For most of 2023, North Carolina reported fewer than 10 million viral gene copies per state resident. In late July, that number shot up to 25 million and reached 71 million per capita in March 2023 before starting to go down.

Repeat Infections, Vaccine Apathy Driving Numbers

Dr. Baratta said COVID remains a problem in rural areas. In Maine, wastewater virus counts have been much higher than the national average. There, the percentage of people who reported currently experiencing long COVID rose from 5.7% in October to 9.2% in January. The percentage reporting ever experiencing long COVID rose from 13.8% to 21% in that period.

 

 

Other factors play a role. Dr. Baratta said he is seeing patients with long COVID who have refused the vaccine or developed long COVID after a second or third infection.

He said he thinks that attitudes toward the pandemic have resulted in relaxed protection and prevention efforts.

“There is low booster vaccination rate and additional masking is utilized less that before,” he said. About 20% of the population has received the latest vaccine booster, according to the Kaiser Family Foundation.

The increase in long COVID has many causes including “infection, reinfection (eg, people getting COVID after a second, third, or fourth infection), low vaccination rates, waning immunity, and decline in the use of antivirals (such as Paxlovid),” said Ziyad Al-Aly, MD, chief of research at Veterans Affairs St. Louis Health Care and clinical epidemiologist at Washington University in St. Louis, St. Louis, Missouri.

“All of these could contribute to the rise in burden of long COVID,” he said.

Not all states reported an increase. Massachusetts and Hawaii saw long COVD rates drop slightly, according to the CDC.

A version of this article appeared on Medscape.com.

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Five Keys to Helping Long-COVID Patients Recover

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Changed
Thu, 03/21/2024 - 12:38

About 7% of US adults report having or having had symptoms of long COVID such as fatigue, heart palpitations and/or dizziness. These are 3 of the 12 symptoms identified as part of the National Institute of Health’s RECOVER initiative that can be reliably used to classify someone as having long COVID.

While there is no standard federally approved treatment for long COVID, physicians can recommend several strategies to their patients to help them recover.

The good news is that many people experience improvements in their symptoms over time by adopting these strategies, said Andrew Schamess, MD, an internal medicine physician at the Ohio State University Wexner Medical Center and director of its Post-COVID Recovery Program. 

1. Pace yourself.

Fatigue and postexertional malaise are 2 of the 12 symptoms used to classify someone as having long COVID. 

“There’s mental, or cognitive, fatigue, where people become exhausted after any span of time trying to do complicated cognitive tasks,” said Dr. Schamess. “There’s also general fatigue, or sleepiness, where after a few hours you feel like you could go right back to sleep.” 

The third category, he added, is postexertional malaise, where patients are exhausted by exercise, either immediately or up to 24-48 hours later.

That’s where a technique known as “pacing” can help. Pacing is an energy-conservation technique often used among people with other disabling conditions, such as chronic fatigue syndrome, said Ravindra Ganesh, MD, an internal medicine physician at the Mayo Clinic in Minnesota who specializes in long COVID.

“I tell patients that they have to figure out what their energy envelope is, which is the fixed amount of energy that they can use every day without crashing,” he said. 

You may be able to handle a daily 30-minute walk, for example, but if you pair it with something cognitively difficult, such as doing your taxes, your fatigue symptoms may flare up. 

“It’s hard advice for my patients to follow, as most are real go-getters,” he said. “But I point out to them that if they aim to minimize crashes, it will help them make slow progress.”

Over time, he said, their energy levels should gradually rise so that they can engage in more and more activity.

2. Follow a plant-based, anti-inflammatory diet.

There’s no research to suggest that following a certain eating pattern will help to reverse long COVID, said Dr. Ganesh. But in general, he said his patients anecdotally report that they feel better when they limit refined sugar and follow a plant-based diet that can help to lower inflammation in the body. 

“It makes sense, because it prevents dramatic blood glucose changes that can cause their body to crash,” he said. He generally recommends an anti-inflammatory diet like the Mediterranean diet, which is rich in fruits, vegetables, whole grains, and mono-unsaturated fat.

Many people with long COVID take an array of supplements, Dr. Ganesh said, although there’s little research to suggest that they may help. He does encourage patients to take about 2 g of an omega-3 supplement, such as fish oil, as it may help to reduce inflammation associated with long COVID

He also recommends fisetin, a dietary flavonoid found in fruits such as strawberries and kiwis. Preliminary research suggests that it may help to combat some of the neurologic damage associated with long COVID. 

“It appears to maintain mitochondrial function and has anti-inflammatory activities,” said Dr. Ganesh.

 

 

3. Modify exercise. 

Most of the time, exercise boosts health and reduces risk for certain diseases. But this strategy may not work for people who have certain symptoms from long COVID, such as postexertional malaise or postural orthostatic tachycardia syndrome (POTS), a condition that causes symptoms such as a fast heart rate, dizziness, and fatigue when transitioning from lying down to standing up. 

“With long-COVID patients, it often has to be symptom-titrated exercise,” said Dr. Schamess. This means physical activity needs to be constantly monitored and adjusted on the basis of a patient’s symptoms. “We need to figure out what they can do that doesn’t provoke their symptoms,” he explained. 

Dr. Schamess often recommends that patients with long COVID, at least initially, focus on exercises in which they are sitting (such as cycling) or prone. 

“The key thing is most people with long COVID can do a lot more exercise in a sitting or lying position than a standing position,” he said. “It’s baffling to them that they can’t walk two blocks but can bike 10 miles.” 

For symptoms like fatigue or postexertional malaise, Dr. Schamess often refers patients to physical therapy to develop an individualized exercise program. A 2022 study published in Scandinavian Journal of Medicine & Science in Sports found that when long-COVID patients completed an 8-week program of three exercise sessions per week, they experienced significant improvements in quality of life, fatigue, muscle strength, and overall fitness compared with a control group. 

“It’s important to make sure that workouts are supervised, so that they can be modified as necessary” said Dr. Schamess. 

4. Take steps to improve sleep quality.

A 2023 study published in the Journal of General Internal Medicine found that about 40% of people with long COVID report sleep issues such as insomnia or not feeling refreshed in the morning. 

“Sleep may become challenging, which can be frustrating for a patient with long COVID who desperately needs rest,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center in New York City.

Some of the simplest ways to improve sleep are common sense; however, these issues never affected the person pre-COVID, so they have to become new habits.

“A lot of my patients with long COVID find that they are more sensitive to caffeine, so they really can’t have it anymore later in the day,” he said. “The same goes for bright screens” such as those on cell phones, tablets, and e-book readers, he said. “They may find that it’s harder for them to fall and stay asleep if they’re on their iPhone right before bed. These are all things that may not have been issues before they were diagnosed with long COVID.”

Dr. Purpura also said that he encourages his patients to practice mindfulness or relaxation exercises before bed, such as deep breathing. One technique he recommends is called box breathing, where the patient inhales for 4 seconds, holds his or her breath for 4 seconds, exhales for 4 seconds, then holds his or her breath again for 4 seconds. Some research suggests that this paced breathing technique, when done for 20 minutes before bed, helps to improve symptoms of insomnia. 

While sleep medications such as zolpidem (Ambien) are often used as short-term relief for insomnia, Dr. Schamess said he has not found them particularly helpful for sleep issues that stem from long COVID. 

“They help patients fall asleep but not necessarily stay asleep, which can be an issue for people with long COVID,” he said.

 

 

5. Consider medications.

No standard drugs or treatments have yet been approved to treat long COVID (although some, such as Paxlovid, are in clinical trials). But some medications may help to relieve symptoms, said Dr. Ganesh. These include:

  • Blood pressure drugs such as beta-blockers now used to treat POTS symptoms
  • Nerve-pain medications such as gabapentin or pregabalin. “These can also help with sleep, since patients don’t have pain to distract them,” said Dr. Ganesh.
  • Low-dose naltrexone to help with fatigue

“There’s not a one-size-fits-all approach to treat long-COVID symptoms,” said Dr. Ganesh. “You really need to work with the patient and possibly even cycle through several different medications before you find one that helps.”

A version of this article appeared on Medscape.com.

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About 7% of US adults report having or having had symptoms of long COVID such as fatigue, heart palpitations and/or dizziness. These are 3 of the 12 symptoms identified as part of the National Institute of Health’s RECOVER initiative that can be reliably used to classify someone as having long COVID.

While there is no standard federally approved treatment for long COVID, physicians can recommend several strategies to their patients to help them recover.

The good news is that many people experience improvements in their symptoms over time by adopting these strategies, said Andrew Schamess, MD, an internal medicine physician at the Ohio State University Wexner Medical Center and director of its Post-COVID Recovery Program. 

1. Pace yourself.

Fatigue and postexertional malaise are 2 of the 12 symptoms used to classify someone as having long COVID. 

“There’s mental, or cognitive, fatigue, where people become exhausted after any span of time trying to do complicated cognitive tasks,” said Dr. Schamess. “There’s also general fatigue, or sleepiness, where after a few hours you feel like you could go right back to sleep.” 

The third category, he added, is postexertional malaise, where patients are exhausted by exercise, either immediately or up to 24-48 hours later.

That’s where a technique known as “pacing” can help. Pacing is an energy-conservation technique often used among people with other disabling conditions, such as chronic fatigue syndrome, said Ravindra Ganesh, MD, an internal medicine physician at the Mayo Clinic in Minnesota who specializes in long COVID.

“I tell patients that they have to figure out what their energy envelope is, which is the fixed amount of energy that they can use every day without crashing,” he said. 

You may be able to handle a daily 30-minute walk, for example, but if you pair it with something cognitively difficult, such as doing your taxes, your fatigue symptoms may flare up. 

“It’s hard advice for my patients to follow, as most are real go-getters,” he said. “But I point out to them that if they aim to minimize crashes, it will help them make slow progress.”

Over time, he said, their energy levels should gradually rise so that they can engage in more and more activity.

2. Follow a plant-based, anti-inflammatory diet.

There’s no research to suggest that following a certain eating pattern will help to reverse long COVID, said Dr. Ganesh. But in general, he said his patients anecdotally report that they feel better when they limit refined sugar and follow a plant-based diet that can help to lower inflammation in the body. 

“It makes sense, because it prevents dramatic blood glucose changes that can cause their body to crash,” he said. He generally recommends an anti-inflammatory diet like the Mediterranean diet, which is rich in fruits, vegetables, whole grains, and mono-unsaturated fat.

Many people with long COVID take an array of supplements, Dr. Ganesh said, although there’s little research to suggest that they may help. He does encourage patients to take about 2 g of an omega-3 supplement, such as fish oil, as it may help to reduce inflammation associated with long COVID

He also recommends fisetin, a dietary flavonoid found in fruits such as strawberries and kiwis. Preliminary research suggests that it may help to combat some of the neurologic damage associated with long COVID. 

“It appears to maintain mitochondrial function and has anti-inflammatory activities,” said Dr. Ganesh.

 

 

3. Modify exercise. 

Most of the time, exercise boosts health and reduces risk for certain diseases. But this strategy may not work for people who have certain symptoms from long COVID, such as postexertional malaise or postural orthostatic tachycardia syndrome (POTS), a condition that causes symptoms such as a fast heart rate, dizziness, and fatigue when transitioning from lying down to standing up. 

“With long-COVID patients, it often has to be symptom-titrated exercise,” said Dr. Schamess. This means physical activity needs to be constantly monitored and adjusted on the basis of a patient’s symptoms. “We need to figure out what they can do that doesn’t provoke their symptoms,” he explained. 

Dr. Schamess often recommends that patients with long COVID, at least initially, focus on exercises in which they are sitting (such as cycling) or prone. 

“The key thing is most people with long COVID can do a lot more exercise in a sitting or lying position than a standing position,” he said. “It’s baffling to them that they can’t walk two blocks but can bike 10 miles.” 

For symptoms like fatigue or postexertional malaise, Dr. Schamess often refers patients to physical therapy to develop an individualized exercise program. A 2022 study published in Scandinavian Journal of Medicine & Science in Sports found that when long-COVID patients completed an 8-week program of three exercise sessions per week, they experienced significant improvements in quality of life, fatigue, muscle strength, and overall fitness compared with a control group. 

“It’s important to make sure that workouts are supervised, so that they can be modified as necessary” said Dr. Schamess. 

4. Take steps to improve sleep quality.

A 2023 study published in the Journal of General Internal Medicine found that about 40% of people with long COVID report sleep issues such as insomnia or not feeling refreshed in the morning. 

“Sleep may become challenging, which can be frustrating for a patient with long COVID who desperately needs rest,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center in New York City.

Some of the simplest ways to improve sleep are common sense; however, these issues never affected the person pre-COVID, so they have to become new habits.

“A lot of my patients with long COVID find that they are more sensitive to caffeine, so they really can’t have it anymore later in the day,” he said. “The same goes for bright screens” such as those on cell phones, tablets, and e-book readers, he said. “They may find that it’s harder for them to fall and stay asleep if they’re on their iPhone right before bed. These are all things that may not have been issues before they were diagnosed with long COVID.”

Dr. Purpura also said that he encourages his patients to practice mindfulness or relaxation exercises before bed, such as deep breathing. One technique he recommends is called box breathing, where the patient inhales for 4 seconds, holds his or her breath for 4 seconds, exhales for 4 seconds, then holds his or her breath again for 4 seconds. Some research suggests that this paced breathing technique, when done for 20 minutes before bed, helps to improve symptoms of insomnia. 

While sleep medications such as zolpidem (Ambien) are often used as short-term relief for insomnia, Dr. Schamess said he has not found them particularly helpful for sleep issues that stem from long COVID. 

“They help patients fall asleep but not necessarily stay asleep, which can be an issue for people with long COVID,” he said.

 

 

5. Consider medications.

No standard drugs or treatments have yet been approved to treat long COVID (although some, such as Paxlovid, are in clinical trials). But some medications may help to relieve symptoms, said Dr. Ganesh. These include:

  • Blood pressure drugs such as beta-blockers now used to treat POTS symptoms
  • Nerve-pain medications such as gabapentin or pregabalin. “These can also help with sleep, since patients don’t have pain to distract them,” said Dr. Ganesh.
  • Low-dose naltrexone to help with fatigue

“There’s not a one-size-fits-all approach to treat long-COVID symptoms,” said Dr. Ganesh. “You really need to work with the patient and possibly even cycle through several different medications before you find one that helps.”

A version of this article appeared on Medscape.com.

About 7% of US adults report having or having had symptoms of long COVID such as fatigue, heart palpitations and/or dizziness. These are 3 of the 12 symptoms identified as part of the National Institute of Health’s RECOVER initiative that can be reliably used to classify someone as having long COVID.

While there is no standard federally approved treatment for long COVID, physicians can recommend several strategies to their patients to help them recover.

The good news is that many people experience improvements in their symptoms over time by adopting these strategies, said Andrew Schamess, MD, an internal medicine physician at the Ohio State University Wexner Medical Center and director of its Post-COVID Recovery Program. 

1. Pace yourself.

Fatigue and postexertional malaise are 2 of the 12 symptoms used to classify someone as having long COVID. 

“There’s mental, or cognitive, fatigue, where people become exhausted after any span of time trying to do complicated cognitive tasks,” said Dr. Schamess. “There’s also general fatigue, or sleepiness, where after a few hours you feel like you could go right back to sleep.” 

The third category, he added, is postexertional malaise, where patients are exhausted by exercise, either immediately or up to 24-48 hours later.

That’s where a technique known as “pacing” can help. Pacing is an energy-conservation technique often used among people with other disabling conditions, such as chronic fatigue syndrome, said Ravindra Ganesh, MD, an internal medicine physician at the Mayo Clinic in Minnesota who specializes in long COVID.

“I tell patients that they have to figure out what their energy envelope is, which is the fixed amount of energy that they can use every day without crashing,” he said. 

You may be able to handle a daily 30-minute walk, for example, but if you pair it with something cognitively difficult, such as doing your taxes, your fatigue symptoms may flare up. 

“It’s hard advice for my patients to follow, as most are real go-getters,” he said. “But I point out to them that if they aim to minimize crashes, it will help them make slow progress.”

Over time, he said, their energy levels should gradually rise so that they can engage in more and more activity.

2. Follow a plant-based, anti-inflammatory diet.

There’s no research to suggest that following a certain eating pattern will help to reverse long COVID, said Dr. Ganesh. But in general, he said his patients anecdotally report that they feel better when they limit refined sugar and follow a plant-based diet that can help to lower inflammation in the body. 

“It makes sense, because it prevents dramatic blood glucose changes that can cause their body to crash,” he said. He generally recommends an anti-inflammatory diet like the Mediterranean diet, which is rich in fruits, vegetables, whole grains, and mono-unsaturated fat.

Many people with long COVID take an array of supplements, Dr. Ganesh said, although there’s little research to suggest that they may help. He does encourage patients to take about 2 g of an omega-3 supplement, such as fish oil, as it may help to reduce inflammation associated with long COVID

He also recommends fisetin, a dietary flavonoid found in fruits such as strawberries and kiwis. Preliminary research suggests that it may help to combat some of the neurologic damage associated with long COVID. 

“It appears to maintain mitochondrial function and has anti-inflammatory activities,” said Dr. Ganesh.

 

 

3. Modify exercise. 

Most of the time, exercise boosts health and reduces risk for certain diseases. But this strategy may not work for people who have certain symptoms from long COVID, such as postexertional malaise or postural orthostatic tachycardia syndrome (POTS), a condition that causes symptoms such as a fast heart rate, dizziness, and fatigue when transitioning from lying down to standing up. 

“With long-COVID patients, it often has to be symptom-titrated exercise,” said Dr. Schamess. This means physical activity needs to be constantly monitored and adjusted on the basis of a patient’s symptoms. “We need to figure out what they can do that doesn’t provoke their symptoms,” he explained. 

Dr. Schamess often recommends that patients with long COVID, at least initially, focus on exercises in which they are sitting (such as cycling) or prone. 

“The key thing is most people with long COVID can do a lot more exercise in a sitting or lying position than a standing position,” he said. “It’s baffling to them that they can’t walk two blocks but can bike 10 miles.” 

For symptoms like fatigue or postexertional malaise, Dr. Schamess often refers patients to physical therapy to develop an individualized exercise program. A 2022 study published in Scandinavian Journal of Medicine & Science in Sports found that when long-COVID patients completed an 8-week program of three exercise sessions per week, they experienced significant improvements in quality of life, fatigue, muscle strength, and overall fitness compared with a control group. 

“It’s important to make sure that workouts are supervised, so that they can be modified as necessary” said Dr. Schamess. 

4. Take steps to improve sleep quality.

A 2023 study published in the Journal of General Internal Medicine found that about 40% of people with long COVID report sleep issues such as insomnia or not feeling refreshed in the morning. 

“Sleep may become challenging, which can be frustrating for a patient with long COVID who desperately needs rest,” said Lawrence Purpura, MD, an infectious disease specialist and director of the long COVID clinic at Columbia University Medical Center in New York City.

Some of the simplest ways to improve sleep are common sense; however, these issues never affected the person pre-COVID, so they have to become new habits.

“A lot of my patients with long COVID find that they are more sensitive to caffeine, so they really can’t have it anymore later in the day,” he said. “The same goes for bright screens” such as those on cell phones, tablets, and e-book readers, he said. “They may find that it’s harder for them to fall and stay asleep if they’re on their iPhone right before bed. These are all things that may not have been issues before they were diagnosed with long COVID.”

Dr. Purpura also said that he encourages his patients to practice mindfulness or relaxation exercises before bed, such as deep breathing. One technique he recommends is called box breathing, where the patient inhales for 4 seconds, holds his or her breath for 4 seconds, exhales for 4 seconds, then holds his or her breath again for 4 seconds. Some research suggests that this paced breathing technique, when done for 20 minutes before bed, helps to improve symptoms of insomnia. 

While sleep medications such as zolpidem (Ambien) are often used as short-term relief for insomnia, Dr. Schamess said he has not found them particularly helpful for sleep issues that stem from long COVID. 

“They help patients fall asleep but not necessarily stay asleep, which can be an issue for people with long COVID,” he said.

 

 

5. Consider medications.

No standard drugs or treatments have yet been approved to treat long COVID (although some, such as Paxlovid, are in clinical trials). But some medications may help to relieve symptoms, said Dr. Ganesh. These include:

  • Blood pressure drugs such as beta-blockers now used to treat POTS symptoms
  • Nerve-pain medications such as gabapentin or pregabalin. “These can also help with sleep, since patients don’t have pain to distract them,” said Dr. Ganesh.
  • Low-dose naltrexone to help with fatigue

“There’s not a one-size-fits-all approach to treat long-COVID symptoms,” said Dr. Ganesh. “You really need to work with the patient and possibly even cycle through several different medications before you find one that helps.”

A version of this article appeared on Medscape.com.

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Cognitive Deficits After Most Severe COVID Cases Associated With 9-Point IQ Drop

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Thu, 03/14/2024 - 16:30

A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

 

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

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A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

 

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

A new study from the United Kingdom provides greater clarity on how SARS-CoV-2 infection can affect cognition and memory, including novel data on how long brain fog may last after the illness resolves and which cognitive functions are most vulnerable. 

In a large community sample, researchers found that on average, people who had recovered from COVID-19 showed small cognitive deficits equivalent to a 3-point loss in IQ for up to 1 year or more after recovering from the acute illness compared with peers who never had COVID-19.

However, people who had more severe cases, requiring treatment in a hospital intensive care unit, had cognitive deficits equivalent to a 9-point drop in IQ.

“People with ongoing persistent symptoms, indicative of long COVID, had larger cognitive deficits than people whose symptoms had resolved,” first author Adam Hampshire, PhD, with Imperial College London, London, England, told this news organization. 

The largest deficits among cognitive tasks were in memory, reasoning, and executive function, he added.

“That is, people who had had COVID-19 were both slower and less accurate when performing tasks that measure those abilities,” Dr. Hampshire said. “The group with the largest cognitive deficits were patients who had been in intensive care for COVID-19.”

The study was published online in The New England Journal of Medicine
 

Lingering Brain Fog

Cognitive symptoms after SARS-CoV-2 infection are well recognized, but whether objectively measurable cognitive deficits exist and how long they persist remains unclear. 

To investigate, researchers invited 800,000 adults from the REACT study of SARS-CoV-2 transmission in England to complete an online assessment for cognitive function with eight domains.

Altogether, 141,583 participants started the cognitive battery by completing at least one task, and 112,964 completed all eight tasks.

The researchers estimated global cognitive scores among participants who had been previously infected with SARS-CoV-2 with symptoms that persisted for at least 12 weeks, whether or not resolved, and among uninfected participants. 

Compared with uninfected adults, those who had COVID-19 that resolved had a small cognitive deficit, corresponding to a 3-point loss in IQ, the researchers found. 

Adults with unresolved persistent COVID-19 symptoms had the equivalent of a 6-point loss in IQ, and those who had been admitted to the intensive care unit had the equivalent of a 9-point loss in IQ, in line with previous findings of cognitive deficits in patients hospitalized in a critical care unit, the researchers report. 

Larger cognitive deficits were evident in adults infected early in the pandemic by the original SARS-CoV-2 virus or the B.1.1.7 variant, whereas peers infected later in the pandemic (eg., in the Omicron period), showed smaller cognitive deficits. This finding is in line with other studies suggesting that the association between COVID-19–associated cognitive deficits attenuated as the pandemic progressed, the researchers noted. 

They also found that people who had COVID-19 after receiving two or more vaccinations showed better cognitive performance compared with those who had not been vaccinated. 

The memory, reasoning, and executive function tasks were among the most sensitive to COVID-19–related cognitive differences and performance on these tasks differed according to illness duration and hospitalization. 

Dr. Hampshire said that more research is needed to determine whether the cognitive deficits resolve with time. 

“The implications of longer-term persistence of cognitive deficits and their clinical relevance remain unclear and warrant ongoing surveillance,” he said.

 

 

 

Larger Cognitive Deficits Likely?

These results are “a concern and the broader implications require evaluation,” wrote Ziyad Al-Aly, MD, with Washington University School of Medicine in St. Louis, Missouri, and Clifford Rosen, MD, with Tufts University School of Medicine in Boston, Massachusetts, in an accompanying editorial

In their view, several outstanding questions remain, including what the potential functional implications of a 3-point loss in IQ may be and whether COVID-19–related cognitive deficits predispose to a higher risk for dementia later in life. 

“A deeper understanding of the biology of cognitive dysfunction after SARS-CoV-2 infection and how best to prevent and treat it are critical for addressing the needs of affected persons and preserving the cognitive health of populations,” Drs. Al-Aly and Rosen concluded. 

Commenting on the study for this news organization, Jacqueline Becker, PhD, clinical neuropsychologist and assistant professor of medicine, Icahn School of Medicine at Mount Sinai, New York City, noted that “one important caveat” is that the study used an online assessment tool for cognitive function and therefore the findings should be taken with “a grain of salt.”

“That said, this is a large sample, and the findings are generally consistent with what we’ve seen in terms of cognitive deficits post-COVID,” Dr. Becker said. 

It’s likely that this study “underestimates” the degree of cognitive deficits that would be seen on validated neuropsychological tests, she added.

In a recent study, Dr. Becker and her colleagues investigated rates of cognitive impairment in 740 COVID-19 patients who recovered and were treated in outpatient, emergency department, or inpatient hospital settings. 

Using validated neuropsychological measures, they found a relatively high frequency of cognitive impairment several months after patients contracted COVID-19. Impairments in executive functioning, processing speed, category fluency, memory encoding, and recall were predominant among hospitalized patients. 

Dr. Becker noted that in her experience, cognition typically will improve in some patients 12-18 months post COVID. 

Support for the study was provided by the National Institute for Health and Care Research and UK Research and Innovation and by the Department of Health and Social Care in England and the Huo Family Foundation. Disclosures for authors and editorial writers are available at NEJM.org. Dr. Becker has no relevant disclosures.

A version of this article appeared on Medscape.com.

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COVID Virus Can Remain in the Body Over a Year

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Thu, 03/21/2024 - 09:51

Scientists at the University of California, San Francisco, have discovered that remnants of the COVID-19 virus can linger in blood and tissue for more than a year after a person is first infected.

In their research on long COVID, the scientists found COVID antigens in the blood for up to 14 months after infection, and in tissue samples for more than 2 years after infection. 

“These two studies provide some of the strongest evidence so far that COVID antigens can persist in some people, even though we think they have normal immune responses,” Michael Peluso, MD, an infectious disease researcher in the UCSF School of Medicine, who led both studies, said in a statement. 

Scientists don’t know what causes long COVID, in which symptoms of the illness persist months or years after recovery. The most common symptoms are extreme fatigue, shortness of breath, loss of smell, and muscle aches.

The UCSF research team examined blood samples from 171 infected people and found the COVID “spike” protein was still present up to 14 months after infection in some people. The antigens were found more often in people who were hospitalized with COVID or who reported being very sick but were not hospitalized.

Researchers next looked at the UCSF Long COVID Tissue Bank, which contains samples donated by patients with and without long COVID. 

They found portions of viral RNA in the tissue up to 2 years after people were infected, though there was no evidence of reinfection. Those viral fragments were found in connective tissue where immune cells are, suggesting that the fragments caused the immune system to attack, according to the researchers. 

The UCSF team is running clinical trials to find out if monoclonal antibodies or antiviral drugs can remove the virus. 

The findings were presented in Denver this week at the Conference on Retroviruses and Opportunistic Infections.

A version of this article appeared on WebMD.com.

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Scientists at the University of California, San Francisco, have discovered that remnants of the COVID-19 virus can linger in blood and tissue for more than a year after a person is first infected.

In their research on long COVID, the scientists found COVID antigens in the blood for up to 14 months after infection, and in tissue samples for more than 2 years after infection. 

“These two studies provide some of the strongest evidence so far that COVID antigens can persist in some people, even though we think they have normal immune responses,” Michael Peluso, MD, an infectious disease researcher in the UCSF School of Medicine, who led both studies, said in a statement. 

Scientists don’t know what causes long COVID, in which symptoms of the illness persist months or years after recovery. The most common symptoms are extreme fatigue, shortness of breath, loss of smell, and muscle aches.

The UCSF research team examined blood samples from 171 infected people and found the COVID “spike” protein was still present up to 14 months after infection in some people. The antigens were found more often in people who were hospitalized with COVID or who reported being very sick but were not hospitalized.

Researchers next looked at the UCSF Long COVID Tissue Bank, which contains samples donated by patients with and without long COVID. 

They found portions of viral RNA in the tissue up to 2 years after people were infected, though there was no evidence of reinfection. Those viral fragments were found in connective tissue where immune cells are, suggesting that the fragments caused the immune system to attack, according to the researchers. 

The UCSF team is running clinical trials to find out if monoclonal antibodies or antiviral drugs can remove the virus. 

The findings were presented in Denver this week at the Conference on Retroviruses and Opportunistic Infections.

A version of this article appeared on WebMD.com.

Scientists at the University of California, San Francisco, have discovered that remnants of the COVID-19 virus can linger in blood and tissue for more than a year after a person is first infected.

In their research on long COVID, the scientists found COVID antigens in the blood for up to 14 months after infection, and in tissue samples for more than 2 years after infection. 

“These two studies provide some of the strongest evidence so far that COVID antigens can persist in some people, even though we think they have normal immune responses,” Michael Peluso, MD, an infectious disease researcher in the UCSF School of Medicine, who led both studies, said in a statement. 

Scientists don’t know what causes long COVID, in which symptoms of the illness persist months or years after recovery. The most common symptoms are extreme fatigue, shortness of breath, loss of smell, and muscle aches.

The UCSF research team examined blood samples from 171 infected people and found the COVID “spike” protein was still present up to 14 months after infection in some people. The antigens were found more often in people who were hospitalized with COVID or who reported being very sick but were not hospitalized.

Researchers next looked at the UCSF Long COVID Tissue Bank, which contains samples donated by patients with and without long COVID. 

They found portions of viral RNA in the tissue up to 2 years after people were infected, though there was no evidence of reinfection. Those viral fragments were found in connective tissue where immune cells are, suggesting that the fragments caused the immune system to attack, according to the researchers. 

The UCSF team is running clinical trials to find out if monoclonal antibodies or antiviral drugs can remove the virus. 

The findings were presented in Denver this week at the Conference on Retroviruses and Opportunistic Infections.

A version of this article appeared on WebMD.com.

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5 Interesting Neurology Studies

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Fri, 03/01/2024 - 16:25

This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

 

 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

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This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

 

 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Dear colleagues, I’m Christoph Diener from the medical faculty of University Duisburg-Essen in Germany. Today I would like to tell you about five interesting studies that were published in January 2024.
 

Long COVID

I would like to start with long COVID. There is an ongoing discussion about whether this condition — which means symptoms like dizziness, vertigo, fatigue, headache, and cognitive impairment that persist for more than 6 months — is either a consequence of the infection, functional symptoms, psychosomatic disease, or a depression.

There is an important paper that came out in Science. The group investigated 39 controls and 113 patients who had COVID-19. At 6 months, 40 of them had long COVID. The researchers repeatedly measured more than 6500 proteins in serum. The patients with long COVID had a significant increase in complement activation, which persisted even beyond 6 months. These patients also showed increased tissue lesion markers in the blood and activation of the endothelium.

Also, they had increased platelet activation and autoantibodies with increased anti-cytomegalovirus and anti-Epstein-Barr virus immunoglobulins. These are very strong indicators that COVID-19 leads to long-term changes in our immune system, and different activations of complement factors could explain the variety of symptoms that these patients display. Whether this has consequences for treatment is unclear at the moment.
 

Parkinson’s Classification

Let me come to another issue, which is the future treatment of Parkinson’s disease, covered in a paper in The Lancet Neurology. I think you are all aware that once patients display symptoms like rigidity, bradykinesia, or tremor, it’s most probably too late for neuroprotective therapy because 70% of the dopaminergic neurons are already dead.

The authors propose a new biological diagnosis of the disease in the preclinical state. This early preclinical diagnosis has three components. One is to show the presence of synuclein either in skin biopsy or in serum. The second is proof of neurodegeneration either by MRI or by PET imaging. The third involves genetic markers.

On top of this, we know that we have preclinical manifestations of Parkinson’s disease, like REM sleep disorders, autonomic disturbances, and cognitive impairment. With this new classification, we should be able to identify the preclinical phase of Parkinson’s disease and include these patients in future trials for neuroprotection.
 

Niemann-Pick Disease

My third study, in The New England Journal of Medicine, deals with Niemann-Pick disease type C (Trial of N-Acetyl-l-Leucine in Niemann–Pick Disease Type C. This is a rare autosomal recessive disorder that involves impaired lysosomal storage. This disease, which manifests usually in childhood, goes along with systemic, psychiatric, and neurologic abnormalities, and in particular, ataxia. Until now, there has been only one therapy, with miglustat. which has many side effects.

The group of authors found a new therapeutic approach with N-acetyl-L-leucine, which primarily increases mitochondrial energy production. This was a small, placebo-controlled, crossover trial with 2 x 12 weeks of treatment. This new compound showed efficacy and was very well tolerated. This shows that we definitely need long-term studies with this new, well-tolerated drug in this rare disease.
 

 

 

Anticoagulation in Subclinical AF

My fourth study comes from the stroke-prevention field, published in The New England Journal of Medicine. I think you are aware of subclinical atrail fibrillation. These are high-frequency episodes in ECG, usually identified by pacemakers or ECG monitoring systems. The international ARTESIA study included more than 4000 patients randomized either to apixaban 5 mg twice daily or aspirin 81 mg.

After 3.5 years, the investigators showed a small but significant decrease in the rate of stroke, with a relative risk reduction of 37%, but also, unfortunately, a significantly increased risk for major bleeding with apixaban. This means that we need a careful discussion with the patient, the family, and the GP to decide whether these patients should be anticoagulated or not.
 

Migraine and Depression

My final study, published in the European Journal of Neurology, deals with the comorbidity of depression and migraine. This study in the Netherlands included 108 patients treated with erenumab and 90 with fremanezumab; 68 were controls.

They used two depression scales. They showed that treatment with the monoclonal antibodies improved at least one of the two depression scales. I think this is an important study because it indicates that you can improve comorbid depression in people with severe migraine, even if this study did not show a correlation between the reduction in monthly migraine days and the improvement of depression.

What we learned for clinical practice is that we have to identify depression in people with migraine and we have to deal with it. Whether it’s with the treatment of monoclonal antibodies or antidepressant therapy doesn’t really matter.

Dear colleagues, we had interesting studies this month. I think the most spectacular one was published in Science on long COVID. Thank you very much for listening and watching. I’m Christoph Diener from University Duisburg-Essen.
 

Dr. Diener is Professor, Department of Neurology, Stroke Center-Headache Center, University Duisburg-Essen, Essen, Germany. He disclosed ties with Abbott; Addex Pharma; Alder; Allergan; Almirall; Amgen; Autonomic Technology; AstraZeneca; Bayer Vital; Berlin Chemie; Bristol-Myers Squibb; Boehringer Ingelheim; Chordate; CoAxia; Corimmun; Covidien; Coherex; CoLucid; Daiichi-Sankyo; D-Pharml Electrocore; Fresenius; GlaxoSmithKline; Grunenthal; Janssen-Cilag; Labrys Biologics Lilly; La Roche; 3M Medica; MSD; Medtronic; Menarini; MindFrame; Minster; Neuroscore; Neurobiological Technologies; Novartis; Novo-Nordisk; Johnson & Johnson; Knoll; Paion; Parke-Davis; Pierre Fabre; Pfizer Inc; Schaper and Brummer; sanofi-aventis; Schering-Plough; Servier; Solvay; Syngis; St. Jude; Talecris; Thrombogenics; WebMD Global; Weber and Weber; Wyeth; and Yamanouchi.

A version of this article appeared on Medscape.com.

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Biological Sex Differences: Key to Understanding Long COVID?

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Fri, 03/01/2024 - 11:14

Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

 

 

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

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Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

 

 

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

Letícia Soares was infected with COVID-19 in April 2020, in the final year of postdoctoral studies in disease ecology at a Canadian University. What started with piercing migraines and severe fatigue in 2020 soon spiraled into a myriad of long COVID symptoms: Gastrointestinal issues, sleep problems, joint and muscle pain, along with unexpected menstrual changes.

After an absence of menstrual bleeding and its usual signs, she later suffered from severe periods and symptoms that worsened her long COVID condition. “It just baffled me,” said Soares, now 39. “It was debilitating.”

Cases like Soares’s are leading scientists to spend more time trying to understand the biological sex disparity in chronic illnesses such as long COVID that until recently have all but been ignored. According to the Centers for Disease Control and Prevention, long COVID affects nearly twice as many women as men.

What’s more, up to two thirds of female patients with long COVID report an increase in symptoms related to menstruation, which suggests a possible link between sex hormone fluctuations and immune dysfunction in the illness.

“These illnesses are underfunded and understudied relative to their disease burdens,” said Beth Pollack, a research scientist at the Massachusetts Institute of Technology, Cambridge, Massachusetts, who studies complex chronic illnesses.

Addressing knowledge gaps, especially around sex differences, could significantly improve our understanding of complex chronic illnesses, said Pollack, who coauthored a 2023 literature review of female reproductive health impacts of long COVID.

Emerging ‘Menstrual Science’ Could Be Key

There is a critical need, she said, for studies on these illnesses to include considerations of sex differences, hormones, reproductive phases, and reproductive conditions. This research could potentially inform doctors and other clinicians or lead to treatments, both for reproductive symptoms and for the illnesses themselves.

Pollack noted that reproductive symptoms are prevalent across a group of infection-associated chronic illnesses she studies, all of which disproportionately affect women. These associated conditions, traditionally studied in isolation, share pathologies like reproductive health concerns, signaling a need for focused research on their shared mechanisms.

Recognizing this critical gap, “menstrual science” is emerging as a pivotal area of study, aiming to connect these dots through focused research on hormonal influences.

Researchers at the University of Melbourne, Melbourne, Australia, for example, are studying whether hormones play a role in causing or worsening the symptoms of long COVID. By comparing hormone levels in people with these conditions with those in healthy people and by tracking how symptoms change with hormone levels over time and across menstrual cycles, scientists hope to find patterns that could help diagnose these conditions more easily and lead to new treatments. They’re also examining how hormonal life phases such as puberty, pregnancy, or perimenopause and hormone treatments like birth control might affect these illnesses.

How Gender and Long COVID Intertwine

The pathologies of long COVID, affecting at least 65 million people worldwide, currently focus on four hypotheses: Persistent viral infection, reactivation of dormant viruses (such as common herpes viruses), inflammation-related damage to tissues and organs, and autoimmunity (the body attacking itself).

It’s this last reason that holds some of the most interesting clues on biological sex differences, said Akiko Iwasaki, PhD, a Yale University, New Haven, Connecticut, immunologist who has led numerous research breakthroughs on long COVID since the start of the pandemic. Women have two X chromosomes, for example, and although one is inactivated, the inactivation is incomplete.

Some cells still express genes from the “inactivated genes” on the X chromosome, Iwasaki said. Those include key immune genes, which trigger a more robust response to infections and vaccinations but also predispose them to autoimmune reactions. “It comes at the cost of triggering too much immune response,” Iwasaki said.

Sex hormones also factor in. Testosterone, which is higher in males, is immunosuppressive, so it can dampen immune responses, Iwasaki said. That may contribute to making males more likely to get severe acute infections of COVID-19 but have fewer long-term effects.

Estrogen, on the other hand, is known to enhance the immune response. It can increase the production of antibodies and the activation of T cells, which are critical for fighting off infections. This heightened immune response, however, might also contribute to the persistent inflammation observed in long COVID, where the immune system continues to react even after the acute infection has resolved.

 

 

Sex-Specific Symptoms and Marginalized Communities

Of the more than 200 symptoms long haulers experience, Iwasaki said, several are also sex-specific. A recent draft study by Iwasaki and another leading COVID researcher, David Putrino, PhD, at Mount Sinai Health System in New York City, shows hair loss as one of the most female-dominant symptoms and sexual dysfunction among males.

In examining sex differences, another question is why long COVID rates in the trans community are disproportionately high. One of the reasons Iwasaki’s lab is looking at testosterone closely is because anecdotal evidence from female-to-male trans individuals indicates that testosterone therapy improved their long COVID symptoms significantly. It also raises the possibility that hormone therapy could help.

However, patients and advocates say it’s also important to consider socioeconomic factors in the trans community. “We need to start at this population and social structure level to understand why trans people over and over are put in harm’s way,” said JD Davids, a trans patient-researcher with long COVID and the cofounder and codirector of Strategies for High Impact and its Long COVID Justice project.

For trans people, said Davids, risk factors for both severe COVID and long COVID include being part of low-income groups, belonging to marginalized racial and ethnic communities, and living in crowded environments such as shelters or prisons.

The disproportionate impact of long COVID on marginalized communities, especially when seen through the lens of historical medical neglect, also demands attention, said Iwasaki. “Women used to be labeled hysteric when they complained about these kinds of symptoms.”

Where It All Leads

The possibility of diagnosing long COVID with a simple blood test could radically change some doctors’ false perceptions that it is not a real condition, Iwasaki said, ensuring it is recognized and treated with the seriousness it deserves.

“I feel like we need to get there with long COVID. If we can order a blood test and say somebody has a long COVID because of these values, then suddenly the diseases become medically explainable,” Iwasaki added. This advancement is critical for propelling research forward, she said, refining treatment approaches — including those that target sex-specific hormone, immunity, and inflammation issues — and improving the well-being of those living with long COVID.

This hope resonates with scientists like Pollack, who recently led the first National Institutes of Health-sponsored research webinar on less studied pathologies in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID, and with the experiences of individuals like Soares, who navigates through the unpredictable nature of both of these conditions with resilience.

“This illness never ceases to surprise me in how it changes my body. I feel like it’s a constant adaptation,” said Soares. Now living in Salvador, Brazil, her daily life has dramatically shifted to the confines of her home.

“It’s how I have more predictability in my symptoms,” she said, pointing out the pressing need for the scientific advancements that Iwasaki envisions and a deepening of our understanding of the disease’s impacts on patients’ lives.

A version of this article appeared on Medscape.com.

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Vaccinated People Have Up to 58% Lower Risk of Long COVID

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Fri, 02/23/2024 - 12:22

People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

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People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

People vaccinated against COVID-19 were significantly less likely to have long COVID during the first few years of the pandemic, a new study from Michigan shows.

The findings were published in the journal Annals of Epidemiology. Researchers analyzed data for 4695 adults in Michigan, looking for people reporting COVID symptoms for more than 30 or more than 90 days after infection. They then looked at whether people had completed a full, initial vaccination series or not. Vaccinated people were 58% less likely than unvaccinated people to have symptoms lasting at least 30 days, and they were 43% less likely to have symptoms for 90 days or more.

The researchers did their study because previous estimates of how much vaccination protects against long COVID have varied widely due to different ways of doing the research, such as mixed definitions of long COVID or including a limited set of people in the unvaccinated comparison group. The researchers wrote that their study offers more certainty because the people who took part in it more widely represent the general population. All of the people in the study had lab test-confirmed infections of SARS-CoV-2 (the virus that causes COVID) between March 2020 and May 2022.

Among vaccinated and unvaccinated people combined, 32% of infected people said they had symptoms for at least 30 days, and nearly 18% said they had symptoms for 90 days or more, according to a summary of the study published by the Center for Infectious Disease Research and Policy at the University of Minnesota. The researchers compared vaccinated and unvaccinated people multiple ways and consistently showed at least a 40% difference in long COVID.

In 2022, 6.9% of US adults self-reported that they had had long COVID, which researchers defined as symptoms for at least 3 months after testing positive or being diagnosed by a doctor, according to a report last week from the CDC. That report also showed that the states with the highest rates of long COVID in 2022 were Alabama, Montana, North Dakota, Oklahoma, Tennessee, West Virginia, and Wyoming. West Virginia had the highest rate of self-reported long COVID, at 10.6% of adults.

People with long COVID may have one or more of about 20 symptoms, including tiredness, fever, and problems that get worse after physical or mental effort. Other long-term signs are respiratory and heart symptoms, thinking problems, digestive issues, joint or muscle pain, rashes, or changes in menstrual cycles. The problems can be so severe that people may qualify for disability status.

About 8 in 10 US adults got the initial round of COVID vaccines, but just 22% of people reported receiving the latest version that became available in the fall of 2023.

The authors of the Michigan study wrote that “COVID-19 vaccination may be an important tool to reduce the burden of long COVID.”

A version of this article appeared on WebMD.com.

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Study IDs Immune Abnormality Possibly Causing Long COVID

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Fri, 02/23/2024 - 11:39

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

 

 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

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Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

 

 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

Swiss scientists have identified immune system abnormalities in patients with long COVID that might open the door to new diagnostic tests and treatments.

The researchers found that a group of proteins in the blood that are part of the body’s immune response called the “complement system” are not working properly in patients with long COVID.

Blood samples turned up important differences between those who recovered from COVID and those who did not. These differences might be used as biomarkers to diagnose long COVID and might even point the way to new treatments for the condition, the researchers said.

By testing for 6500 blood proteins in about 300 patients, the Swiss researchers found that dysfunctional complement system proteins could possibly explain fatigue and “smoldering inflammation,” said Onur Boyman, MD, a professor of immunology from University Hospital Zurich in Zurich, Switzerland.

Long COVID has been linked to hundreds of symptoms including brain fog, chronic fatigue, pain, and digestive issues. Various factors drive the condition and likely work with one another other, said David Putrino, PhD, from the Icahn School of Medicine at Mount Sinai in New York City. The Swiss study is useful because “we’re trying to best understand how we can explain all of this far-reaching pathobiology,” he said.
 

Testing Across Continents

Dr. Boyman’s team collected blood samples from people with COVID in Europe and New York and tracked them. They compared those who developed long COVID with those who did not. One protein that was most unique to patients with long COVID is a blood complement that activates the immune system, Dr. Boyman said. But in people with long COVID, the immune response stays activated after the virus is gone. He described the response as “smoldering inflammation” in multiple organs, including the lungs and the gastrointestinal system.

The complement system also plays a role in clearing the body of dead cells. If the cells “lie around too much,” they can trigger an immune response, he said.

That may explain exercise intolerance in people with long COVID, Dr. Boyman said. Some people with long COVID have inflammation in the epithelium — the inner layer of their blood vessels. This would make it harder for the circulatory systems to recover from exercise, Dr. Boyman said.

“We think this regulated complement system is actually quite a central piece of the puzzle,” he said.
 

The Microclot Connection

The findings also support past research linking blood clots to long COVID. He suggested that clinicians and researchers consider testing drugs that regulate or inhibit the complementary system as a treatment of long COVID. Dr. Boyman said they are currently used for rare immune diseases.

Resia Pretorius, PhD, a professor of physiological sciences at Stellenbosch University in Stellenbosch, South Africa, said scientists studying the role of microclots in patients with long COVID often see complementary proteins inside the clots, so it has already been associated with long COVID. But she likened this clotting process to a garbage can that “just rolls along and collects everything that gets in its way. I think they are actively driving inflammation and disease.”

One factor complicating long COVID diagnosis and treatment is that it is a complex condition that involves multiple organ systems. That’s why the latest research suggests an underlying driver for the multiple symptoms of long COVID, Dr. Putrino said.

“Not every person has every symptom; not every person has every organ system affected,” Dr. Putrino said. “Whatever is happening is decided across the whole body.”
 

 

 

Research Offers New Direction

The Swiss paper contributes to the effort to identify systemic issues contributing to long COVID. It gives researchers one more thing to test for and link to specific, long COVID symptoms, opening the door to new treatments, Dr. Putrino said.

He doesn’t think the study supports treating the complement dysfunction if researchers don’t know what’s driving it. It may be complicated by the body’s failure to clear the virus completely, he said.

Dr. Pretorius recommended doctors test patients with long COVID for specific symptoms that may be treated using existing therapies. “If you think your patient had vascular pathology, you can test for it,” she said.

Some patients have found certain supplements and over-the-counter products helpful, she said. Among them: Coenzyme Q 10 and clot-busters such as streptokinase and Nattokinase (though she noted some doctors may not be comfortable with supplements).

“It’s the only thing we have until we’ve got trials,” she said.

Dr. Putrino said more research is needed to identify potential root causes and symptoms. A common refrain, but the only thing that will lead to specific treatments.

A version of this article appeared on Medscape.com.

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Virus and Booster Apathy Could Be Fueling Long COVID

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Changed
Wed, 02/21/2024 - 07:36

Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

 

 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

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Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

 

 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

 

 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

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Long COVID: Another Great Pretender

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Tue, 02/13/2024 - 13:03

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

 

 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

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

Publications
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Sections

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

 

 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

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

Has COVID replaced syphilis as the great imitator? At the turn of the 20th century, Sir William Osler was quoted as saying, “He who knows syphilis knows medicine.”

If you have any doubts about the “imitator” analogy, simply use any broad search engine or AI portal and enter “what is the differential diagnosis of primary syphilis, or secondary syphilis, or tertiary syphilis?” A plethora of diseases across many body systems appears.
 

Another Great Pretender?

Did you or do you now have long COVID? How do you know? Do you even know what long COVID is? How would you diagnosis it?

When asked about long COVID, this is what large language model source bard.google.com had to say:

Long COVID, also known as post-COVID conditions or PASC, is a complex condition that can occur in people who have had COVID-19, even if their initial illness was mild or even asymptomatic. It’s characterized by a wide range of symptoms that can last for weeks, months, or even years after the initial infection.

Symptoms of long COVID can include: fatigue, shortness of breath, brain fog (trouble thinking or concentrating), loss of smell or taste, sleep problems, muscle pain, joint pain, headache, dizziness, depression or anxiety, heart palpitations, gastrointestinal problems.

Duh!!! It reads much like a continuation of the symptoms of acute COVID. Bard continued:

The exact cause of long COVID is still unknown, but there are several theories. One possibility is that the virus itself can damage organs and tissues, leading to ongoing symptoms. Another possibility is that the immune system’s response to the virus can continue to cause inflammation even after the virus is gone.

Human intelligence source Wikipedia says this:

Long COVID or long-haul COVID is a group of health problems persisting or developing after an initial COVID-19 infection. Symptoms can last weeks, months or years and are often debilitating. The World Health Organization defines long COVID as starting three months after infection, but other definitions put the start of long COVID at four weeks.

Highly varied, including post-exertional malaise (symptoms made worse with effort), fatigue, muscle pain, shortness of breath, chest pain, and cognitive dysfunction (brain fog).
 

Acute COVID to Long COVID

The World Health Organization estimates that 36 million people in the European region have developed long COVID in the first 3 years of the pandemic. That›s a lot.

We all know that the common signs and symptoms of acute COVID-19 include fever or chills, a dry cough and shortness of breath, feeling very tired, muscle or body aches, headache, loss of taste or smell, sore throat, congestion, runny nose, nausea, vomiting, and diarrhea. Except for the taste and smell findings, every one of these symptoms or signs could indicate a different virus infection or even some type of allergy. My point is the nonspecificity in this list.

Uncommon signs and symptoms of acute COVID include a flat skin rash covered with small bumps, discolored swollen areas on the fingers and toes (COVID toes), and hives. The skin of hands, wrists, or ankles also can be affected. Blisters, itchiness, rough skin, or pus can be seen.

Severe confusion (delirium) might be the main or only symptom of COVID-19 in older people. This COVID-19 symptom is linked with a high risk for poor outcomes, including death. Pink eye (conjunctivitis) can be a COVID-19 symptom. Other eye problems linked to COVID-19 are light sensitivity, sore eyes, and itchy eyes. Acute myocarditis, tinnitus, vertigo, and hearing loss have been reported. And 1-4 weeks after the onset of COVID-19 infection, a patient may experience de novo reactive synovitis and arthritis of any joints.

So, take your pick. Myriad symptoms, signs, diseases, diagnoses, and organ systems — still present, recurring, just appearing, apparently de novo, or after asymptomatic infection. We have so much still to learn.

What big-time symptoms, signs, and major diseases are not on any of these lists? Obviously, cancer, atherosclerotic cardiovascular diseases, obesity, bone diseases, and competitive infections. But be patient; the lingering effects of direct tissue invasion by the virus as well as a wide range of immunologic reactions may just be getting started. Mitochondrial damage, especially in muscles, is increasingly a pathophysiologic suspect.

Human diseases can be physical or mental; and in COVID, that twain not only meet but mix and mingle freely, and may even merge into psychosoma. Don’t ever forget that. Consider “fatigue.” Who among us, COVID or NOVID, does not experience that from time to time?

Or consider brain fog as a common reported symptom of COVID. What on earth is that actually? How can a person know they have brain fog, or whether they had it and are over it?

We need one or more lab or other diagnostic tests that can objectively confirm the diagnosis of long COVID.
 

 

 

Useful Progress?

A recent research paper in Science reported intriguing chemical findings that seemed to point a finger at some form of complement dysregulation as a potential disease marker for long COVID. Unfortunately, some critics have pointed out that this entire study may be invalid or irrelevant because the New York cohort was recruited in 2020, before vaccines were available. The Zurich cohort was recruited up until April 2021, so some may have been vaccinated.

Then this news organization came along in early January 2024 with an article about COVID causing not only more than a million American deaths but also more than 5000 deaths from long COVID. We physicians don’t really know what long COVID even is, but we have to sign death certificates blaming thousands of deaths on it anyway? And rolling back the clock to 2020: Are patients dying from COVID or with COVID, according to death certificates?Now, armed with the knowledge that “documented serious post–COVID-19 conditions include cardiovascular, pulmonary, neurological, renal, endocrine, hematological, and gastrointestinal complications, as well as death,” CDC has published clear and fairly concise instructions on how to address post-acute COVID sequelae on death certificates.

In late January, this news organization painted a hopeful picture by naming four phenotypes of long COVID, suggesting that such divisions might further our understanding, including prognosis, and even therapy for this condition. Among the clinical phenotypes of (1) chronic fatigue–like syndrome, headache, and memory loss; (2) respiratory syndrome (which includes cough and difficulty breathing); (3) chronic pain; and (4) neurosensorial syndrome (which causes an altered sense of taste and smell), overlap is clearly possible but isn›t addressed.

I see these recent developments as needed and useful progress, but we are still left with…not much. So, when you tell me that you do or do not have long COVID, I will say to you, “How do you know?”

I also say: She/he/they who know COVID know medicine.

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

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