Long COVID

It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).

However, new research suggests that may be an underestimate and that far more people may be suffering from long COVID without ever having tested positive for the virus. Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.

“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.

He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.

Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.

“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.

The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.

Delayed care

The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.

They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.

They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.

“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.

The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.

However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.

Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.

Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
 

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

This article was updated 8/28/23.

It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).

However, new research suggests that may be an underestimate and that far more people may be suffering from long COVID without ever having tested positive for the virus. Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.

“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.

He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.

Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.

“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.

The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.

Delayed care

The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.

They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.

They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.

“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.

The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.

However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.

Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.

Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
 

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

This article was updated 8/28/23.

It’s been estimated that up to one-third of people who survive acute SARS-CoV-2 infection will suffer a post-viral syndrome with lingering neurologic and other symptoms – now known as long COVID or neurological postacute sequelae of SARS-CoV-2 infection (Neuro-PASC).

However, new research suggests that may be an underestimate and that far more people may be suffering from long COVID without ever having tested positive for the virus. Researchers found a significant proportion of patients in their small study who had never tested positive for COVID-19 but who were having symptoms of long COVID nevertheless showed evidence of immune responses consistent with previous exposure.

“We estimate that millions of people got COVID in the U.S. during the first year of the pandemic and then developed long COVID, yet they did not get a positive COVID diagnosis because of testing limitations,” Igor J. Koralnik, MD, of Northwestern Medicine Comprehensive COVID-19 Center in Chicago, said in an interview.

He noted that many post-COVID-19 clinics in the United States don’t accept people with long COVID symptoms who do not have a positive test result.

Patients with long COVID symptoms but without laboratory evidence of prior infection, “who have often been rejected and stigmatized, should feel vindicated by the results of our study,” Dr. Koralnik said.

“We think that those patients deserve the same clinical care as those with a positive test, as well as inclusion in research studies. This is what we are doing at Northwestern Medicine’s Comprehensive COVID[-19] Center,” Dr. Koralnik added.

The study was published online in the journal Neurology: Neuroimmunology & Neuroinflammation.

Delayed care

The researchers measured SARS-CoV-2-specific humoral and cell-mediated immune responses against nucleocapsid protein and spike proteins, which indicate a prior COVID-19 infection, in 29 patients with post-viral syndrome after suspected COVID-19, including neurologic symptoms such as cognitive impairment, headache, and fatigue, but who did not have a confirmed positive COVID-19 test.

They did the same in 32 age- and sex-matched COVID long haulers with confirmed Neuro-PASC and 18 healthy controls with none of the symptoms of long COVID and no known exposure to SARS-CoV-2 or positive test result.

They found that 12 of the 29 patients (41%) with post-viral syndrome (but no positive COVID-19 test) had detectable humoral and cellular immune responses consistent with prior exposure to SARS-CoV-2. Three-quarters harbored antinucleocapsid and 50% harbored antispike responses.

“Our data suggest that at least 4 million people with post-viral syndrome similar to long COVID may indeed have detectable immune responses to support a COVID diagnosis,” Dr. Koralnik said in a news release.

The 12 patients with post-viral syndrome but without a confirmed COVID-19 test had neurologic symptoms similar to those of patients with confirmed Neuro-PASC.

However, lack of a confirmed COVID-19 diagnosis likely contributed to the 5-month delay in the median time from symptom onset to clinic visit, the researchers said. They were evaluated at a median of 10.7 months vs. 5.4 months for Neuro-PASC patients.

Dr. Koralnik said in an interview that the “most important take-home message” of the study is that patients with post-viral syndrome often present with clinical manifestations similar to those of confirmed patients with Neuro-PASC, suggesting that a positive result by commercially available SARS-CoV-2 diagnostic test should not be a prerequisite for accessing care.

Patients with post-viral syndrome may benefit from the same clinical care as confirmed patients with Neuro-PASC, and the absence of a positive SARS-CoV-2 test should not preclude or delay treatment, he added.
 

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

This article was updated 8/28/23.

People who have been infected with the COVID-19 virus have a greater risk of many long-term health conditions, including diabetes, lung problems, fatigue, blood clots, and disorders affecting the gastrointestinal and musculoskeletal systems.

That is the finding of a new study from Washington University in St. Louis. The school distributed a press release about the study, which was published in the journal Nature Medicine.

“Some estimates show more than 90% of the U.S. population has been infected with COVID-19,” Ziyad Al-Aly, chief of research and development at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University, told the St. Louis Post–Dispatch. “Doctors need to realize that their patients could be at risk of these conditions, be it heart disease or lung problems or brain problems – they’re at risk.”

The researchers compared the health records for 138,000 patients who had been infected with those of 6 million who had not. They followed 80 health conditions associated with long COVID for 2 years. They used unnamed records from the VA.

“There was really nothing at all looking at what happens to people at two years after the infection,” Dr. Al-Aly said. “So we decided to take a look.”

Patients who hadn’t been hospitalized within 30 days of infection had a higher risk of death 6 months after recovery, and a higher risk of hospitalization within 18 months. They had higher risk of diabetes, fatigue, joint pain, and other problems compared with people who had not been infected.

“In the nonhospitalized group, risks remained elevated for several problems, for several organ systems,” Dr. Al-Aly said. “For the people who were hospitalized, the risk was ubiquitous across all organ systems. It really spans the gamut with respect to the organ systems that are affected.”

People who had been hospitalized had a 65% greater risk of illnesses after 2 years. Nonhospitalized patients had just a 35% greater risk.

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

People who have been infected with the COVID-19 virus have a greater risk of many long-term health conditions, including diabetes, lung problems, fatigue, blood clots, and disorders affecting the gastrointestinal and musculoskeletal systems.

That is the finding of a new study from Washington University in St. Louis. The school distributed a press release about the study, which was published in the journal Nature Medicine.

“Some estimates show more than 90% of the U.S. population has been infected with COVID-19,” Ziyad Al-Aly, chief of research and development at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University, told the St. Louis Post–Dispatch. “Doctors need to realize that their patients could be at risk of these conditions, be it heart disease or lung problems or brain problems – they’re at risk.”

The researchers compared the health records for 138,000 patients who had been infected with those of 6 million who had not. They followed 80 health conditions associated with long COVID for 2 years. They used unnamed records from the VA.

“There was really nothing at all looking at what happens to people at two years after the infection,” Dr. Al-Aly said. “So we decided to take a look.”

Patients who hadn’t been hospitalized within 30 days of infection had a higher risk of death 6 months after recovery, and a higher risk of hospitalization within 18 months. They had higher risk of diabetes, fatigue, joint pain, and other problems compared with people who had not been infected.

“In the nonhospitalized group, risks remained elevated for several problems, for several organ systems,” Dr. Al-Aly said. “For the people who were hospitalized, the risk was ubiquitous across all organ systems. It really spans the gamut with respect to the organ systems that are affected.”

People who had been hospitalized had a 65% greater risk of illnesses after 2 years. Nonhospitalized patients had just a 35% greater risk.

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

People who have been infected with the COVID-19 virus have a greater risk of many long-term health conditions, including diabetes, lung problems, fatigue, blood clots, and disorders affecting the gastrointestinal and musculoskeletal systems.

That is the finding of a new study from Washington University in St. Louis. The school distributed a press release about the study, which was published in the journal Nature Medicine.

“Some estimates show more than 90% of the U.S. population has been infected with COVID-19,” Ziyad Al-Aly, chief of research and development at Veterans Affairs St. Louis Health Care System and clinical epidemiologist at Washington University, told the St. Louis Post–Dispatch. “Doctors need to realize that their patients could be at risk of these conditions, be it heart disease or lung problems or brain problems – they’re at risk.”

The researchers compared the health records for 138,000 patients who had been infected with those of 6 million who had not. They followed 80 health conditions associated with long COVID for 2 years. They used unnamed records from the VA.

“There was really nothing at all looking at what happens to people at two years after the infection,” Dr. Al-Aly said. “So we decided to take a look.”

Patients who hadn’t been hospitalized within 30 days of infection had a higher risk of death 6 months after recovery, and a higher risk of hospitalization within 18 months. They had higher risk of diabetes, fatigue, joint pain, and other problems compared with people who had not been infected.

“In the nonhospitalized group, risks remained elevated for several problems, for several organ systems,” Dr. Al-Aly said. “For the people who were hospitalized, the risk was ubiquitous across all organ systems. It really spans the gamut with respect to the organ systems that are affected.”

People who had been hospitalized had a 65% greater risk of illnesses after 2 years. Nonhospitalized patients had just a 35% greater risk.

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

By now, concerns about COVID-related lawsuits have faded into the rear view mirror for most physicians.

But just when COVID lawsuits appear to be dwindling out, legal experts see a new lawsuit risk on the horizon – long COVID claims. While some say it’s doubtful the claims will succeed, the lawsuits could still create legal headaches for doctors in the form of time and money.

Long COVID claims are defined as complaints that allege that a diagnosis of long COVID was missed or delayed and that caused harm or injury. Lawsuits may also include claims in which patients allege that they were misdiagnosed as having long COVID when they were really suffering from another condition.

So far, a handful of long COVID claims have come down the pipeline, said Peter A. Kolbert, JD, senior vice president of claims and litigation services for Healthcare Risk Advisors, part of TDC Group.

“This is an area that is emerging as we speak,” Mr. Kolbert said. “We are starting to see these claims trickle in.”

In a recent case, for example, a patient sued her primary care physician for negligence, alleging her original SARS-CoV-2 infection was mismanaged and that this led to permanent neuropathy from long COVID. Had the patient been treated appropriately, the patient contends, she would not have developed long COVID or the resulting neuropathy, said Mr. Kolbert. An outcome in the case has not yet been reached, added Mr. Kolbert, who heard about the claim from a colleague.

The increase in the number of lawsuits raises concerns about how courts and juries might decide long COVID claims when so much about the condition is still unknown and best treatment practices are still developing. Research shows that long COVID occurs in at least 10% of cases of SARS-CoV-2 infection, and more than 200 symptoms have been identified. A Kaiser Family Foundation study found that 15% of the U.S. population believe they have experienced the symptoms of long COVID at some point, and 6% of people believe they currently have long COVID.

The risk of long COVID lawsuits underscores the importance of physicians taking proactive steps to protect themselves from liability when treating patients who might have the condition, say legal experts.

“There are legal standards that say new, unestablished scientific principles shouldn’t be first tested by a jury, they should be recognized and established within their [professional] area,” Mr. Kolbert said. “While we are seeing lawsuits related to long COVID, I think it is truly putting the cart before the horse, because there needs to be societal recognition that we’re still learning how to define and treat long COVID.”
 

What are patients alleging?

In the few long COVID claims that have arisen, some complaints have alleged delay in the recognition and treatment of long COVID, according to Mr. Kolbert. There have also been claims that physicians failed to refer a patient with long COVID to a specialist in a timely way and that this results in the patient’s experiencing chronic fatigue or a neuropathy.

Fatigue is one of the most common symptoms associated with long COVID, according to recent studies. Other symptoms include postexertional malaise, brain fog, and gastrointestinal problems.

Another rising legal theme is failure to adequately communicate with patients about what long COVID is and what it entails.

Whether plaintiffs who bring long COVID claims will be successful in court remains a question.

Andrew D. DeSimone, JD, a Lexington, Ky.–based medical malpractice defense attorney, said he has not seen any claims involving long COVID. He added that a long COVID claim would be challenging to prove, considering the standard of care for treating the condition is still evolving. Plaintiffs in a medical malpractice action must prove that physicians owed a duty of care to the patient, that the doctor breached that duty by failing to conform to the standard of care, and that the breach caused an injury that harmed the patient.

Mr. DeSimone also doubts whether juries would be very sympathetic to such plaintiffs.

“There’s a lot of fatigue around COVID still,” he said. “I don’t know if a jury would buy into someone claiming long COVID. I think the claim would have a hard time gaining traction. Not that it’s impossible.”

Another unanswered question is whether legal protections enacted by states during the pandemic might apply to long COVID claims.

Shortly after the pandemic started, most states enacted laws or executive orders that shielded physicians from liability claims relating to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proved. The U.S. Department of Health and Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19.

Some of these state immunities have since expired. Other states have extended their legal protections for short periods. In Indiana, for example, physicians and businesses are protected until Dec. 31, 2024, from civil tort actions that allege damages arising from COVID-19.

It’s possible that in long COVID lawsuits, physicians would be protected by the immunities unless the cases come after the protections expire, said J. Richard Moore, a medical liability defense attorney based in Indianapolis.

“I could foresee long COVID claims that don’t accrue until after December 2024, meaning it only becomes clear that a patient is struggling with long COVID–related symptoms after that date,” he said. “That could result in COVID claims that do not fall under the immunities.”

Mr. Moore said that if long COVID claims become truly problematic, the legislature could extend the immunities.

Other states, such as Washington, have statutes in place that increase the burden of proof for plaintiffs in cases in which care is affected by COVID and/or the treating of COVID. Elizabeth A. Leedom, a Seattle-based medical liability defense attorney, said the law would likely encompass long COVID claims if the care and treatment at issue occurred during the COVID state of emergency.

Compliance with current treatment guidelines is likely to be a good defense against any claim of delay/failure to diagnose COVID, including long COVID, she said.

Mr. Kolbert, however, doubts that the state immunities would protect against the claims.

“Courts are enforcing qualified immunities as to [traditional] COVID claims. However, I suspect that long COVID claims will fall into a category of traditional medical malpractice claim, such as delay in or failure to diagnose,” he said. In such cases, physicians “may not be able to take advantage of state-qualified immunities. Of course, this will depend upon the language of each state’s qualified immunity provisions.”

As for the statute of limitations, the clock generally starts running either when the alleged negligent conduct occurred or when the patient knew or, in the exercise of ordinary diligence, should have known, that they had been harmed by the alleged negligence, Mr. Moore said. Statutes of limitations are state specific, but the majority of states mandate a 2- to 3-year limit between the injury and the filing of a claim.

So, while the statute of limitations may be soon expiring for alleged harm that occurred during the pandemic, for patients newly diagnosed with long COVID or who have just discovered associated injuries, the clock may have just started ticking.
 

How to protect yourself against suits

Avoiding liability associated with long COVID involves the traditional legal guidance physicians are used to hearing, but with an added factor, Mr. Kolbert said.

There always needs to be communication with patients regarding the disease process, but in this area, there needs to be strong communication as to whether patients have had COVID in the past and what symptoms they are experiencing, he said. Physicians should ensure that patients know that long COVID may present in a variety of ways and that there is no definitive test for long COVID.

Physicians should document when the patient has been instructed to follow up and should take necessary steps to ensure the patient returns for follow-up care, he added.

On the opposite side of the spectrum is making sure not to assume a condition or symptom is the result of long COVID, he said. Care should be taken not to diagnose long COVID without excluding traditional causes.

“Ensure that patients know that COVID is not over, per se, and that science supports vaccination,” Mr. Kolbert said. “The best defense here is a strong communicative offense, engaging with the patient and thoughtfully charting about this.”

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

By now, concerns about COVID-related lawsuits have faded into the rear view mirror for most physicians.

But just when COVID lawsuits appear to be dwindling out, legal experts see a new lawsuit risk on the horizon – long COVID claims. While some say it’s doubtful the claims will succeed, the lawsuits could still create legal headaches for doctors in the form of time and money.

Long COVID claims are defined as complaints that allege that a diagnosis of long COVID was missed or delayed and that caused harm or injury. Lawsuits may also include claims in which patients allege that they were misdiagnosed as having long COVID when they were really suffering from another condition.

So far, a handful of long COVID claims have come down the pipeline, said Peter A. Kolbert, JD, senior vice president of claims and litigation services for Healthcare Risk Advisors, part of TDC Group.

“This is an area that is emerging as we speak,” Mr. Kolbert said. “We are starting to see these claims trickle in.”

In a recent case, for example, a patient sued her primary care physician for negligence, alleging her original SARS-CoV-2 infection was mismanaged and that this led to permanent neuropathy from long COVID. Had the patient been treated appropriately, the patient contends, she would not have developed long COVID or the resulting neuropathy, said Mr. Kolbert. An outcome in the case has not yet been reached, added Mr. Kolbert, who heard about the claim from a colleague.

The increase in the number of lawsuits raises concerns about how courts and juries might decide long COVID claims when so much about the condition is still unknown and best treatment practices are still developing. Research shows that long COVID occurs in at least 10% of cases of SARS-CoV-2 infection, and more than 200 symptoms have been identified. A Kaiser Family Foundation study found that 15% of the U.S. population believe they have experienced the symptoms of long COVID at some point, and 6% of people believe they currently have long COVID.

The risk of long COVID lawsuits underscores the importance of physicians taking proactive steps to protect themselves from liability when treating patients who might have the condition, say legal experts.

“There are legal standards that say new, unestablished scientific principles shouldn’t be first tested by a jury, they should be recognized and established within their [professional] area,” Mr. Kolbert said. “While we are seeing lawsuits related to long COVID, I think it is truly putting the cart before the horse, because there needs to be societal recognition that we’re still learning how to define and treat long COVID.”
 

What are patients alleging?

In the few long COVID claims that have arisen, some complaints have alleged delay in the recognition and treatment of long COVID, according to Mr. Kolbert. There have also been claims that physicians failed to refer a patient with long COVID to a specialist in a timely way and that this results in the patient’s experiencing chronic fatigue or a neuropathy.

Fatigue is one of the most common symptoms associated with long COVID, according to recent studies. Other symptoms include postexertional malaise, brain fog, and gastrointestinal problems.

Another rising legal theme is failure to adequately communicate with patients about what long COVID is and what it entails.

Whether plaintiffs who bring long COVID claims will be successful in court remains a question.

Andrew D. DeSimone, JD, a Lexington, Ky.–based medical malpractice defense attorney, said he has not seen any claims involving long COVID. He added that a long COVID claim would be challenging to prove, considering the standard of care for treating the condition is still evolving. Plaintiffs in a medical malpractice action must prove that physicians owed a duty of care to the patient, that the doctor breached that duty by failing to conform to the standard of care, and that the breach caused an injury that harmed the patient.

Mr. DeSimone also doubts whether juries would be very sympathetic to such plaintiffs.

“There’s a lot of fatigue around COVID still,” he said. “I don’t know if a jury would buy into someone claiming long COVID. I think the claim would have a hard time gaining traction. Not that it’s impossible.”

Another unanswered question is whether legal protections enacted by states during the pandemic might apply to long COVID claims.

Shortly after the pandemic started, most states enacted laws or executive orders that shielded physicians from liability claims relating to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proved. The U.S. Department of Health and Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19.

Some of these state immunities have since expired. Other states have extended their legal protections for short periods. In Indiana, for example, physicians and businesses are protected until Dec. 31, 2024, from civil tort actions that allege damages arising from COVID-19.

It’s possible that in long COVID lawsuits, physicians would be protected by the immunities unless the cases come after the protections expire, said J. Richard Moore, a medical liability defense attorney based in Indianapolis.

“I could foresee long COVID claims that don’t accrue until after December 2024, meaning it only becomes clear that a patient is struggling with long COVID–related symptoms after that date,” he said. “That could result in COVID claims that do not fall under the immunities.”

Mr. Moore said that if long COVID claims become truly problematic, the legislature could extend the immunities.

Other states, such as Washington, have statutes in place that increase the burden of proof for plaintiffs in cases in which care is affected by COVID and/or the treating of COVID. Elizabeth A. Leedom, a Seattle-based medical liability defense attorney, said the law would likely encompass long COVID claims if the care and treatment at issue occurred during the COVID state of emergency.

Compliance with current treatment guidelines is likely to be a good defense against any claim of delay/failure to diagnose COVID, including long COVID, she said.

Mr. Kolbert, however, doubts that the state immunities would protect against the claims.

“Courts are enforcing qualified immunities as to [traditional] COVID claims. However, I suspect that long COVID claims will fall into a category of traditional medical malpractice claim, such as delay in or failure to diagnose,” he said. In such cases, physicians “may not be able to take advantage of state-qualified immunities. Of course, this will depend upon the language of each state’s qualified immunity provisions.”

As for the statute of limitations, the clock generally starts running either when the alleged negligent conduct occurred or when the patient knew or, in the exercise of ordinary diligence, should have known, that they had been harmed by the alleged negligence, Mr. Moore said. Statutes of limitations are state specific, but the majority of states mandate a 2- to 3-year limit between the injury and the filing of a claim.

So, while the statute of limitations may be soon expiring for alleged harm that occurred during the pandemic, for patients newly diagnosed with long COVID or who have just discovered associated injuries, the clock may have just started ticking.
 

How to protect yourself against suits

Avoiding liability associated with long COVID involves the traditional legal guidance physicians are used to hearing, but with an added factor, Mr. Kolbert said.

There always needs to be communication with patients regarding the disease process, but in this area, there needs to be strong communication as to whether patients have had COVID in the past and what symptoms they are experiencing, he said. Physicians should ensure that patients know that long COVID may present in a variety of ways and that there is no definitive test for long COVID.

Physicians should document when the patient has been instructed to follow up and should take necessary steps to ensure the patient returns for follow-up care, he added.

On the opposite side of the spectrum is making sure not to assume a condition or symptom is the result of long COVID, he said. Care should be taken not to diagnose long COVID without excluding traditional causes.

“Ensure that patients know that COVID is not over, per se, and that science supports vaccination,” Mr. Kolbert said. “The best defense here is a strong communicative offense, engaging with the patient and thoughtfully charting about this.”

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

By now, concerns about COVID-related lawsuits have faded into the rear view mirror for most physicians.

But just when COVID lawsuits appear to be dwindling out, legal experts see a new lawsuit risk on the horizon – long COVID claims. While some say it’s doubtful the claims will succeed, the lawsuits could still create legal headaches for doctors in the form of time and money.

Long COVID claims are defined as complaints that allege that a diagnosis of long COVID was missed or delayed and that caused harm or injury. Lawsuits may also include claims in which patients allege that they were misdiagnosed as having long COVID when they were really suffering from another condition.

So far, a handful of long COVID claims have come down the pipeline, said Peter A. Kolbert, JD, senior vice president of claims and litigation services for Healthcare Risk Advisors, part of TDC Group.

“This is an area that is emerging as we speak,” Mr. Kolbert said. “We are starting to see these claims trickle in.”

In a recent case, for example, a patient sued her primary care physician for negligence, alleging her original SARS-CoV-2 infection was mismanaged and that this led to permanent neuropathy from long COVID. Had the patient been treated appropriately, the patient contends, she would not have developed long COVID or the resulting neuropathy, said Mr. Kolbert. An outcome in the case has not yet been reached, added Mr. Kolbert, who heard about the claim from a colleague.

The increase in the number of lawsuits raises concerns about how courts and juries might decide long COVID claims when so much about the condition is still unknown and best treatment practices are still developing. Research shows that long COVID occurs in at least 10% of cases of SARS-CoV-2 infection, and more than 200 symptoms have been identified. A Kaiser Family Foundation study found that 15% of the U.S. population believe they have experienced the symptoms of long COVID at some point, and 6% of people believe they currently have long COVID.

The risk of long COVID lawsuits underscores the importance of physicians taking proactive steps to protect themselves from liability when treating patients who might have the condition, say legal experts.

“There are legal standards that say new, unestablished scientific principles shouldn’t be first tested by a jury, they should be recognized and established within their [professional] area,” Mr. Kolbert said. “While we are seeing lawsuits related to long COVID, I think it is truly putting the cart before the horse, because there needs to be societal recognition that we’re still learning how to define and treat long COVID.”
 

What are patients alleging?

In the few long COVID claims that have arisen, some complaints have alleged delay in the recognition and treatment of long COVID, according to Mr. Kolbert. There have also been claims that physicians failed to refer a patient with long COVID to a specialist in a timely way and that this results in the patient’s experiencing chronic fatigue or a neuropathy.

Fatigue is one of the most common symptoms associated with long COVID, according to recent studies. Other symptoms include postexertional malaise, brain fog, and gastrointestinal problems.

Another rising legal theme is failure to adequately communicate with patients about what long COVID is and what it entails.

Whether plaintiffs who bring long COVID claims will be successful in court remains a question.

Andrew D. DeSimone, JD, a Lexington, Ky.–based medical malpractice defense attorney, said he has not seen any claims involving long COVID. He added that a long COVID claim would be challenging to prove, considering the standard of care for treating the condition is still evolving. Plaintiffs in a medical malpractice action must prove that physicians owed a duty of care to the patient, that the doctor breached that duty by failing to conform to the standard of care, and that the breach caused an injury that harmed the patient.

Mr. DeSimone also doubts whether juries would be very sympathetic to such plaintiffs.

“There’s a lot of fatigue around COVID still,” he said. “I don’t know if a jury would buy into someone claiming long COVID. I think the claim would have a hard time gaining traction. Not that it’s impossible.”

Another unanswered question is whether legal protections enacted by states during the pandemic might apply to long COVID claims.

Shortly after the pandemic started, most states enacted laws or executive orders that shielded physicians from liability claims relating to the prevention and treatment of COVID-19, unless gross negligence or willful misconduct is proved. The U.S. Department of Health and Human Services published a declaration under the Public Readiness and Emergency Preparedness Act (PREP Act) that provided liability immunity to health care professionals for any activity related to medical countermeasures against COVID-19.

Some of these state immunities have since expired. Other states have extended their legal protections for short periods. In Indiana, for example, physicians and businesses are protected until Dec. 31, 2024, from civil tort actions that allege damages arising from COVID-19.

It’s possible that in long COVID lawsuits, physicians would be protected by the immunities unless the cases come after the protections expire, said J. Richard Moore, a medical liability defense attorney based in Indianapolis.

“I could foresee long COVID claims that don’t accrue until after December 2024, meaning it only becomes clear that a patient is struggling with long COVID–related symptoms after that date,” he said. “That could result in COVID claims that do not fall under the immunities.”

Mr. Moore said that if long COVID claims become truly problematic, the legislature could extend the immunities.

Other states, such as Washington, have statutes in place that increase the burden of proof for plaintiffs in cases in which care is affected by COVID and/or the treating of COVID. Elizabeth A. Leedom, a Seattle-based medical liability defense attorney, said the law would likely encompass long COVID claims if the care and treatment at issue occurred during the COVID state of emergency.

Compliance with current treatment guidelines is likely to be a good defense against any claim of delay/failure to diagnose COVID, including long COVID, she said.

Mr. Kolbert, however, doubts that the state immunities would protect against the claims.

“Courts are enforcing qualified immunities as to [traditional] COVID claims. However, I suspect that long COVID claims will fall into a category of traditional medical malpractice claim, such as delay in or failure to diagnose,” he said. In such cases, physicians “may not be able to take advantage of state-qualified immunities. Of course, this will depend upon the language of each state’s qualified immunity provisions.”

As for the statute of limitations, the clock generally starts running either when the alleged negligent conduct occurred or when the patient knew or, in the exercise of ordinary diligence, should have known, that they had been harmed by the alleged negligence, Mr. Moore said. Statutes of limitations are state specific, but the majority of states mandate a 2- to 3-year limit between the injury and the filing of a claim.

So, while the statute of limitations may be soon expiring for alleged harm that occurred during the pandemic, for patients newly diagnosed with long COVID or who have just discovered associated injuries, the clock may have just started ticking.
 

How to protect yourself against suits

Avoiding liability associated with long COVID involves the traditional legal guidance physicians are used to hearing, but with an added factor, Mr. Kolbert said.

There always needs to be communication with patients regarding the disease process, but in this area, there needs to be strong communication as to whether patients have had COVID in the past and what symptoms they are experiencing, he said. Physicians should ensure that patients know that long COVID may present in a variety of ways and that there is no definitive test for long COVID.

Physicians should document when the patient has been instructed to follow up and should take necessary steps to ensure the patient returns for follow-up care, he added.

On the opposite side of the spectrum is making sure not to assume a condition or symptom is the result of long COVID, he said. Care should be taken not to diagnose long COVID without excluding traditional causes.

“Ensure that patients know that COVID is not over, per se, and that science supports vaccination,” Mr. Kolbert said. “The best defense here is a strong communicative offense, engaging with the patient and thoughtfully charting about this.”

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

Long COVID most often strikes seniors and adults, but children are also affected, even though they get less attention, new research shows.

Experts noted that the disease poses particular challenges for children and the doctors who treat them.

Parents and doctors need to be on the lookout for symptoms of long COVID in children and teens that might be easily missed or misdiagnosed, according to physicians and family groups.

Children are at lower risk for contracting COVID and often experience milder symptoms. But the virus is now widespread, and a recent study found that around 16% of pediatric patients with COVID go on to develop symptoms that last more than 3 months – the working definition of long COVID.

Parents and doctors are calling for more studies and more awareness.

Diane Sheehan, who lives outside Charlotte, N.C., says she was an active person and is now permanently disabled from long COVID. Her teenage son has it too and is still recovering.

He contracted COVID after a school event, she said. He had a mild case, but then he started experiencing dizziness and would even experience loss of consciousness when he stood up suddenly. After he contracted the virus a second time, he was bedridden for 8 months.

The staff at Hackensack Meridian Health, a pediatric long COVID clinic in New Jersey, has been working with area schools to help teachers and school nurses recognize possible long COVID in children and young people. The clinic is one of about a dozen in the United States that specializes in pediatric cases.

Katherine Clouser, MD, a pediatric hospital medicine specialist, has been with the clinic since it opened in 2021, and she’s seen a steady flow of patients. Some get better, but she sees a few new cases each week.

“We are seeing children who are having a difficult time returning to school and sports,” she said.

The clinic is having success with a mix of approaches, including intensive rehabilitation, talk therapy, and some off-label use of nirmatrelvir (Paxlovid), an antiviral now being studied as a treatment for long COVID through a National Institutes of Health clinical trials initiative that was announced last month.

Treatment depends on symptoms and is determined on a case-by-case basis, Dr. Clouser said.

Families of her patients are grateful, she added.

“We hear a lot of parents who were desperate for someone to believe them – or someone who knows about it,” she said.

A recent review of more than 30 studies with about 15,000 participants concluded that 16.2% (95% confidence interval, 8.5%-28.6%) of the pediatric participants experienced one or more persistent symptoms of long COVID at least 3 months after acute infection.

Estimates of the number of children and youth with long COVID have varied widely. A 2022 study put the number at more than 25% of cases, but the American Academy of Pediatrics notes that estimates of the percentage of children infected with SARS-CoV-2 who go on to have long COVID range from 2% to 66%.

The federal Recover Initiative has enrolled more than 10,000 children and youth – a number it plans to double – and studies of electronic health records are underway. The Recover pediatric team is also setting up a cohort that they plan to follow into 2025.

Some clinics are having luck treating young people with approaches ranging from special diets to off-label medication.

David W. Miller, MD, who runs the long COVID clinic at the UH Rainbow Babies and Children’s Hospital, Cleveland, said he’s seen about 250 patients.

A warning sign of long COVID in children is profound fatigue, he said.

“It’s the most common symptom,” Dr. Miller said. “They feel like they have the flu all the time.”

Many also experience orthostatic hypotension on standing, triggering dizziness.

He said his team targets symptom groups. Initial management consists of a diet without sugar or refined carbohydrates. Skipping pasta and sweets can be hard for young people, but Dr. Miller said sometimes the diet alone helps.

Many have vitamin D and iron deficiencies. Others need help getting a good night’s sleep. He’s treated 50 with off-label low-dose naltrexone.

Some people with long COVID – both young and old – complain about being misdiagnosed as having depression. Dr. Miller says he see a lot of anxiety – some situational and some biochemical – in pediatric patients. But he cautions doctors not to treat their illness solely as a mental health problem.

His advice: If a young person or child experiences a major change in his or her regular level of functioning or has multiple COVID symptoms that don’t go away after several months, parents and doctors should consider long COVID as a possible cause.

Dr. Miller said most of his patients get better over time with some treatments: “We see improvement in the majority of kids who can stick to the regimen,” such as a sugar-free diet, supplements, and adequate sleep. Recovery has been slow and incomplete for Diane Sheehan and her son. She was training as a permanent make-up artist, she said, but now has hand tremors that make work impossible.

She has found doctors who treat some of her symptoms with antihistamines, and her son has benefited from physical therapy.

But for now, her son is passing on a scholarship he was awarded to attend North Carolina State University this year. Instead, he’s living at home and going to a local college.

Ms. Sheehan urges parents to be on the alert for signs that their children might have long COVID, which can be confused with many other conditions.

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

Long COVID most often strikes seniors and adults, but children are also affected, even though they get less attention, new research shows.

Experts noted that the disease poses particular challenges for children and the doctors who treat them.

Parents and doctors need to be on the lookout for symptoms of long COVID in children and teens that might be easily missed or misdiagnosed, according to physicians and family groups.

Children are at lower risk for contracting COVID and often experience milder symptoms. But the virus is now widespread, and a recent study found that around 16% of pediatric patients with COVID go on to develop symptoms that last more than 3 months – the working definition of long COVID.

Parents and doctors are calling for more studies and more awareness.

Diane Sheehan, who lives outside Charlotte, N.C., says she was an active person and is now permanently disabled from long COVID. Her teenage son has it too and is still recovering.

He contracted COVID after a school event, she said. He had a mild case, but then he started experiencing dizziness and would even experience loss of consciousness when he stood up suddenly. After he contracted the virus a second time, he was bedridden for 8 months.

The staff at Hackensack Meridian Health, a pediatric long COVID clinic in New Jersey, has been working with area schools to help teachers and school nurses recognize possible long COVID in children and young people. The clinic is one of about a dozen in the United States that specializes in pediatric cases.

Katherine Clouser, MD, a pediatric hospital medicine specialist, has been with the clinic since it opened in 2021, and she’s seen a steady flow of patients. Some get better, but she sees a few new cases each week.

“We are seeing children who are having a difficult time returning to school and sports,” she said.

The clinic is having success with a mix of approaches, including intensive rehabilitation, talk therapy, and some off-label use of nirmatrelvir (Paxlovid), an antiviral now being studied as a treatment for long COVID through a National Institutes of Health clinical trials initiative that was announced last month.

Treatment depends on symptoms and is determined on a case-by-case basis, Dr. Clouser said.

Families of her patients are grateful, she added.

“We hear a lot of parents who were desperate for someone to believe them – or someone who knows about it,” she said.

A recent review of more than 30 studies with about 15,000 participants concluded that 16.2% (95% confidence interval, 8.5%-28.6%) of the pediatric participants experienced one or more persistent symptoms of long COVID at least 3 months after acute infection.

Estimates of the number of children and youth with long COVID have varied widely. A 2022 study put the number at more than 25% of cases, but the American Academy of Pediatrics notes that estimates of the percentage of children infected with SARS-CoV-2 who go on to have long COVID range from 2% to 66%.

The federal Recover Initiative has enrolled more than 10,000 children and youth – a number it plans to double – and studies of electronic health records are underway. The Recover pediatric team is also setting up a cohort that they plan to follow into 2025.

Some clinics are having luck treating young people with approaches ranging from special diets to off-label medication.

David W. Miller, MD, who runs the long COVID clinic at the UH Rainbow Babies and Children’s Hospital, Cleveland, said he’s seen about 250 patients.

A warning sign of long COVID in children is profound fatigue, he said.

“It’s the most common symptom,” Dr. Miller said. “They feel like they have the flu all the time.”

Many also experience orthostatic hypotension on standing, triggering dizziness.

He said his team targets symptom groups. Initial management consists of a diet without sugar or refined carbohydrates. Skipping pasta and sweets can be hard for young people, but Dr. Miller said sometimes the diet alone helps.

Many have vitamin D and iron deficiencies. Others need help getting a good night’s sleep. He’s treated 50 with off-label low-dose naltrexone.

Some people with long COVID – both young and old – complain about being misdiagnosed as having depression. Dr. Miller says he see a lot of anxiety – some situational and some biochemical – in pediatric patients. But he cautions doctors not to treat their illness solely as a mental health problem.

His advice: If a young person or child experiences a major change in his or her regular level of functioning or has multiple COVID symptoms that don’t go away after several months, parents and doctors should consider long COVID as a possible cause.

Dr. Miller said most of his patients get better over time with some treatments: “We see improvement in the majority of kids who can stick to the regimen,” such as a sugar-free diet, supplements, and adequate sleep. Recovery has been slow and incomplete for Diane Sheehan and her son. She was training as a permanent make-up artist, she said, but now has hand tremors that make work impossible.

She has found doctors who treat some of her symptoms with antihistamines, and her son has benefited from physical therapy.

But for now, her son is passing on a scholarship he was awarded to attend North Carolina State University this year. Instead, he’s living at home and going to a local college.

Ms. Sheehan urges parents to be on the alert for signs that their children might have long COVID, which can be confused with many other conditions.

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

Long COVID most often strikes seniors and adults, but children are also affected, even though they get less attention, new research shows.

Experts noted that the disease poses particular challenges for children and the doctors who treat them.

Parents and doctors need to be on the lookout for symptoms of long COVID in children and teens that might be easily missed or misdiagnosed, according to physicians and family groups.

Children are at lower risk for contracting COVID and often experience milder symptoms. But the virus is now widespread, and a recent study found that around 16% of pediatric patients with COVID go on to develop symptoms that last more than 3 months – the working definition of long COVID.

Parents and doctors are calling for more studies and more awareness.

Diane Sheehan, who lives outside Charlotte, N.C., says she was an active person and is now permanently disabled from long COVID. Her teenage son has it too and is still recovering.

He contracted COVID after a school event, she said. He had a mild case, but then he started experiencing dizziness and would even experience loss of consciousness when he stood up suddenly. After he contracted the virus a second time, he was bedridden for 8 months.

The staff at Hackensack Meridian Health, a pediatric long COVID clinic in New Jersey, has been working with area schools to help teachers and school nurses recognize possible long COVID in children and young people. The clinic is one of about a dozen in the United States that specializes in pediatric cases.

Katherine Clouser, MD, a pediatric hospital medicine specialist, has been with the clinic since it opened in 2021, and she’s seen a steady flow of patients. Some get better, but she sees a few new cases each week.

“We are seeing children who are having a difficult time returning to school and sports,” she said.

The clinic is having success with a mix of approaches, including intensive rehabilitation, talk therapy, and some off-label use of nirmatrelvir (Paxlovid), an antiviral now being studied as a treatment for long COVID through a National Institutes of Health clinical trials initiative that was announced last month.

Treatment depends on symptoms and is determined on a case-by-case basis, Dr. Clouser said.

Families of her patients are grateful, she added.

“We hear a lot of parents who were desperate for someone to believe them – or someone who knows about it,” she said.

A recent review of more than 30 studies with about 15,000 participants concluded that 16.2% (95% confidence interval, 8.5%-28.6%) of the pediatric participants experienced one or more persistent symptoms of long COVID at least 3 months after acute infection.

Estimates of the number of children and youth with long COVID have varied widely. A 2022 study put the number at more than 25% of cases, but the American Academy of Pediatrics notes that estimates of the percentage of children infected with SARS-CoV-2 who go on to have long COVID range from 2% to 66%.

The federal Recover Initiative has enrolled more than 10,000 children and youth – a number it plans to double – and studies of electronic health records are underway. The Recover pediatric team is also setting up a cohort that they plan to follow into 2025.

Some clinics are having luck treating young people with approaches ranging from special diets to off-label medication.

David W. Miller, MD, who runs the long COVID clinic at the UH Rainbow Babies and Children’s Hospital, Cleveland, said he’s seen about 250 patients.

A warning sign of long COVID in children is profound fatigue, he said.

“It’s the most common symptom,” Dr. Miller said. “They feel like they have the flu all the time.”

Many also experience orthostatic hypotension on standing, triggering dizziness.

He said his team targets symptom groups. Initial management consists of a diet without sugar or refined carbohydrates. Skipping pasta and sweets can be hard for young people, but Dr. Miller said sometimes the diet alone helps.

Many have vitamin D and iron deficiencies. Others need help getting a good night’s sleep. He’s treated 50 with off-label low-dose naltrexone.

Some people with long COVID – both young and old – complain about being misdiagnosed as having depression. Dr. Miller says he see a lot of anxiety – some situational and some biochemical – in pediatric patients. But he cautions doctors not to treat their illness solely as a mental health problem.

His advice: If a young person or child experiences a major change in his or her regular level of functioning or has multiple COVID symptoms that don’t go away after several months, parents and doctors should consider long COVID as a possible cause.

Dr. Miller said most of his patients get better over time with some treatments: “We see improvement in the majority of kids who can stick to the regimen,” such as a sugar-free diet, supplements, and adequate sleep. Recovery has been slow and incomplete for Diane Sheehan and her son. She was training as a permanent make-up artist, she said, but now has hand tremors that make work impossible.

She has found doctors who treat some of her symptoms with antihistamines, and her son has benefited from physical therapy.

But for now, her son is passing on a scholarship he was awarded to attend North Carolina State University this year. Instead, he’s living at home and going to a local college.

Ms. Sheehan urges parents to be on the alert for signs that their children might have long COVID, which can be confused with many other conditions.

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

Approximately one-quarter of adults who experience long COVID report activity limitations that do not change over time, based on data from national sample of nonhospitalized individuals.

Symptoms of long COVID, an ongoing medical condition that occurs in the wake of COVID-19 infection, include respiratory, neurologic, cardiovascular, or other complications that may last for weeks, months, or years after infection.

Current estimates of the incidence of long COVID in the United States range from 7.5% to 41%, according to Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Long COVID has shown a significant effect on patients’ quality of life, functional status, and ability to work, but the impact on activity limitation in particular has not been examined, the researchers said.

In a study published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR), the researchers reviewed data from surveys conducted between June 1 and 13, 2022, and June 7 and 19, 2023. The data came from the Census Bureau’s Household Pulse Survey (HPS), a cross-sectional national survey designed to measure the social and economic effects of COVID-19 on U.S. households. Surveys were conducted in 2-week cycles (2 weeks on, 2 weeks off). Questions about long COVID were added to the survey beginning on June 1, 2022, and questions about activity limitations from long COVID were added on Sept. 14, 2022, including questions about participants’ abilities to perform daily activities before and after COVID-19 infection.

Overall, the prevalence of long COVID decreased from 7.5% to 6.0% in U.S. adults aged 18 years and older during the study period. However, when stratified by age group, the decline was significant only in adults older than 60 years, and 1 in 10 adults with a history of COVID-19 reported long COVID at the end of the study period.

Among respondents with long COVID, 26.4% of respondents for time period of June 7-19, 2023, reported significant activity limitations, which remained unchanged over time, with no clear pattern in activity limitations across age groups, the researchers said.

Prevalence of long COVID was highest for individuals in middle adulthood (aged 30-39 years, 40-49 years, and 50-59 years) and lowest for younger adults (18-29 years) and older adults (aged 60 years and older). The prevalence of long COVID decreased by 1.16% per survey cycle between the June 1-13 and Jan. 4-16 cycles, but then remained stable, with a decrease of 0.01% per cycle between June 1-13, 2022, and Jan. 4-16, 2023.

Previous studies have shown that activity limitations resulting from long COVID can significantly affect quality of life and functional status, as well as the ability to work or care for others. A recent study in the United Kingdom showed that quality of life scores among long COVID patients were similar to those of individuals with advanced cancer, and more than half of the long COVID patients reported moderately severe functional impairment. “The larger economic and societal impact of long COVID could be far-reaching if working-age adults are unable to maintain employment or care for children or aging parents,” the researchers said.

The current study findings were limited by several factors including potential coverage bias in the survey sample, the relatively low survey response rate, and the inability to collect data on duration of symptoms, COVID-19 vaccination status, treatment during acute infection, and time since COVID-19 illness; any of these factors could affect the reported prevalence of long COVID, the researchers noted.

However, the results suggest the need for continued attention to COVID-19 prevention efforts, including not only staying current with recommended COVID-19 vaccination, but also planning for symptom management and health care service needs of long COVID patients, they concluded.
 

More data are needed to tease out patterns

“Physicians and patients are still trying to understand long COVID and its implications for the health of affected individuals,” said Noel Deep, MD, in an interview.

The current study shows a prevalence of long COVID in approximately 11% of COVID patients, which is a significant number, said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study also was useful to illustrate a decline in the incidence of people affected by long COVID symptoms in the United States and in other countries, he said.

Dr. Deep noted that despite the persistent prevalence of long COVID symptoms overall, he was encouraged by the findings that older adults “who tend to have other underlying health conditions that could put them at a higher risk for adverse health outcomes” reported fewer long COVID symptoms than younger adults.

However, he noted that the high incidence of long COVID symptoms in able-bodied individuals in their 30s and 40s may affect their the economic situations as well as their ability to care for elderly relatives and children who might be dependent on them.

“Physicians and other clinicians should be aware of the symptoms and impacts caused by long COVID,” Dr. Deep said in an interview. “These individuals usually present with a myriad of vague and varying symptoms. Physicians should be cognizant of this situation, ask about previous infection with COVID-19, and utilize the resources of long COVID clinics where available,” he said.

Several factors can affect the assessment and management of patients with long COVID symptoms in primary care practices, said Dr. Deep. First and foremost are the time constraints of detailed evaluation and testing, he said.

Second, primary care clinicians need to be aware of the different symptoms that may be indicative of long COVID including fatigue, neurocognitive symptoms such as brain fog or memory disturbance, respiratory symptoms, and cardiovascular symptoms, as well as olfactory and gustatory symptoms. “These symptoms can be confounded by underlying health conditions, especially in elderly individuals,” he noted.

“Recommendations and guidelines are evolving regarding the evaluation and management of patients with long COVID that should help physicians and other clinicians in the future,” said Dr. Deep.

In the meantime, having a high index of suspicion, paying attention to the symptoms described by the patient, and taking a proper history with regard to previous COVID-19 infection should help overcome some of these challenges, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

Approximately one-quarter of adults who experience long COVID report activity limitations that do not change over time, based on data from national sample of nonhospitalized individuals.

Symptoms of long COVID, an ongoing medical condition that occurs in the wake of COVID-19 infection, include respiratory, neurologic, cardiovascular, or other complications that may last for weeks, months, or years after infection.

Current estimates of the incidence of long COVID in the United States range from 7.5% to 41%, according to Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Long COVID has shown a significant effect on patients’ quality of life, functional status, and ability to work, but the impact on activity limitation in particular has not been examined, the researchers said.

In a study published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR), the researchers reviewed data from surveys conducted between June 1 and 13, 2022, and June 7 and 19, 2023. The data came from the Census Bureau’s Household Pulse Survey (HPS), a cross-sectional national survey designed to measure the social and economic effects of COVID-19 on U.S. households. Surveys were conducted in 2-week cycles (2 weeks on, 2 weeks off). Questions about long COVID were added to the survey beginning on June 1, 2022, and questions about activity limitations from long COVID were added on Sept. 14, 2022, including questions about participants’ abilities to perform daily activities before and after COVID-19 infection.

Overall, the prevalence of long COVID decreased from 7.5% to 6.0% in U.S. adults aged 18 years and older during the study period. However, when stratified by age group, the decline was significant only in adults older than 60 years, and 1 in 10 adults with a history of COVID-19 reported long COVID at the end of the study period.

Among respondents with long COVID, 26.4% of respondents for time period of June 7-19, 2023, reported significant activity limitations, which remained unchanged over time, with no clear pattern in activity limitations across age groups, the researchers said.

Prevalence of long COVID was highest for individuals in middle adulthood (aged 30-39 years, 40-49 years, and 50-59 years) and lowest for younger adults (18-29 years) and older adults (aged 60 years and older). The prevalence of long COVID decreased by 1.16% per survey cycle between the June 1-13 and Jan. 4-16 cycles, but then remained stable, with a decrease of 0.01% per cycle between June 1-13, 2022, and Jan. 4-16, 2023.

Previous studies have shown that activity limitations resulting from long COVID can significantly affect quality of life and functional status, as well as the ability to work or care for others. A recent study in the United Kingdom showed that quality of life scores among long COVID patients were similar to those of individuals with advanced cancer, and more than half of the long COVID patients reported moderately severe functional impairment. “The larger economic and societal impact of long COVID could be far-reaching if working-age adults are unable to maintain employment or care for children or aging parents,” the researchers said.

The current study findings were limited by several factors including potential coverage bias in the survey sample, the relatively low survey response rate, and the inability to collect data on duration of symptoms, COVID-19 vaccination status, treatment during acute infection, and time since COVID-19 illness; any of these factors could affect the reported prevalence of long COVID, the researchers noted.

However, the results suggest the need for continued attention to COVID-19 prevention efforts, including not only staying current with recommended COVID-19 vaccination, but also planning for symptom management and health care service needs of long COVID patients, they concluded.
 

More data are needed to tease out patterns

“Physicians and patients are still trying to understand long COVID and its implications for the health of affected individuals,” said Noel Deep, MD, in an interview.

The current study shows a prevalence of long COVID in approximately 11% of COVID patients, which is a significant number, said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study also was useful to illustrate a decline in the incidence of people affected by long COVID symptoms in the United States and in other countries, he said.

Dr. Deep noted that despite the persistent prevalence of long COVID symptoms overall, he was encouraged by the findings that older adults “who tend to have other underlying health conditions that could put them at a higher risk for adverse health outcomes” reported fewer long COVID symptoms than younger adults.

However, he noted that the high incidence of long COVID symptoms in able-bodied individuals in their 30s and 40s may affect their the economic situations as well as their ability to care for elderly relatives and children who might be dependent on them.

“Physicians and other clinicians should be aware of the symptoms and impacts caused by long COVID,” Dr. Deep said in an interview. “These individuals usually present with a myriad of vague and varying symptoms. Physicians should be cognizant of this situation, ask about previous infection with COVID-19, and utilize the resources of long COVID clinics where available,” he said.

Several factors can affect the assessment and management of patients with long COVID symptoms in primary care practices, said Dr. Deep. First and foremost are the time constraints of detailed evaluation and testing, he said.

Second, primary care clinicians need to be aware of the different symptoms that may be indicative of long COVID including fatigue, neurocognitive symptoms such as brain fog or memory disturbance, respiratory symptoms, and cardiovascular symptoms, as well as olfactory and gustatory symptoms. “These symptoms can be confounded by underlying health conditions, especially in elderly individuals,” he noted.

“Recommendations and guidelines are evolving regarding the evaluation and management of patients with long COVID that should help physicians and other clinicians in the future,” said Dr. Deep.

In the meantime, having a high index of suspicion, paying attention to the symptoms described by the patient, and taking a proper history with regard to previous COVID-19 infection should help overcome some of these challenges, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

Approximately one-quarter of adults who experience long COVID report activity limitations that do not change over time, based on data from national sample of nonhospitalized individuals.

Symptoms of long COVID, an ongoing medical condition that occurs in the wake of COVID-19 infection, include respiratory, neurologic, cardiovascular, or other complications that may last for weeks, months, or years after infection.

Current estimates of the incidence of long COVID in the United States range from 7.5% to 41%, according to Nicole D. Ford, PhD, of the Centers for Disease Control and Prevention, Atlanta, and colleagues. Long COVID has shown a significant effect on patients’ quality of life, functional status, and ability to work, but the impact on activity limitation in particular has not been examined, the researchers said.

In a study published in the Centers for Disease Control and Prevention’s Morbidity and Mortality Weekly Report (MMWR), the researchers reviewed data from surveys conducted between June 1 and 13, 2022, and June 7 and 19, 2023. The data came from the Census Bureau’s Household Pulse Survey (HPS), a cross-sectional national survey designed to measure the social and economic effects of COVID-19 on U.S. households. Surveys were conducted in 2-week cycles (2 weeks on, 2 weeks off). Questions about long COVID were added to the survey beginning on June 1, 2022, and questions about activity limitations from long COVID were added on Sept. 14, 2022, including questions about participants’ abilities to perform daily activities before and after COVID-19 infection.

Overall, the prevalence of long COVID decreased from 7.5% to 6.0% in U.S. adults aged 18 years and older during the study period. However, when stratified by age group, the decline was significant only in adults older than 60 years, and 1 in 10 adults with a history of COVID-19 reported long COVID at the end of the study period.

Among respondents with long COVID, 26.4% of respondents for time period of June 7-19, 2023, reported significant activity limitations, which remained unchanged over time, with no clear pattern in activity limitations across age groups, the researchers said.

Prevalence of long COVID was highest for individuals in middle adulthood (aged 30-39 years, 40-49 years, and 50-59 years) and lowest for younger adults (18-29 years) and older adults (aged 60 years and older). The prevalence of long COVID decreased by 1.16% per survey cycle between the June 1-13 and Jan. 4-16 cycles, but then remained stable, with a decrease of 0.01% per cycle between June 1-13, 2022, and Jan. 4-16, 2023.

Previous studies have shown that activity limitations resulting from long COVID can significantly affect quality of life and functional status, as well as the ability to work or care for others. A recent study in the United Kingdom showed that quality of life scores among long COVID patients were similar to those of individuals with advanced cancer, and more than half of the long COVID patients reported moderately severe functional impairment. “The larger economic and societal impact of long COVID could be far-reaching if working-age adults are unable to maintain employment or care for children or aging parents,” the researchers said.

The current study findings were limited by several factors including potential coverage bias in the survey sample, the relatively low survey response rate, and the inability to collect data on duration of symptoms, COVID-19 vaccination status, treatment during acute infection, and time since COVID-19 illness; any of these factors could affect the reported prevalence of long COVID, the researchers noted.

However, the results suggest the need for continued attention to COVID-19 prevention efforts, including not only staying current with recommended COVID-19 vaccination, but also planning for symptom management and health care service needs of long COVID patients, they concluded.
 

More data are needed to tease out patterns

“Physicians and patients are still trying to understand long COVID and its implications for the health of affected individuals,” said Noel Deep, MD, in an interview.

The current study shows a prevalence of long COVID in approximately 11% of COVID patients, which is a significant number, said Dr. Deep, a general internist in private practice in Antigo, Wisc., who was not involved in the study. Dr. Deep also serves as chief medical officer and a staff physician at Aspirus Langlade Hospital in Antigo.

The study also was useful to illustrate a decline in the incidence of people affected by long COVID symptoms in the United States and in other countries, he said.

Dr. Deep noted that despite the persistent prevalence of long COVID symptoms overall, he was encouraged by the findings that older adults “who tend to have other underlying health conditions that could put them at a higher risk for adverse health outcomes” reported fewer long COVID symptoms than younger adults.

However, he noted that the high incidence of long COVID symptoms in able-bodied individuals in their 30s and 40s may affect their the economic situations as well as their ability to care for elderly relatives and children who might be dependent on them.

“Physicians and other clinicians should be aware of the symptoms and impacts caused by long COVID,” Dr. Deep said in an interview. “These individuals usually present with a myriad of vague and varying symptoms. Physicians should be cognizant of this situation, ask about previous infection with COVID-19, and utilize the resources of long COVID clinics where available,” he said.

Several factors can affect the assessment and management of patients with long COVID symptoms in primary care practices, said Dr. Deep. First and foremost are the time constraints of detailed evaluation and testing, he said.

Second, primary care clinicians need to be aware of the different symptoms that may be indicative of long COVID including fatigue, neurocognitive symptoms such as brain fog or memory disturbance, respiratory symptoms, and cardiovascular symptoms, as well as olfactory and gustatory symptoms. “These symptoms can be confounded by underlying health conditions, especially in elderly individuals,” he noted.

“Recommendations and guidelines are evolving regarding the evaluation and management of patients with long COVID that should help physicians and other clinicians in the future,” said Dr. Deep.

In the meantime, having a high index of suspicion, paying attention to the symptoms described by the patient, and taking a proper history with regard to previous COVID-19 infection should help overcome some of these challenges, he said.

The study received no outside funding. The researchers had no financial conflicts to disclose. Dr. Deep had no financial conflicts to disclose and serves on the Editorial Advisory Board of Internal Medicine News.

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

After catching COVID-19 for the second time in July 2022, Daniel Lewis suffered persistent headaches, chest pain, and a dangerously high heart rate. He recalls that he was also so exhausted packing for a family wedding that he had to take a break to rest each time he put something into his suitcase.

Instead of attending the wedding, the 30-year-old Washington data analyst visited his doctor, who diagnosed “some postviral thing” and prescribed rest. Mr. Lewis found a new doctor, went to a long COVID clinic, and saw multiple specialists, but a year later, he’s still sick – and disabled. He meets the federal criteria for long COVID (symptoms that last more than 4 weeks).

He now uses an electric wheelchair whenever he leaves his apartment, a far cry from his pre-COVID life, when he was training for a half marathon.

“Some doctors have genuinely tried to help,” he said. “Most don’t really know what long COVID is, and ... since there’s no official guidance on what to do with long COVID patients, they just throw up their hands and say there’s nothing to do.”

That could be changing – at least the part about official guidance. New findings published in JAMA indicate we’re getting closer to unraveling what long COVID is all about and may help refine how it is defined and diagnosed. The study identified the 37 most common symptoms of long COVID, an important step toward better understanding and treatment of the condition, which affects an estimated 65 million people worldwide.

Although the study provides a way to systematically identify the condition, the authors were clear that this is significant but that it is only a first step. Naming symptoms is very different from understanding what causes them, and understanding them is critical for developing effective treatments, said pulmonologist Bruce Levy, MD, a study coauthor who is interim chair of medicine at Brigham and Women’s Hospital and a professor of medicine at Harvard Medical School, both in Boston.

Researchers relied on self-reported symptoms from the 9,764 participants, all adults who are part of the ongoing Researching COVID to Enhance Recovery (RECOVER) Initiative, a longitudinal study run by the National Institutes of Health. Some patients had long COVID when they signed up for the study, some developed it afterward, and some had never had it, or if they had, they were unaware.

Other studies, most of them involving smaller groups of patients, have examined long COVID biomarkers, risk factors, and specific symptoms. Dr. Levy said it’s important to have a symptom-based definition of long COVID that draws from a large cohort of patients who reported on their experiences with symptoms during the aftermath of infection. However, he pointed out that because participants volunteered for the study and were not chosen on the basis of specific criteria, they may not be representative of the more general population of patients with long COVID.

“We need this kind of evidence – it’s important to have self-reported symptoms, because clearly, the patients know what they’re feeling,” Dr. Levy said. “But it’s only part of the picture.”

Dr. Levy said the definition of long COVID needs to be further refined by ongoing research, including objective assessments of clinical findings, laboratory testing, imaging, and biomarkers.

One of the notable findings in the JAMA study is that certain symptoms tend to occur in clusters. The biostatisticians and analysts who processed the data identified four subgroups of very common symptoms that appeared together in more than 80% of the long COVID patients: loss of or change in smell and taste; postexertional malaise and fatigue; brain fog, postexertional malaise, and fatigue; and fatigue, postexertional malaise, dizziness, brain fog, gastrointestinal issues, and palpitations.

Many of those symptoms are also associated with underlying conditions not related to long COVID, which makes an accurate diagnosis a challenge.

“Just the fact that they would cluster into four groups suggests that underlying all this is not just one unifying pathobiology,” Dr. Levy said. He stressed that clinicians need to understand what’s causing the symptoms before they can properly treat patients.

He pointed out that two of the possible disease-driving mechanisms are persistence of the virus and prolonged inflammation that is slow to resolve. For patients experiencing inflammation after the virus is gone, an anti-inflammatory therapy would be most appropriate.

But if they have persistent virus, “you would want to treat with an antiviral antibiotic and not quiet down the body’s antiviral inflammatory response,” he said. “How you treat the two potential underlying causes of long COVID could thus be almost diametrically opposed, so that’s part of the importance of figuring out what is the underlying cause of those symptoms, not just identifying the symptoms themselves.”

More studies are needed to determine whether long COVID is a syndrome or is related to a singular pathobiology, experts said.

That’s consistent with the impression of long COVID researcher Harlan Krumholz, MD, the Harold H. Hines Jr. professor of medicine (cardiology) at Yale University, New Haven, Conn.

Dr. Krumholz worries that some clinicians might use the JAMA findings to dismiss patients whose symptoms meet the criteria in the scoring system developed for the study.

“It’s important for people who read this paper to know that this is preliminary,” said Dr. Krumholz, a principal investigator of another patient-focused study designed to understand long COVID – the Yale Listen to Immune, Symptom, and Treatment Experiences Now (LISTEN) Study. “It’s a condition we don’t understand yet.”

Dr. Krumholz said he has lost track of the number of patients he knows who, like Daniel Lewis, are ill and are unable to get answers. “There is an intense sense of inadequacy on the clinical side and the research side,” he said. “Every day people ask me, ‘Are there any evidence-based strategies?’ And so far I have to say, every day, ‘No.’ I hate to say it, but it’s kind of like every patient is on their own. They’re trying different things because they can’t wait. There is an imperative to help them.”

At the end of July, the National Institutes of Health launched phase 2 clinical trials to evaluate at least four new treatments for long COVID, all part of the RECOVER initiative. By then, Mr. Lewis, who believes his myalgic encephalomyelitis/chronic fatigue syndrome was triggered by the virus, had made plans to try an alternative, experimental therapy.

“My hope is that it will fix me,” he said. “I’m excited about those kinds of hard-hitting infusion, immunological treatment.”

As for the JAMA study, he didn’t allow himself to get excited when it was released, a function of his experience as a data analyst and long COVID patient.

“I don’t think it moves the needle much yet,” he said. “It’s the first study, and we shouldn’t expect much from the first pieces of data to come out of that. If they keep following that cohort and go deeper and deeper, they’re going to find some interesting stuff that will lead to treatments.”

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

A growing number of long COVID patients, denied disability benefits despite being unable to work, are turning to the courts for legal relief.

At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.

But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.

“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”

As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.

“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”

The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.

Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.

But even in the courts, many encounter delays and hurdles to resolution.

In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.

His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”

Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.

Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.

He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.

Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.

“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”

Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.

Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.

Representatives of Reliance Standard didn’t respond to a request for comment.

The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.

Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.

“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”

Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.

For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.

Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.

Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.

All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.

“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”

Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.

Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.

“I have done letter upon letter of appeal to disability insurance companies,” she said.

Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.

“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.

“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”

A version of this article appeared on Medscape.com.

A growing number of long COVID patients, denied disability benefits despite being unable to work, are turning to the courts for legal relief.

At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.

But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.

“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”

As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.

“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”

The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.

Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.

But even in the courts, many encounter delays and hurdles to resolution.

In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.

His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”

Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.

Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.

He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.

Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.

“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”

Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.

Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.

Representatives of Reliance Standard didn’t respond to a request for comment.

The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.

Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.

“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”

Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.

For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.

Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.

Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.

All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.

“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”

Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.

Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.

“I have done letter upon letter of appeal to disability insurance companies,” she said.

Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.

“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.

“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”

A version of this article appeared on Medscape.com.

A growing number of long COVID patients, denied disability benefits despite being unable to work, are turning to the courts for legal relief.

At least 30 lawsuits have been filed seeking legal resolution of disability insurance claims, according to searches of court records. In addition, the Social Security Administration said it has received about 52,000 disability claims tied to SARS-CoV-2 infections, which represents 1% of all applications.

But legal experts say those cases may not reflect the total number of cases that have gone to court. They note many claims are initially dismissed and are not appealed by claimants.

“With this system, they deny two-thirds of initial applications, then people who appeal get denied almost 90% of the time, and then they can appeal before a judge,” said Kevin LaPorte, a Social Security disability attorney at LaPorte Law Firm in Oakland, Calif. “What happens next doesn’t have a lot of precedent because long COVID is a mass disabling event, and we haven’t seen that many of these cases get all the way through the legal system yet.”

As a result, the exact number of long COVID disability claims and the number of these cases going to court isn’t clear, he said.

“It can take a year or more for cases to get to court, and even longer to reach resolution,” Mr. LaPorte added. “I suspect the few cases we’ve heard about at this point are going to be the tip of the iceberg.”

The process is convoluted and can drag on for months with multiple denials and appeals along the way. Many disabled workers find their only recourse is to take insurers to court.

Long COVID patients typically apply for disability benefits through private insurance or Social Security. But the process can drag on for months, so many find their only recourse is to take insurers to court, according to legal experts.

But even in the courts, many encounter delays and hurdles to resolution.

In one of the first federal lawsuits involving long COVID disability benefits, William Abrams, a trial and appellate attorney and active marathon runner, sued Unum Life Insurance seeking long-term disability income. Symptoms included extreme fatigue, brain fog, decreased attention and concentration, and nearly daily fevers, causing him to stop working in April 2020.

His diagnosis wasn’t definitive. Three doctors said he had long COVID, and four said he had chronic fatigue syndrome. Unum cited this inconsistency as a rationale for rejecting his claim. But the court sided with Mr. Abrams, granting him disability income. The court concluded: “Unum may be correct that [the plaintiff] has not been correctly diagnosed. But that does not mean he is not sick. If [the plaintiff’s] complaints, and [the doctor’s] assessments, are to be believed, [the plaintiff] cannot focus for more than a few minutes at a time, making it impossible for [the plaintiff] to perform the varied and complex tasks his job requires.”

Unum said in an emailed statement that the company doesn’t comment on specific claims as a matter of policy, adding that its total payouts for disability claims from March 2020 to February 2022 were 35% higher than prepandemic levels. “In general, disability and leave claims connected to COVID-19 have been primarily short-term events with the majority of claimants recovering prior to completing the normal qualification period for long-term disability insurance,” Unum said.

Mr. Abrams prevailed in part because he had detailed documentation of the numerous impairments that eventually required him to stop work, said Michelle Roberts of Roberts Disability Law in Oakland, Calif.

He submitted videos of himself taking his temperature to prove he had almost daily fevers, according to court records. He underwent neuropsychological testing, which found learning deficiencies and memory deficits.

Mr. Abrams also submitted statements from a colleague who worked with him on a complex technology patent case involving radiofrequency identification. Before he got COVID, Mr. Abrams “had the analytical ability, legal acumen, and mental energy to attack that learning curve and get up to speed very rapidly,” according to court records.

“The court focused on credulity.” Ms. Roberts said. “There was all this work to be done to show this person was high functioning and ran marathons and worked in an intense, high-pressure occupation but then couldn’t do anything after long COVID.”

Documentation was also crucial in another early federal long COVID disability lawsuit that was filed in 2022 on behalf of Wendy Haut, an educational software sales representative in California who turned to the courts seeking disability income through her company’s employee benefits plan.

Several of Ms. Haut’s doctors documented a detailed list of long COVID symptoms, including “profound fatigue and extreme cognitive difficulties,” that they said prevented her from working as a sales representative or doing any other type of job. A settlement agreement in June 2022 required Reliance Standard Life Insurance to pay Ms. Haut long-term disability benefits, including previously unpaid benefits, according to a report by the advocacy group Pandemic Patients.

Representatives of Reliance Standard didn’t respond to a request for comment.

The growing number of workers being sidelined by long COVID makes more claims and more court cases likely. Right now, an estimated 16 million working-age Americans aged 18-65 years have long COVID, and as many as 4 million of them can’t work, according to a July 2023 Census Bureau report.

Uncertainty about the volume of claims in the pipeline is part of what’s driving some insurers to fight long COVID claims, Ms. Roberts said. Another factor is the lack of clarity around how many years people with long COVID may be out of work, particularly if they’re in their 30s or 40s and might be seeking disability income until they reach retirement age.

“Doctors are not always saying that this person will be permanently disabled,” Ms. Roberts said. “If this person doesn’t get better and they’re disabled until retirement age, this could be a payout in the high six or seven figures if a person is very young and was a very high earner.”

Insurance companies routinely deny claims that can’t be backed up with objective measures, such as specific lab test results or clear findings from a physical exam. But there are steps that can increase the odds of a successful claim for long COVID disability benefits, according to New York–based law firm Hiller.

For starters, patients can document COVID test results, and if testing wasn’t conducted, patients can detail the specific symptoms that led to this diagnosis, Hiller advises. Then patients can keep a daily symptom log at home that run lists all of the specific symptoms that occur at different times during the day and night to help establish a pattern of disability. These logs should provide specific details about every job duty patients have and exactly how specific symptoms of long COVID interfere with these duties.

Even though objective testing is hard to come by for long COVID, people should undergo all the tests they can that may help document the frequency or severity of specific symptoms that make it impossible to carry on with business as usual at work, Hiller advises. This may include neuropsychological testing to document brain fog, a cardiopulmonary exercise test to demonstrate chronic fatigue and the inability to exercise, or a tilt table test to measure dizziness.

Seeking a doctor’s diagnosis can be key to collecting disability payments, in or out of court.

All of this puts a lot of pressure on doctors and patients to build strong cases, said Jonathan Whiteson, MD, codirector of the NYU Langone Health post-COVID care program in New York. “Many physicians are not familiar with the disability benefit paperwork, and so this is a challenge for the doctors to know how to complete and to build the time into their highly scheduled days to take the time needed to complete.

“It’s also challenging because most of the disability benefit forms are ‘generic’ and do not ask specific questions about COVID disability,” Dr. Whiteson added. “It can be like trying to drive a square peg into a round hole.”

Still, when it comes to long COVID, completing disability paperwork is increasingly becoming part of standard care, along with managing medication, rehabilitation therapies, and lifestyle changes to navigate daily life with this illness, Dr. Whiteson noted.

Monica Verduzco-Gutierrez, MD, chair of rehabilitation medicine and director of the Post-COVID-19 Recovery Clinic at the University of Texas Health Science Center, San Antonio, agreed with this assessment.

“I have done letter upon letter of appeal to disability insurance companies,” she said.

Some doctors, however, are reluctant to step up in such cases, in part because no standard diagnostic guidelines exist for long COVID and because it can be frustrating.

“This is the work that is not paid and causes burnout in physicians,” Dr. Verduzco-Gutierrez said. “The paperwork, the fighting with insurance companies, the resubmission of forms for disability all to get what your patient needs – and then it gets denied.

“We will keep doing this because our patients need this disability income in order to live their lives and to afford what they need for recovery,” said Dr. Verduzco-Gutierrez. “But at some point something has to change because this isn’t sustainable.”

A version of this article appeared on Medscape.com.

Enrollment is opening for four clinical trials that will evaluate new treatments for long COVID, the National Institutes of Health announced at a media briefing today. Additional clinical trials to test at least seven more treatments are expected to launch in the coming months, officials said.

The trials are part of the NIH’s research effort known as the Researching COVID to Enhance Recovery (RECOVER) Initiative. In December 2020, Congress approved $1.15 billion for the NIH to research and test treatments for long COVID. The new clinical trials are in phase 2 and will test safety and effectiveness.

“The condition affects nearly all body systems and presents with more than 200 symptoms,” said Walter J. Koroshetz, MD, director of the NIH National Institute of Neurological Disorders and Stroke and colead of the RECOVER Initiative. How many people have long COVID is uncertain, he told attendees at the briefing. “The answer kind of depends on how you define the problem and also what variant caused it. The incidence was higher in Delta.” Some estimates suggest that 5%-10% of those infected develop long COVID. “I don’t think we have solid numbers, as it’s a moving target,” Dr. Koroshetz said.

Patients with long COVID have grown increasingly frustrated at the lack of effective treatments. Some doctors have turned to off-label use of some drugs to treat them.

The four trials include the following:

• RECOVER-VITAL will focus on a treatment for viral persistence, which can occur if the virus lingers and causes the immune system to not work properly. One treatment will test a longer dose regimen of the antiviral Paxlovid (nirmatrelvir and ritonavir), which is currently used to treat mild to moderate COVID to halt progression to severe COVID.
• RECOVER-NEURO will target treatments for symptoms such as brain fog, memory problems, and attention challenges. Among the potential treatments are a program called BrainHQ, which provides Web-based training, and PASC-Cognitive Recovery (post-acute sequelae of COVID), a Web-based program developed by Mount Sinai Health System in New York. Also being tested is a direct current stimulation program to improve brain activity.
• RECOVER-SLEEP will evaluate treatments for sleep problems, which can include daytime sleepiness and other problems. According to Dr. Koroshetz, melatonin, light therapy, and an educational coaching system are among the treatments that will be studied.
• RECOVER-AUTONOMIC will evaluate treatments to address symptoms linked with problems of the autonomic nervous system. The first trial will target postural orthostatic tachycardia syndrome (POTS), which can include irregular heartbeat, fatigue, and dizziness. A treatment for immune disease and a drug currently used to treat chronic heart failure will be tested.

Timelines

The first trial, on viral persistence, has launched, said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute, the clinical trials data coordinating center for the trials. “We are actively working to launch the second on cognitive dysfunction.” The sleep and autonomic trials will launch in the coming months, she said. Also planned is a trial to study exercise intolerance, which is reported by many with long COVID.

Information on how to join long COVID trials is available here.

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

Enrollment is opening for four clinical trials that will evaluate new treatments for long COVID, the National Institutes of Health announced at a media briefing today. Additional clinical trials to test at least seven more treatments are expected to launch in the coming months, officials said.

The trials are part of the NIH’s research effort known as the Researching COVID to Enhance Recovery (RECOVER) Initiative. In December 2020, Congress approved $1.15 billion for the NIH to research and test treatments for long COVID. The new clinical trials are in phase 2 and will test safety and effectiveness.

“The condition affects nearly all body systems and presents with more than 200 symptoms,” said Walter J. Koroshetz, MD, director of the NIH National Institute of Neurological Disorders and Stroke and colead of the RECOVER Initiative. How many people have long COVID is uncertain, he told attendees at the briefing. “The answer kind of depends on how you define the problem and also what variant caused it. The incidence was higher in Delta.” Some estimates suggest that 5%-10% of those infected develop long COVID. “I don’t think we have solid numbers, as it’s a moving target,” Dr. Koroshetz said.

Patients with long COVID have grown increasingly frustrated at the lack of effective treatments. Some doctors have turned to off-label use of some drugs to treat them.

The four trials include the following:

• RECOVER-VITAL will focus on a treatment for viral persistence, which can occur if the virus lingers and causes the immune system to not work properly. One treatment will test a longer dose regimen of the antiviral Paxlovid (nirmatrelvir and ritonavir), which is currently used to treat mild to moderate COVID to halt progression to severe COVID.
• RECOVER-NEURO will target treatments for symptoms such as brain fog, memory problems, and attention challenges. Among the potential treatments are a program called BrainHQ, which provides Web-based training, and PASC-Cognitive Recovery (post-acute sequelae of COVID), a Web-based program developed by Mount Sinai Health System in New York. Also being tested is a direct current stimulation program to improve brain activity.
• RECOVER-SLEEP will evaluate treatments for sleep problems, which can include daytime sleepiness and other problems. According to Dr. Koroshetz, melatonin, light therapy, and an educational coaching system are among the treatments that will be studied.
• RECOVER-AUTONOMIC will evaluate treatments to address symptoms linked with problems of the autonomic nervous system. The first trial will target postural orthostatic tachycardia syndrome (POTS), which can include irregular heartbeat, fatigue, and dizziness. A treatment for immune disease and a drug currently used to treat chronic heart failure will be tested.

Timelines

The first trial, on viral persistence, has launched, said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute, the clinical trials data coordinating center for the trials. “We are actively working to launch the second on cognitive dysfunction.” The sleep and autonomic trials will launch in the coming months, she said. Also planned is a trial to study exercise intolerance, which is reported by many with long COVID.

Information on how to join long COVID trials is available here.

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

Enrollment is opening for four clinical trials that will evaluate new treatments for long COVID, the National Institutes of Health announced at a media briefing today. Additional clinical trials to test at least seven more treatments are expected to launch in the coming months, officials said.

The trials are part of the NIH’s research effort known as the Researching COVID to Enhance Recovery (RECOVER) Initiative. In December 2020, Congress approved $1.15 billion for the NIH to research and test treatments for long COVID. The new clinical trials are in phase 2 and will test safety and effectiveness.

“The condition affects nearly all body systems and presents with more than 200 symptoms,” said Walter J. Koroshetz, MD, director of the NIH National Institute of Neurological Disorders and Stroke and colead of the RECOVER Initiative. How many people have long COVID is uncertain, he told attendees at the briefing. “The answer kind of depends on how you define the problem and also what variant caused it. The incidence was higher in Delta.” Some estimates suggest that 5%-10% of those infected develop long COVID. “I don’t think we have solid numbers, as it’s a moving target,” Dr. Koroshetz said.

Patients with long COVID have grown increasingly frustrated at the lack of effective treatments. Some doctors have turned to off-label use of some drugs to treat them.

The four trials include the following:

• RECOVER-VITAL will focus on a treatment for viral persistence, which can occur if the virus lingers and causes the immune system to not work properly. One treatment will test a longer dose regimen of the antiviral Paxlovid (nirmatrelvir and ritonavir), which is currently used to treat mild to moderate COVID to halt progression to severe COVID.
• RECOVER-NEURO will target treatments for symptoms such as brain fog, memory problems, and attention challenges. Among the potential treatments are a program called BrainHQ, which provides Web-based training, and PASC-Cognitive Recovery (post-acute sequelae of COVID), a Web-based program developed by Mount Sinai Health System in New York. Also being tested is a direct current stimulation program to improve brain activity.
• RECOVER-SLEEP will evaluate treatments for sleep problems, which can include daytime sleepiness and other problems. According to Dr. Koroshetz, melatonin, light therapy, and an educational coaching system are among the treatments that will be studied.
• RECOVER-AUTONOMIC will evaluate treatments to address symptoms linked with problems of the autonomic nervous system. The first trial will target postural orthostatic tachycardia syndrome (POTS), which can include irregular heartbeat, fatigue, and dizziness. A treatment for immune disease and a drug currently used to treat chronic heart failure will be tested.

Timelines

The first trial, on viral persistence, has launched, said Kanecia Zimmerman, MD, a principal investigator at the Duke Clinical Research Institute, the clinical trials data coordinating center for the trials. “We are actively working to launch the second on cognitive dysfunction.” The sleep and autonomic trials will launch in the coming months, she said. Also planned is a trial to study exercise intolerance, which is reported by many with long COVID.

Information on how to join long COVID trials is available here.

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

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

Doctors who treat patients with long COVID, hampered by a lack of federally approved treatments, are turning to off-label use of drugs designed for addiction, diabetes, and other conditions.

Those with long COVID for years now are engaging in robust online conversations about a range of treatments not formally approved by the Food and Drug Administration for the condition, reporting good and bad results.

High on the current list: low-dose naltrexone (LDN). A version of drug developed to help addicts has been shown to help some long COVID patients.

But evidence is building for other treatments, many of them targeted to treat brain fog or one of the other long-term symptoms in individuals 3 months or more after acute COVID infection.

Some patients are taking metformin, which studies have found to be effective at lowering long COVID risk. Paxlovid is being tested for long COVID.  Antivirals are also on the list.

Alba Azola, MD, said she has treated long COVID patients with brain fog and dizziness who have postural orthostatic tachycardia syndrome (POTS).

Dr. Azola said she asked the staff at Johns Hopkins Medicine in Baltimore, where she is a rehabilitation specialist, to teach her how to treat the condition. Since there is no approved treatment for POTS, that meant using off-label drugs, she said. 

“It was super scary as a provider to start doing that, but my patients were suffering so much,” she  said, noting the wait for patients to get into the POTS clinic at Hopkins was 2 years.

Dr. Azola was the lead author on guidelines published by the American Academy of Physical Medicine and Rehabilitation (AAPM&R) last September on how to treat autonomic dysfunction, a common symptom of long COVID. 

The guidelines she helped write include drugs designed for blood pressure – such as midodrine – and steroids.

Dr. Azola noted the medications are prescribed on a case-by-case basis because the same drug that works for one patient may have awful side effects for another patient, she said. At the same time, some of these drugs have helped her patients go back to living relatively normal lives.

The first time JD Davids of Brooklyn, N.Y., took LDN, it was for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and he couldn’t tolerate it. He had nightmares. But when he took it for long COVID, he started out at a low dose and worked his way up, at his doctor’s advice. 

“It’s been a game-changer,” said Mr. Davids, cofounder of Long COVID Justice, an activist group. He has ME/CFS and several other chronic conditions, including long COVID. But, since he started taking LDN for long COVID, Mr. Davids said he has more energy and less pain. 

Technically, evidence is required to show off-label drug use could be effective in treating conditions for which the drug is not formally approved. Research suggests that 20%-30% of drugs are prescribed off-label.

No formal data exist on how widespread the use of off-label drugs for long COVID may be. But LDN is a major topic of discussion on public patient groups on Facebook. 

A recent study in The Lancet Infectious Diseases suggested that the diabetes drug metformin could be helpful. (The same study found no benefit from ivermectin, a drug since dismissed as a possible COVID treatment.)

Patients who testified at a virtual FDA hearing on drug development in April reported using vitamins, herbal supplements, over-the-counter medications and off-label drugs such as gabapentin and beta-blockers. Both of those drugs were on a list of potential treatments published in a January Nature Review article, along with LDN and Paxlovid.

Currently, Paxlovid is approved for acute COVID, and is in clinical trials as a treatment for long COVID as part of the federal government’s RECOVER Initiative. While only small studies of LDN have been conducted for long COVID, doctors are already prescribing the treatment. Mr. Davids said his primary care doctor recommended it.

Some doctors, such as Michael Peluso, MD, are comparing the trend to the early days of the AIDS epidemic, when the federal government was slow to recognize the viral disease. Patients banded together to protest and gain access to experimental treatments. 

Dr. Peluso, who treats long COVID patients at the University of California, San Francisco, said that without any approved treatment, patients are turning to one another to find out what works.

“A lot of people experiencing long COVID are looking for ways to feel better now, rather than waiting for the science or the guidelines to catch up,” he said in an interview.

In some cases, the drugs are backed by small studies, he said. 

“While we still need clinical trials to prove what will work, the drugs tested in these trials are also being informed by anecdotes shared by patients,” Dr. Peluso said.

Gail Van Norman, MD, of the University of Washington, Seattle, also said the long COVID situation today is reminiscent of the AIDS movement, which was “one of the times in history where we saw a real response to patient advocacy groups in terms of access to drugs.” Since then, the FDA has set up multiple programs to expand access to experimental drugs, added Dr. Van Norman, author of a recent study on off-label drug use.

But off-label use needs to be supervised by a physician, she and others said. Many patients get their information from social media, which Dr. Van Norman sees as a double-edged sword. Patients can share information, do their own research online, and alert practitioners to new findings, she said. But social media also promotes misinformation.

“People with no expertise have the same level of voice, and they are magnified,” Dr. Van Norman said.

The FDA requires doctors to have some evidence to support off-label use, she said. Doctors should talk to patients who want to try-off label drugs about what has been studied and what has not been studied.

“If I had [long COVID], I would be asking questions about all these drugs,” Dr. Van Norman said.

Mr. Davids has been asking questions like this for years. Diagnosed in 2019 with ME/CFS, he developed long COVID during the pandemic. Once he began started taking LDN, he started feeling better.

As someone with multiple chronic illnesses, Mr. Davids has tried a lot of treatments – he’s currently on two intravenous drugs and two compounded drugs, including LDN. But when his doctor first suggested it, he was wary. 

“I’ve worked with her to help increase the dosage slowly over time,” he said. “It’s very important for many people to start low and slow and work their way up.”

He hears stories of people who can’t get it from their physicians. Some, he said, think it may be because of the association of the drug with opioid abuse. 

Mr. Davids said long COVID patients have no other choice but to turn to alternative treatments. 
 

“I think we’ve been ill-served by our research establishment,” he said. “It is not set up for complex chronic conditions.”

Mr. Davids said he doesn’t know if LDN helps with underlying conditions or treats the symptoms – such as pain and fatigue – that keep him from doing things such as typing. 

“My understanding is that it may be doing both,” he said. “I sure am happy that it allows me to do things like keep my job.”

Dr. Azola and others said patients need to be monitored closely if they are taking an off-label drug. She recommends primary care doctors become familiar with them so they can offer patients some relief.

“It’s about the relationship between the patient and the provider and the provider being comfortable,” she said. “l was very transparent with my patients.”
 

A version of this article appeared on Medscape.com.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.

Experience with long COVID has shone a spotlight on persistent Lyme disease and other often debilitating chronic illnesses that follow known or suspected infections – and on the urgent need for a common and well-funded research agenda, education of physicians, growth of multidisciplinary clinics, and financially supported clinical care.

“We critically need to understand the epidemiology and pathogenesis of chronic symptoms, and identify more effective ways to manage, treat, and potentially cure these illnesses,” Lyle Petersen, MD, MPH, director of the division of vector-borne diseases at the Centers for Disease Control and Prevention, said at the start of a 2-day National Academies of Science, Engineering, and Medicine (NASEM) workshop, “Toward a Common Research Agenda in Infection-Associated Chronic Illnesses.”

Thinking about infection-associated chronic illnesses as an entity – one predicated on commonalities in chronic symptoms and in leading hypotheses for causes – represents a paradigm shift that researchers and patient advocates said can avoid research redundancies and is essential to address what the NASEM calls an overlooked, growing public health problem.

An estimated 2 million people in the United States are living with what’s called posttreatment Lyme disease (PTLD) – a subset of patients with persistent or chronic Lyme disease – and an estimated 1.7-3.3 million people in the United States have diagnoses of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). More than 700,000 people are living with multiple sclerosis. And as of January 2023, 11% of people in the United States reported having long COVID symptoms; the incidence of long COVID is currently estimated at 10%-30% of nonhospitalized cases of COVID-19.

These illnesses “have come under one umbrella,” said Avindra Nath, MD, clinical director of the National Institute of Neurologic Disorders and Stroke (NINDS), Bethesda, Md.

Dr. Nath

Persistent infection, viral reactivation

RNA viral infections can lead to persistent inflammation and dysregulated immunity, with or without viral persistence over time, Timothy J. Henrich, MD, MMSc, associate professor of medicine at the University of California, San Francisco, said in a keynote address.

Research on Ebola survivors has documented long-lasting inflammation and severe immune dysfunction 2 years after infection, for instance. And it’s well known that HIV-1 leads to aberrant immune responses, inflammation, and organ damage despite antiretroviral therapy, said Dr. Henrich, who leads a laboratory/research group that studies approaches to HIV-1 cure and PET-based imaging approaches to characterize viral reservoirs and immune sequelae.

Viral persistence, which can be difficult to measure, has also been documented in Ebola survivors. And in patients living with HIV-1, HIV-1 RNA and protein expression have been shown to persist, again despite antiretroviral therapy. The UCSF Long-Term Immunological Impact of Novel Coronavirus (LIINC) study, for which Dr. Henrich is the principal investigator, found spike RNA in colorectal tissue more than 22 months post COVID, and other research documented viral protein in gut tissue for up to 6 months, he said.

“I think we’re appreciating now, in at least the scientific and treatment community, that there’s a potential for ‘acute’ infections to exhibit some degree of persistence leading to clinical morbidity,” said Dr. Henrich, one of several speakers to describe reports of pathogen persistence. Regarding long COVID, its “etiology is likely heterogeneous,” he said, but persistence of SARS-CoV-2 “may lay behind” other described mechanisms, from clotting/microvascular dysfunction to inflammation and tissue damage to immune dysregulation.

Reactivation of existing latent viral infections in the setting of new acute microbial illness may also play an etiologic role in chronic illnesses, Dr. Henrich said. Epstein-Barr virus (EBV) reactivation has been shown in some studies, including their UCSF COVID-19 cohort, to be associated with long COVID.

“Physicians have been trained to be skeptical about the role [of latent viral infections],” Michael Peluso, MD, an infectious disease physician and assistant professor at UCSF, said during a talk on viral reactivation. This skepticism needs to be “reexamined and overcome,” he said.

Herpesviruses have frequently been associated with ME/CFS, he noted. And evidence of a strong association between EBV and multiple sclerosis came recently from a prospective study of 10 million military recruits that found a 32-fold increased risk of MS after EBV infection but no increase after infection with other viruses, Dr. Peluso and Dr. Henrich both noted.
 

Research needs, treatment trials

Research needs are vast: The need to learn more about the mechanisms of pathogen persistence and immune evasion, for instance, and the need for more biomarker studies, more imaging studies and tissue analyses, more study of microbiome composition and activity, and continued development and application of metagenomic next-generation sequencing.

Workshop participants also spoke of the need to better understand the molecular mimicry that can occur between pathogen-produced proteins and self-antigens, for instance, and the effects of inflammation and infection-related immune changes on neuronal and microglial function in the brain.

“We should perform similar forms of analysis [across] patients with different infection-associated chronic conditions,” said Amy Proal, PhD, president of the PolyBio Research Foundation, which funds research on infection-associated chronic infections. And within individual conditions and well-characterized study groups “we should perform many different forms of analysis … so we can define endotypes and get more solid biomarkers so that industry [will have more confidence] to run clinical trials.”

In the meantime, patients need fast-moving treatment trials for long COVID, long Lyme, and other infection-associated chronic illnesses, speakers emphasized. “We all agree that treatment trials are overdue,” said the NINDS’ Dr. Nath. “We can’t afford to wait for another decade until we understand all the mechanisms, but rather we can do clinical trials based on what we understand now and study the pathophysiology in the context of the clinical trials.”

Just as was done with HIV, said Steven G. Deeks, MD, professor of medicine at UCSF, researchers must “practice experimental medicine” and select pathways and mechanisms of interest, interrupt those pathways in a controlled manner, and assess impact. “Much of this can be done by repurposing existing drugs,” he said, like antivirals for persistent viral infection, EBV-directed therapies for EBV reactivation, anti-inflammatory drugs for inflammation, B–cell-directed therapies for autoantibodies, and antiplatelet drugs for microvascular disease.

When done correctly, he said, such “probe” studies can deepen mechanistic understandings, lead to biomarkers, and provide proof-of-concept that “will encourage massive investment in developing new therapies” for long COVID and other infection-associated chronic illnesses.

Trials of treatments for long COVID “are starting, so I’m optimistic,” said Dr. Deeks, an expert on HIV pathogenesis and treatment and a principal investigator of the Researching COVID to Enhance Recovery (RECOVER) study. Among the trials: A study of intravenous immunoglobulin (IVIG) for neurologic long COVID; a study of an anti-SARS-CoV-2 monoclonal antibody that can deplete tissue/cellular reservoirs of viral particles (replicating or not); and a study evaluating baricitinib (Olumiant), a Janus kinase inhibitor, for neurocognitive impairment and cardiopulmonary symptoms of long COVID.

Alessio Fasano, MD, professor of pediatrics at Harvard Medical School and professor of nutrition at the Harvard T.H. Chan School of Public Health, Boston, described at the workshop how he began investigating the use of larazotide acetate – an inhibitor of the protein zonulin, which increases intestinal permeability – in children with COVID-19 Multisystem Inflammatory Syndrome (MIS-C) after learning that SARS-CoV-2 viral particles persist in the gastrointestinal tract, causing dysbiosis and zonulin upregulation.

In an ongoing phase 2, double-blind, placebo-controlled trial, the agent thus far has expedited the resolution of gastrointestinal symptoms and clearance of spike protein from the circulation, he said. A phase 2 trial of the agent for pediatric patients with long COVID and SARS-CoV-2 antigenemia is underway. “What if we were to stop [chains of events] by stopping the passage of elements from the virus into circulation?’ he said.

In the realm of Lyme disease, a recently launched Clinical Trials Network for Lyme and Other Tick-Borne Diseases has awarded pilot study grants to evaluate treatments aimed at a variety of possible disease mechanisms that, notably, are similar to those of other chronic illnesses: persistence of infection or remnants of infection, immune dysregulation and autoimmune reactions, neural dysfunction, and gut microbiome changes. (Microclots and mitochondrial dysfunction have not been as well studied in Lyme.)

Current and upcoming studies include evaluations of transcutaneous auricular vagus nerve stimulation for those with persistent Lyme fatigue, transcranial direct current stimulation with cognitive retraining for Lyme brain fog, and tetracycline for PTLD, said Brian Fallon, MD, MPH, professor of clinical psychiatry at Columbia University, New York, who directs the Lyme & Tick-Borne Diseases Research Center and the coordinating center of the new network.

Columbia University Irving Medical Center

Calls for a new NIH center and patient involvement

Patients and patient advocacy organizations have played a vital role in research thus far: They’ve documented post-COVID symptoms that academic researchers said they would not otherwise have known of. Leaders of the Patient-Led Research Collaborative have coauthored published reviews with leading long COVID experts. And patients with tick-borne illnesses have enrolled in the MyLymeData patient registry run by LymeDisease.org, which has documented patient-experienced efficacy of alternative treatments and described antibiotic responders and nonresponders.

At the workshop, they shared findings alongside academic experts, and researchers called for their continued involvement. “Patient engagement at every step of the research process is critical,” Dr. Nath said.

“We need to ensure that research is reflective of lived experiences … and [that we’re] accelerating clinical trials of therapeutics that are of priority to the patient community,” said Lisa McCorkell, cofounder of the long COVID-focused Patient-Led Research Collaborative.

Ms. McCorkell also called for the creation of an office for infection-associated chronic illnesses in the NIH director’s office. Others voiced their support. “I think it’s a great idea to have an NIH center for infection-associated chronic illnesses,” said Dr. Fallon. “I think it would have a profound impact.”

The other great need, of course, is funding. “We have ideas, we have drugs that can be repurposed, we have a highly informed and engaged community that will enroll in and be retained in studies, and we have outcomes we can measure,” Dr. Deeks said. “What we’re missing is industry engagement and funding. We need massive engagement from the NIH.”
 

Real-world treatment needs

In the meantime, patients are seeking treatment, and “clinicians need to have uncertainty tolerance” and try multiple treatments simultaneously, said David Putrino, PT, PhD, director of rehabilitation innovation for the Mount Sinai Health System and professor of rehabilitation and human performance at the Icahn School of Medicine at Mount Sinai, New York. He oversees a multidisciplinary hybrid clinical care research center that has seen over 1,500 patients with long COVID and is beginning to see patients with other infection-associated chronic illnesses.

Claudia Paul

It’s a model that should be replicated to help fill the “enormous unmet clinical need” of patients with infection-associated chronic illness, said Peter Rowe, MD, professor of pediatrics at the Johns Hopkins School of Medicine and an expert on ME/CFS. And “as we request [more research funding], we will also need [financial] support for clinical care,” he emphasized, to provide equitable access for patients and to attract treating physicians.

Moreover, said Linda Geng, MD, PhD, the culture of stigma needs to change. Right now, patients with long COVID often feel dismissed not only by friends, families, and coworkers, but by clinicians who find it find it hard “to grasp that this is real and a biological condition.”

And it’s not just conditions such as long COVID that are stigmatized, but treatments as well, she said. For instance, some clinicians view low-dose naltrexone, a treatment increasingly being used for inflammation, with suspicion because it is used for opioid use disorder and alcohol use disorder – or because the “low-dose” label summons mistrust of homeopathy. “Even with therapies, there are preconceived notions and biases,” said Dr. Geng, cofounder and codirector of the Stanford (Calif.) Long COVID program.

“What almost killed me,” said Meghan O’Rourke, who has ongoing effects from long-undiagnosed tick-borne illness, “was the invisibility of the illness.” Ms. O’Rourke teaches at Yale University and is the author of “The Invisible Kingdom: Reimagining Chronic Illness.”

Teaching young physicians about these illnesses would help, she and others said. During a question and answer session, Dr. Putrino shared that the Icahn School of Medicine has recently committed to “create a complex chronic illness medical curriculum” that will impact medical education from the first year of medical school through residencies. Dr. Putrino said his team is also working on materials to help other clinics develop care models similar to those at his Mount Sinai clinic.

The NASEM workshop did not collect or require disclosures of its participants.