Sara Novak

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

When Ezra Spier was diagnosed with long COVID in late 2022, his main symptom, postexertional malaise, caused fatigue so severe that it forced him to quit his job as a technology entrepreneur. Since then, it’s been a tough road for Spier, 37, who said he wouldn’t wish his hellish condition on anyone. 

Last spring, he enrolled in a clinical trial of a new long COVID therapy at Stanford University, and he’s about to start another at the University of California, San Francisco. 

For Spier, who lives in Oakland, California, being part of the clinical trials connected him with people dealing with similar health issues while also moving the needle toward better treatments for everyone. Yet many potential participants are unaware that these clinical trials exist. Clinical trial researchers also express frustration over the challenge of enrolling participants.

That’s why Spier created a new website to help match long COVID patients with clinical trials that can help.

“I wanted a way to make long COVID clinical trials more accessible to the general public,” he said. Spier’s website, aptly named Long Covid Studies, launched in March. The site already includes details from about 550 trials globally and, in the future, will include many more.
 

It’s Not the Number of Studies, It’s Navigating Them

In all, nearly 9300 long COVID trials are listed on ClinicalTrials.gov. But many patients find the site difficult to navigate, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City. He said Spier’s website helps make trials easier for patients to manage in ways that remove the enrollment challenges.

“Ezra’s platform pulls data from ClinicalTrials.gov and puts it into a space that’s much easier for patients to manage,” said Dr. Putrino. The site only includes the most relevant information, such as the study location, eligibility, and purpose and how to sign up. 

Another of Spier’s goals is to make the process easier for patients who are already marginalized and often excluded from the healthcare system. Long COVID disproportionately impacts people in minority ethnic groups and women, as well as those who are impoverished or live in rural areas. 

According to the National Institutes of Health (NIH), 1 in 4 patients with severe long COVID-19 are Black or Hispanic whereas only 1 in 7 are White. Yet participation by White persons in clinical trials is much higher overall: 77% of participants are White, compared with only 14% for Black persons and 15% for Hispanic persons. Without more balanced representation, research becomes skewed and less accurate, said Grace McComsey, MD, who leads one of the 15 nationwide long COVID centers funded by the federal RECOVER (Researching COVID to Enhance Recovery) Initiative in Cleveland. 

Websites that are easier for the layperson to access would allow for wider participation, said McComsey.
 

Too Many Barriers to Entry

A study published in the Journal of Applied Gerontology found that transportation plays an outsized role in influencing study participation, which may also lead to less diverse participation.

Decentralized trials — in which participants receive therapy at home — also make enrolling in clinical trials easier for marginalized patients and those too sick to make it to a research center, said Dr. Putrino. Research published recently in The American Journal of Medicine demonstrated that for many patients, remote studies are the future of COVID research. The study, focusing on the efficacy of Paxlovid, recruited patients living in the 48 contiguous US states. Participation was entirely remote. 

“We need to have more consideration for bedbound and housebound patients in our research,” said Dr. Putrino. “Some people don’t have the ability to show up to a prestigious university to take part in an academic trial.”

Dr. Putrino and colleagues at Yale School of Medicine’s Yale COVID Recovery Study plan to release a paper in the near future on the methodology for running decentralized or remote studies that could provide guidance for researchers elsewhere. 

Decentralized studies serve a larger audience, but they’re also more expensive and cost has plagued long COVID research from the start, said Michael Peluso, MD, an assistant research professor of infectious medicine at UCSF School of Medicine, University of California, San Francisco. 

“You need to have a staff in place that’s trained to do home visits in order to conduct remote trials,” Dr. Peluso said, adding that his biggest challenge has been connecting patients to appropriate clinical trials. 

Individual eligibility has been an ongoing issue. For example, Dr. Peluso’s current trials are testing monoclonal antibodies — antibodies produced by cloning unique white blood cells to target viral persistence, which is thought to be a cause of long COVID. Only patients who were infected with certain variants of acute COVID are eligible because of the antibodies needed to target SARS-CoV-2 spike proteins. 

“This can lead to a lot of frustration among patients who might think they can participate, but aren’t eligible,” said Dr. Peluso.
 

Long Fight for Better Long COVID Research

For Spier, one of the hardest parts of his health issues and lack of energy is that they have sharply curtailed his social interactions with friends and colleagues. 

He has channeled his energies into researching new treatments that could potentially improve his symptoms. That research is partly what drove him to create the Long Covid Studies website.

His goal is still to help others with long COVID find trials that can improve their symptoms as well. The more people who participate, the closer scientists will come to providing effective treatments for everyone, he said.

“For all my frustrations, we’re still at the forefront of science globally,” he said. “And if we have the level of funding the NIH is equipped to provide, we can show the world what’s possible with long COVID research.”

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

Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Four years ago in the spring of 2020, physicians and patients coined the term “long COVID” to describe a form of the viral infection from which recovery seemed impossible. (And the old nickname “long-haulers” seems so quaint now.)

What started as a pandemic that killed nearly 3 million people globally in 2020 alone would turn into a chronic disease causing a long list of symptoms — from extreme fatigue, to brain fog, tremors, nausea, headaches, rapid heartbeat, and more.

Today, 6.4% of Americans report symptoms of long COVID, and many have never recovered.

Still, we’ve come a long way, although there’s much we don’t understand about the condition. At the very least, physicians have a greater understanding that long COVID exists and can cause serious long-term symptoms.

While physicians may not have a blanket diagnostic tool that works for all patients with long COVID, they have refined existing tests for more accurate results, said Nisha Viswanathan, MD, director of the University of California Los Angeles Long COVID Program at UCLA Health.

Also, a range of new treatments, now undergoing clinical trials, have emerged that have proved effective in managing long COVID symptoms.

Catecholamine testing, for example, is now commonly used to diagnose long COVID, particularly in those who have dysautonomia, a condition caused by dysfunction of the autonomic nervous system and marked by dizziness, low blood pressure, nausea, and brain fog.

Very high levels of the neurotransmitter, for example, were shown to indicate long COVID in a January 2021 study published in the journal Clinical Medicine.

Certain biomarkers have also been shown indicative of the condition, including low serotonin levels. A study published this year in Cell found lower serotonin levels in patients with long COVID driven by low levels of circulating SARS-CoV-2, the virus that causes the condition.

Still, said Dr. Viswanathan, long COVID is a disease diagnosed by figuring out what a patient does not have — by ruling out other causes — rather than what they do. “It’s still a moving target,” she said, meaning that the disease is always changing based on the variant of acute COVID.
 

Promising Treatments Have Emerged

Dysautonomia, and especially the associated brain fog, fatigue, and dizziness, are now common conditions. As a result, physicians have gotten better at treating them. The vagus nerve is the main nerve of the parasympathetic nervous system that controls everything from digestion to mental health. A February 2022 pilot study suggested a link between vagus nerve dysfunction and some long COVID symptoms.

Vagus nerve stimulation is one form of treatment which involves using a device to stimulate the vagus nerve with electrical impulses. Dr. Viswanathan has been using the treatment in patients with fatigue, brain fog, anxiety, and depression — results, she contends, have been positive.

“This is something tangible that we can offer to patients,” she said.

Curative treatments for long COVID remain elusive, but doctors have many more tools for symptom management than before, said Ziyad Al-Aly, MD, a global expert on long COVID and chief of research and development at the Veterans Affairs St. Louis Health Care System.

For example, physicians are using beta-blockers to treat postural tachycardia syndrome (POTS), a symptom of long COVID that happens when the heart rate increases rapidly after someone stands up or lies down. Beta-blockers, such as the off-label medication ivabradine, have been used clinically to control heart rate, according to a March 2022 study published in the journal HeartRhythm Case Reports.

“It’s not a cure, but beta-blockers can help patients manage their symptoms,” said Dr. Al-Aly.

Additionally, some patients respond well to low-dose naltrexone for the treatment of extreme fatigue associated with long COVID. A January 2024 article in the journal Clinical Therapeutics found that fatigue symptoms improved in patients taking the medication.

Dr. Al-Aly said doctors treating patients with long COVID are getting better at pinpointing the phenotype or manifestation of the condition and diagnosing a treatment accordingly. Treating long COVID fatigue is not the same as treating POTS or symptoms of headache and joint pain.

It’s still all about the management of symptoms and doctors lack any US Food and Drug Administration–approved medications specifically for the condition.
 

Clinical Trials Exploring New Therapies

Still, a number of large clinical trials currently underway may change that, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

Two clinical trials headed by Dr. Putrino’s lab are looking into repurposing two HIV antivirals to see whether they affect the levels of circulating SARS-CoV-2 virus in the body that may cause long COVID. The hope is that the antivirals Truvada and maraviroc can reduce the «reactivation of latent virus» that, said Dr. Putrino, causes lingering long COVID symptoms.

Ongoing trials are looking into the promise of SARS-CoV-2 monoclonal antibodies, produced from cells made by cloning a unique white blood cell, as a treatment option. The trials are investigating whether these antibodies may similarly target viral reservoirs that are causing persistence of symptoms in some patients.

Other trials are underway through the National Institutes of Health (NIH) RECOVER initiative in which more than 17,000 patients are enrolled, the largest study of its kind, said Grace McComsey, MD.

Dr. McComsey, who leads the study at University Hospitals Health System in Cleveland, said that after following patients for up to 4 years researchers have gathered “a massive repository of information” they hope will help scientists crack the code of this very complex disease.

She and other RECOVER researchers have recently published studies on a variety of findings, reporting in February, for example, that COVID infections may trigger other autoimmune diseases such as rheumatoid arthritis and type 2 diabetes. Another recent finding showed that people with HIV are at a higher risk for complications due to acute COVID-19.
 

Lack of Urgency Holds Back Progress

Still, others like Dr. Al-Aly and Dr. Putrino felt that the initiative isn’t moving fast enough. Dr. Al-Aly said that the NIH needs to “get its act together” and do more for long COVID. In the future, he said that we need to double down on our efforts to expand funding and increase urgency to better understand the mechanism of disease, risk factors, and treatments, as well as societal and economic implications.

“We did trials for COVID-19 vaccines at warp speed, but we’re doing trials for long COVID at a snail’s pace,” he said.

Dr. Al-Aly is concerned about the chronic nature of the disease and how it affects patients down the line. His large-scale study published last month in the journal Science looked specifically at chronic fatigue syndrome triggered by the infection and its long-term impact on patients.

He’s concerned about the practical implications for people who are weighted down with symptoms for multiple years.

“Being fatigued and ill for a few months is one thing, but being at home for 5 years is a totally different ballgame.”

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

Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating. 

Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.

Researchers found that 351 patients hospitalized with severe COVID-19 had evidence of a long-term brain injury a year after contracting the SARS-CoV-2 virus. The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
 

Brain Deficits Equal to 20 Years of Brain Aging

As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.

Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.

The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.

“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
 

Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations

Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic. 

“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”

Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
 

How Do COVID-Related Brain Injuries Happen?

Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.

Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.

The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson. 

He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
 

A New Path Forward

Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.

There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.” 

“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
 

Still More to Learn

In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus. 

For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need. 

What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.

“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.

A version of this article appeared on Medscape.com.

Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating. 

Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.

Researchers found that 351 patients hospitalized with severe COVID-19 had evidence of a long-term brain injury a year after contracting the SARS-CoV-2 virus. The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
 

Brain Deficits Equal to 20 Years of Brain Aging

As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.

Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.

The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.

“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
 

Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations

Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic. 

“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”

Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
 

How Do COVID-Related Brain Injuries Happen?

Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.

Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.

The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson. 

He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
 

A New Path Forward

Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.

There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.” 

“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
 

Still More to Learn

In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus. 

For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need. 

What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.

“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.

A version of this article appeared on Medscape.com.

Brain fog is one of the most common, persistent complaints in patients with long COVID. It affects as many as 46% of patients who also deal with other cognitive concerns like memory loss and difficulty concentrating. 

Now, researchers believe they know why. A new study has found that these symptoms may be the result of a viral-borne brain injury that may cause cognitive and mental health issues that persist for years.

Researchers found that 351 patients hospitalized with severe COVID-19 had evidence of a long-term brain injury a year after contracting the SARS-CoV-2 virus. The findings were based on a series of cognitive tests, self-reported symptoms, brain scans, and biomarkers.
 

Brain Deficits Equal to 20 Years of Brain Aging

As part of the preprint study, participants took a cognition test with their scores age-matched to those who had not suffered a serious bout of COVID-19. Then a blood sample was taken to look for specific biomarkers, showing that elevated levels of certain biomarkers were consistent with a brain injury. Using brain scans, researchers also found that certain regions of the brain associated with attention were reduced in volume.

Patients who participated in the study were “less accurate and slower” in their cognition, and suffered from at least one mental health condition, such as depression, anxiety, or posttraumatic stress disorder, according to researchers.

The brain deficits found in COVID-19 patients were equivalent to 20 years of brain aging and provided proof of what doctors have feared: that this virus can damage the brain and result in ongoing mental health issues.

“We found global deficits across cognition,” said lead study author Benedict Michael, PhD, director of the Infection Neuroscience Lab at the University of Liverpool in Liverpool, England. “The cognitive and memory problems that patients complained of were associated with neuroanatomical changes to the brain.”
 

Proof That Symptoms Aren’t ‘Figment’ of Patients’ Imaginations

Cognitive deficits were common among all patients, but the researchers said they don’t yet know whether the brain damage causes permanent cognitive decline. But the research provides patients who have been overlooked by some clinicians with proof that their conditions aren’t a figment of their imaginations, said Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina School of Medicine’s COVID Recovery Clinic. 

“Even though we’re several years into this pandemic, there are still a lot of providers who don’t believe that their patients are experiencing these residual symptoms,” said Dr. Thompson, “That’s why the use of biomarkers is important, because it provides an objective indication that the brain has been compromised in some way.”

Some patients with long COVID have said that getting their doctors to believe they have a physical ailment has been a persistent problem throughout the pandemic and especially as it relates to the sometimes-vague collection of symptoms associated with brain fog. One study found that as many as 79% of study respondents reported negative interactions with their healthcare providers when they sought treatment for their long-COVID symptoms.
 

How Do COVID-Related Brain Injuries Happen?

Researchers are unsure what’s causing these brain injuries, though they have identified some clues. Previous research has suggested that such injuries might be the result of a lack of oxygen to the brain, especially in patients who were hospitalized, like those in this study, and were put on ventilators.

Brain scans have previously shown atrophy to the brain›s gray matter in COVID-19 patients, likely caused by inflammation from a heightened immune response rather than the virus itself. This inflammatory response seems to affect the central nervous system. As part of the new study, researchers found some neuroprotective effects of using steroids during hospitalization to reduce brain inflammation.

The results suggest that clinicians should overcome their skepticism and consider the possibility that their patients have suffered a brain injury and should be treated appropriately, said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University School of Medicine. “The old saying is that if it walks like a duck and talks like a duck, it’s a duck,” said Dr. Jackson. 

He contends that treatments used for patients who have brain injuries have also been shown to be effective in treating long COVID–related brain fog symptoms. These may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for the treatment of related mental health concerns.
 

A New Path Forward

Treating long-COVID brain fog like a brain injury can help patients get back to some semblance of normalcy, researchers said. “What we’re seeing in terms of brain injury biomarkers and differences in brain scans correlates to real-life problems that these patients are dealing with on a daily basis,” said Dr. Jackson. These include problems at work and in life with multitasking, remembering details, meeting deadlines, synthesizing large amounts of information, and maintaining focus on the task at hand, he said.

There’s also a fear that even with treatment, the aging of the brain caused by the virus might have long-term repercussions and that this enduring injury may cause the early onset of dementia and Alzheimer’s disease in those who were already vulnerable to it. One study, from the National Institute of Neurological Disorders and Stroke (NINDS), found that in those infected with COVID-19 who already had dementia, the virus “rapidly accelerated structural and functional brain deterioration.” 

“We already know the role that neuroinflammation plays in the brains of patients with Alzheimer’s disease,” said Dr. Thompson. “If long COVID is involved in prolonged inflammation of the brain, it goes a long way in explaining the mechanism underlying [the study’s reported] brain aging.”
 

Still More to Learn

In some ways, this study raises nearly as many questions as it does answers. While it provides concrete evidence around the damage the virus is doing to the brains of patients who contracted severe COVID-19, researchers don’t know about the impact on those who had less serious cases of the virus. 

For Ziyad Al-Aly, MD, chief of research and development at the Veterans Affairs St. Louis Health Care System, the concern is that some long-COVID patients may be suffering from cognitive deficits that are more subtle but still impacting their daily lives, and that they’re not getting the help they need. 

What’s more, said Dr. Al-Aly, it’s unclear whether the impacts of the brain damage are permanent or how to stop them from worsening. Researchers and clinicians need a better understanding of the mechanism that allows this virus to enter the brain and do structural damage. If it’s inflammation, will anti-inflammatory or antiviral medications work at preventing it? Will steroids help to offset the damage? “It’s critical we find some answers,” he said.

“SARS-CoV-2 isn’t going anywhere. It will continue to infect the population, so if this is indeed a virus that damages the brain in the long term or permanently, we need to figure out what can be done to stop it,” said Dr. Al-Aly.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

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

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

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

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

With a number of large-scale clinical trials underway and researchers on the hunt for new therapies, long COVID scientists are hopeful that this is the year patients — and doctors who care for them — will finally see improvements in treating their symptoms.

Here are five bold predictions — all based on encouraging research — that could happen in 2024. At the very least, they are promising signs of progress against a debilitating and frustrating disease.

#1: We’ll gain a better understanding of each long COVID phenotype

This past year, a wide breadth of research began showing that long COVID can be defined by a number of different disease phenotypes that present a range of symptoms.

Researchers identified four clinical phenotypes: Chronic fatigue-like syndrome, headache, and memory loss; respiratory syndrome, which includes cough and difficulty breathing; chronic pain; and neurosensorial syndrome, which causes an altered sense of taste and smell.

Identifying specific diagnostic criteria for each phenotype would lead to better health outcomes for patients instead of treating them as if it were a “one-size-fits-all disease,” said Nisha Viswanathan, MD, director of the long COVID program at UCLA Health, Los Angeles, California.

Ultimately, she hopes that this year her patients will receive treatments based on the type of long COVID they’re personally experiencing, and the symptoms they have, leading to improved health outcomes and more rapid relief.

“Many new medications are focused on different pathways of long COVID, and the challenge becomes which drug is the right drug for each treatment,” said Dr. Viswanathan.

#2: Monoclonal antibodies may change the game

We’re starting to have a better understanding that what’s been called “viral persistence” as a main cause of long COVID may potentially be treated with monoclonal antibodies. These are antibodies produced by cloning unique white blood cells to target the circulating spike proteins in the blood that hang out in viral reservoirs and cause the immune system to react as if it’s still fighting acute COVID-19.

Smaller-scale studies have already shown promising results. A January 2024 study published in The American Journal of Emergency Medicine followed three patients who completely recovered from long COVID after taking monoclonal antibodies. “Remission occurred despite dissimilar past histories, sex, age, and illness duration,” wrote the study authors.

Larger clinical trials are underway at the University of California, San Francisco, California, to test targeted monoclonal antibodies. If the results of the larger study show that monoclonal antibodies are beneficial, then it could be a game changer for a large swath of patients around the world, said David F. Putrino, PhD, who runs the long COVID clinic at Mount Sinai Health System in New York City.

“The idea is that the downstream damage caused by viral persistence will resolve itself once you wipe out the virus,” said Dr. Putrino.

#3: Paxlovid could prove effective for long COVID

The US Food and Drug Administration granted approval for Paxlovid last May for the treatment of mild to moderate COVID-19 in adults at a high risk for severe disease. The medication is made up of two drugs packaged together. The first, nirmatrelvir, works by blocking a key enzyme required for virus replication. The second, ritonavir, is an antiviral that’s been used in patients with HIV and helps boost levels of antivirals in the body.

In a large-scale trial headed up by Dr. Putrino and his team, the oral antiviral is being studied for use in the post-viral stage in patients who test negative for acute COVID-19 but have persisting symptoms of long COVID.

Similar to monoclonal antibodies, the idea is to quell viral persistence. If patients have long COVID because they can’t clear SAR-CoV-2 from their bodies, Paxlovid could help. But unlike monoclonal antibodies that quash the virus, Paxlovid stops the virus from replicating. It’s a different mechanism with the same end goal.

It’s been a controversial treatment because it’s life-changing for some patients and ineffective for others. In addition, it can cause a range of side effects such as diarrhea, nausea, vomiting, and an impaired sense of taste. The goal of the trial is to see which patients with long COVID are most likely to benefit from the treatment.

#4: Anti-inflammatories like metformin could prove useful

Many of the inflammatory markers persistent in patients with long COVID were similarly present in patients with autoimmune diseases like rheumatoid arthritis, according to a July 2023 study published in JAMA.

The hope is that anti-inflammatory medications may be used to reduce inflammation causing long COVID symptoms. But drugs used to treat rheumatoid arthritis like abatacept and infliximabcan also have serious side effects, including increased risk for infection, flu-like symptoms, and burning of the skin.

“Powerful anti-inflammatories can change a number of pathways in the immune system,” said Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, Ohio. Anti-inflammatories hold promise but, Dr. McComsey said, “some are more toxic with many side effects, so even if they work, there’s still a question about who should take them.”

Still, other anti-inflammatories that could work don’t have as many side effects. For example, a study published in The Lancet Infectious Diseases found that the diabetes drug metformin reduced a patient’s risk for long COVID up to 40% when the drug was taken during the acute stage.

Metformin, compared to other anti-inflammatories (also known as immune modulators), is an inexpensive and widely available drug with relatively few side effects compared with other medications.

#5: Serotonin levels — and selective serotonin reuptake inhibitors (SSRIs) — may be keys to unlocking long COVID

One of the most groundbreaking studies of the year came last November. A study published in the journal Cell found lower circulating serotonin levels in patents with long COVID than in those who did not have the condition. The study also found that the SSRI fluoxetine improved cognitive function in rat models infected with the virus.

Researchers found that the reduction in serotonin levels was partially caused by the body’s inability to absorb tryptophan, an amino acid that’s a precursor to serotonin. Overactivated blood platelets may also have played a role.

Michael Peluso, MD, an assistant research professor of infectious medicine at the UCSF School of Medicine, San Francisco, California, hopes to take the finding a step further, investigating whether increased serotonin levels in patients with long COVID will lead to improvements in symptoms.

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

If patients show an improvement in symptoms, then the next step is looking into whether SSRIs boost serotonin levels in patients and, as a result, reduce their symptoms.

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

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

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

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

Kate Whitley was petrified of COVID-19 from the beginning of the pandemic because she has Hashimoto disease, an autoimmune disorder that she knew put her at high risk for complications.

She was right to be worried. Two months after contracting the infection in September 2022, the 42-year-old Nashville resident was diagnosed with long COVID. For Ms. Whitley, the resulting brain fog has been the most challenging factor. She is the owner of a successful paper goods store, and she can’t remember basic aspects of her job. She can’t tolerate loud noises and gets so distracted that she has trouble remembering what she was doing.

Ms. Whitley doesn’t like the term “brain fog” because it doesn’t begin to describe the dramatic disruption to her life over the past 7 months.

“I just can’t think anymore,” she said. “It makes you realize that you’re nothing without your brain. Sometimes I feel like a shell of my former self.”

Brain fog is among the most common symptoms of long COVID, and also one of the most poorly understood. A reported 46% of those diagnosed with long COVID complain of brain fog or a loss of memory. Many clinicians agree that the term is vague and often doesn’t truly represent the condition. That, in turn, makes it harder for doctors to diagnose and treat it. There are no standard tests for it, nor are there guidelines for symptom management or treatment.

“There’s a lot of imprecision in the term because it might mean different things to different patients,” said James C. Jackson, PsyD, a neuropsychiatrist at Vanderbilt University, Nashville, Tenn., and author of a new book, “Clearing the Fog: From Surviving to Thriving With Long COVID – A Practical Guide.”

Dr. Jackson, who began treating Ms. Whitley in February 2023, said that it makes more sense to call brain fog a brain impairment or an acquired brain injury (ABI) because it doesn’t occur gradually. COVID damages the brain and causes injury. For those with long COVID who were previously in the intensive care unit and may have undergone ventilation, hypoxic brain injury may result from the lack of oxygen to the brain.

Even among those with milder cases of acute COVID, there’s some evidence that persistent neuroinflammation in the brain caused by an activated immune system may also cause damage.

In both cases, the results can be debilitating. Ms. Whitley also has dysautonomia – a disorder of the autonomic nervous system that can cause dizziness, sweating, and headaches along with fatigue and heart palpitations.

She said that she’s so forgetful that when she sees people socially, she’s nervous of what she’ll say. “I feel like I’m constantly sticking my foot in my mouth because I can’t remember details of other people’s lives,” she said.

Although brain disorders such as Alzheimer’s disease and other forms of dementia are marked by a slow decline, ABI occurs more suddenly and may include a loss of executive function and attention.

“With a brain injury, you’re doing fine, and then some event happens (in this case COVID), and immediately after that, your cognitive function is different,” said Dr. Jackson.

Additionally, ABI is an actual diagnosis, whereas brain fog is not.

“With a brain injury, there’s a treatment pathway for cognitive rehabilitation,” said Dr. Jackson.

Treatments may include speech, cognitive, and occupational therapy as well as meeting with a neuropsychiatrist for treatment of the mental and behavioral disorders that may result. Dr. Jackson said that while many patients aren’t functioning cognitively or physically at 100%, they can make enough strides that they don’t have to give up things such as driving and, in some cases, their jobs.

Other experts agree that long COVID may damage the brain. An April 2022 study published in the journal Nature found strong evidence that SARS-CoV-2 infection may cause brain-related abnormalities, for example, a reduction in gray matter in certain parts of the brain, including the prefrontal cortex, hypothalamus, and amygdala.

Additionally, white matter, which is found deeper in the brain and is responsible for the exchange of information between different parts of the brain, may also be at risk of damage as a result of the virus, according to a November 2022 study published in the journal SN Comprehensive Clinical Medicine.

Calling it a “fog” makes it easier for clinicians and the general public to dismiss its severity, said Tyler Reed Bell, PhD, a researcher who specializes in viruses that cause brain injury. He is a fellow in the department of psychiatry at the University of California, San Diego. Brain fog can make driving and returning to work especially dangerous. Because of difficulty focusing, patients are much more likely to make mistakes that cause accidents.

“The COVID virus is very invasive to the brain,” Dr. Bell said.

Others contend this may be a rush to judgment. Karla L. Thompson, PhD, lead neuropsychologist at the University of North Carolina at Chapel Hill’s COVID Recovery Clinic, agrees that in more serious cases of COVID that cause a lack of oxygen to the brain, it’s reasonable to call it a brain injury. But brain fog can also be associated with other long COVID symptoms, not just damage to the brain.

Chronic fatigue and poor sleep are both commonly reported symptoms of long COVID that negatively affect brain function, she said. Sleep disturbances, cardiac problems, dysautonomia, and emotional distress could also affect the way the brain functions post COVID. Finding the right treatment requires identifying all the factors contributing to cognitive impairment.

Part of the problem in treating long COVID brain fog is that diagnostic technology is not sensitive enough to detect inflammation that could be causing damage.

Grace McComsey, MD, who leads the long COVID RECOVER study at University Hospitals Health System in Cleveland, said her team is working on identifying biomarkers that could detect brain inflammation in a way similar to the manner researchers have identified biomarkers to help diagnose chronic fatigue syndrome. Additionally, a new study published last month in JAMA for the first time clearly defined 12 symptoms of long COVID, and brain fog was listed among them. All of this contributes to the development of clear diagnostic criteria.

“It will make a big difference once we have some consistency among clinicians in diagnosing the condition,” said Dr. McComsey.

Ms. Whitley is thankful for the treatment that she’s received thus far. She’s seeing a cognitive rehabilitation therapist, who assesses her memory, cognition, and attention span and gives her tools to break up simple tasks, such as driving, so that they don’t feel overwhelming. She’s back behind the wheel and back to work.

But perhaps most importantly, Ms. Whitley joined a support group, led by Dr. Jackson, that includes other people experiencing the same symptoms she is. When she was at her darkest, they understood.

“Talking to other survivors has been the only solace in all this,” Ms. Whitley said. “Together, we grieve all that’s been lost.”

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

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

In the mid-1990s, when Somnath Saha was a medical resident at the University of California, San Francisco, School of Medicine, he came across a cluster of studies showing that Black people with cardiovascular disease were treated less aggressively, compared with White people. The findings were “appalling” to the young physician who describes himself as a “Brown kid from suburban St. Louis, Missouri.”

Dr. Saha had experienced racism growing up, but was surprised to see such clear signs of inequity within the field of medicine. “There was an injustice happening in my own backyard,” he said.

Indeed, bias towards Black patients can be challenging because many doctors either don’t realize their biases or won’t admit to them. Dr. Saha, now a professor of medicine at Johns Hopkins University, likens implicit bias – unconscious judgments that can affect behavior – to “an invisible force.”

While numerous studies have found evidence of racial discrimination in medicine through patient reports, less is known about how implicit bias shows up in medical records, and how stigmatizing language in patient notes can affect the care that Black patients receive.

That’s part of the reason why, about 7 years ago, Dr. Saha began poring through medical records. For him, they offered a window into doctors’ feelings about their patients.

As part of his latest research, Dr. Saha’s team examined the records of nearly 19,000 patients, paying particular attention to negative descriptions that may influence a clinician’s decision-making. The data, which were recently presented at the 2023 American Association for the Advancement of Science annual meeting, aren’t yet published, but it suggests what researchers have long speculated: Doctors are more likely to use negative language when describing a Black patient than they are in describing a White patient. The notes provide, at times, a surprisingly candid view of how patients are perceived by doctors, and how their race may affect treatment.

The study adds to a concerning body of literature that explores how racial bias manifests in health care. Researchers like Dr. Saha are interested in how such prejudice leaves a paper trail, which can then reinforce negative stereotypes. Because medical notes get passed between physicians, Dr. Saha’s research suggests they can affect the health of Black patients down the line.

“The medical record is like a rap sheet, it stays with you,” Dr. Saha said, adding that “these things that we say about patients get eternalized.”

Research has long shown that Black patients experience worse health outcomes, compared with White patients, in part because of biased medical care. Black women, for example, are three times more likely to die from pregnancy-related complications, compared with White women. And Black patients often report feeling like physicians don’t listen to their needs or don’t believe their concerns.

Studies appear to back that up. Last year, researchers at the University of Washington found that non-Hispanic White children who went to the emergency room for migraines were more likely to receive pain medications, compared with children of color – even though the two groups reported similar pain scores. Other studies echo similar results for adults as well.

While Michael Sun, a resident physician at the University of Chicago, knew about such health disparities, by his own admission, he was naive about the biases in medical records. At that time, Dr. Sun had “no experience in the medical record, in documentation, or in physician language and culture,” he said.

But in Dr. Sun’s first year of medical school, his professor shared the story of a longtime patient, whom she had referred to an outside specialist. In his recollection, the professor regarded her patient in kind terms, having worked with her for some time to treat a chronic illness. But when she got the specialist’s notes back, she was confused by the description of her patient: Terms like “really difficult,” “noncompliant,” and “uninterested in their health.” This was not the patient she remembered.

“This, as a first-year medical student, really shocked me because I had taken at face value that any words used in notes were true, were valid, or rightfully used,” said Dr. Sun. “I realized all the ways that bias, untold stories, and unknown context may change the way that we view our patients.”

Like Dr. Saha, Dr. Sun became interested in how bias influenced the relationship between doctor and patient, and how these interactions were memorialized in the medical record. In a study published last year, he and his colleagues looked at more than 40,000 medical notes from 18,459 patients. Researchers first manually combed through the notes, then used this information to teach a machine learning algorithm to interpret the connotations of words. Compared with White patients, Black patients were about 2.5 times more likely to be described negatively, with terms like “challenging,” “angry,” and “noncompliant.”

Dr. Saha has used similar methodology – and found similar results – in his own research. For the study presented at the AAAS meeting, his team first read through more than 100,000 medical notes to identify language their team considered to be disparaging – which they chose based on a list of words and phrases from prior research. They then used machine learning to find those terms in medical notes, taking care to ensure context was considered. For example, if the word “aggressive” was used to describe a treatment plan, it was excluded from their analysis. But if “aggressive” was used to describe the patient, it was included.

Dr. Saha pointed to three categories of stigmatizing language that were the most pronounced: expressing doubt or disbelief in what the patient said, such as reporting they “claimed” to experience pain; insinuating that the patient was confrontational, using words like “belligerent” or combative;” and suggesting a patient was not cooperating with a doctor’s orders by saying they “refused” medical advice.

“We’ve known for some time that in health care we sometimes use language that can be confusing or even insulting,” Matthew Wynia, director of the Center for Bioethics and Humanities at the University of Colorado at Denver, Aurora, wrote in an email to Undark. But he noted that research such as Dr. Saha’s has drawn attention to a previously overlooked issue. Describing a patient as “noncompliant” with medications, he said, “makes it sound like the patient is intentionally refusing to follow advice when, in fact, there are many reasons why people might not be able to follow our advice and intentional refusal isn’t even a very common one.”

Dr. Saha noted that, if a patient isn’t taking their medication, it’s important that doctors note that, so that the next physician doesn’t overprescribe them. But the concern, he said, is whether doctors are using these terms appropriately and for the right reasons because of the implications they have for patients.

If a doctor portrays their patient negatively, Dr. Saha said, it can “trigger the next clinician to read them and formulate a potentially negative opinion about that patient” before they’ve even had a chance to interact.

Still, stigmatizing language is only one small piece of the puzzle. What also matters, Dr. Saha said, is how those words can have an impact on care. In prior work, Dr. Saha has shown how implicit and, in some cases, explicit bias, affects a patient’s treatment recommendations.

In a 2018 study, Dr. Saha, along with his wife, Mary Catherine Beach – also a professor at Johns Hopkins University – combed through reports of patients with sickle cell anemia. Their team focused on that particular population since sickle cell patients are some of the most stigmatized in the health care system: Most patients are Black and many require regular doses of opioids for pain management.

In the notes, they found numerous examples of details that were irrelevant to patients’ health concerns: phrases like “girlfriend requests bus token,” “cursing at nurse,” “girlfriend on bed with shoes on,” and “narcotic dependent.”

Dr. Saha and Dr. Beach wanted to see how these remarks might influence a physician’s treatment recommendations, so they used vignettes they had found in the medical records of sickle cell patients. They showed either a vignette which had described patients negatively, or one that was edited with neutral language. Then they asked medical students and residents about the dose of pain medication they would hypothetically recommend. Dr. Beach said that the purpose was to see how what she called “dog whistles about social class or race or something that would make the person seem less educated” would impact treatment recommendations.

The study found that medical notes with stigmatizing language were associated with “less aggressive management of the patient’s pain.” Doctors who read the stigmatizing language chart notes prescribed less pain medication to patients even in cases when they commented that their pain was a 10 out of 10.

“The fact that we were able to show that this bias transmits to the next doctor has been the thing that I think motivates doctors to take it seriously,” said Dr. Beach.

Pain management has become a focal point for researchers because many of the most glaring racial tropes about patient care have revolved around pain. In 2016, a study conducted at the University of Virginia found that half of the 418 medical students and residents surveyed endorsed false beliefs about Black patients. For example, that “Blacks’ nerve endings are less sensitive than whites” and “Blacks’ skin is thicker than whites.” What’s more, those who endorsed these false beliefs also rated Black patients’ pain as lower than White patients’.

Antoinette M. Schoenthaler, a professor of population health and medicine at New York University and associate director of research at the school’s Institute for Excellence in Health Equity, said that disparities in pain management are pervasive and widespread across the medical profession. They seep into treatments for sickle cell anemia, but also prenatal care. As a result, she said, Black patients across the board are often fearful of attending appointments.

“Patients of color go into an appointment with feelings of heightened anxiety because they’re expecting mistreatment,” said Dr. Schoenthaler. “We’ve seen minoritized patients have higher blood pressure in the context of a clinical visit because of these expectations of anxiety and fear, and disappointment.”

Disparities in health care between Black and White patients is a complex issue – one which can’t be solved by addressing medical records alone. But, for researchers like Dr. Saha, Dr. Beach, and Dr. Sun, they can offer a road map that outlines where differences in care begin. The words a clinician uses sets the path for how a patient may be treated in the future.

One way to combat implicit bias, Dr. Saha suggested, is to use an algorithm that identifies stigmatizing language to “give hospital departments or clinicians report cards on how much of this language that they’re using.” By benchmarking averages against one another, clinicians could know if they’re using stigmatizing language at an above average rate. This is something he is considering for future research.

When clinicians are made aware of their biases – when the unconscious becomes conscious – Dr. Saha told Undark that he’s optimistic they’ll work to change them: “We’re using language that we’ve used forever without realizing the potential impact that it has on patient care.”

This article originated on Undark. A version of this article appeared on Medscape.com.

It’s not often that a high school brawl with gang members sets you down a path to becoming a Harvard-trained doctor. But that’s exactly how Alister Martin’s life unfolded.

Alister Martin, MD, had initially planned to follow in his stepfather’s footsteps, managing the drug store in Neptune, N.J., township where he was raised. But a fight changed his prospects. 

In retrospect, he should have seen the whole thing coming. That night at the party, his best friend was attacked by a gang member from a nearby high school. Martin was not in a gang but he jumped into the fray to defend his friend. 

“I wanted to save the day, but that’s not what happened,” he says. “There were just too many of them.”

When his mother rushed to the hospital, he was so bruised and bloody that she couldn’t recognize him at first. Ever since he was a baby, she had done her best to shield him from the neighborhood where gang violence was a regular disruption. But it hadn’t worked. 

“My high school had a zero-tolerance policy for gang violence,” Martin says, “so even though I wasn’t in a gang, I was kicked out.”

Now expelled from high school, his mother wanted him out of town, fearing gang retaliation, or that Martin might seek vengeance on the boy who had brutally beaten him. So, the biology teacher and single mom who worked numerous jobs to keep them afloat, came up with a plan to get him far away from any temptations.

Martin had loved tennis since middle school, when his 8th-grade math teacher, Billie Weise, also a tennis pro, got him a job as a court sweeper at an upscale tennis club nearby. He knew nothing then about tennis but would come to fall in love with the sport. To get her son out of town, Martin’s mother took out loans for $30,000 and sent him to a Florida tennis training camp.

After 6 months of training, Martin, who earned a GED degree while attending the camp, was offered a scholarship to play tennis at Rutgers University in New Brunswick, N.J. The transition to college was tough, however. He was nervous and felt out of place. “I could have died that first day. It became so obvious how poorly my high school education had prepared me for this.”

But the unease he felt was also motivating in a way. Worried about failure, “he locked himself in a room with another student and they studied day and night,” recalls Kamal Khan, director of the office for diversity and academic success at Rutgers. “I’ve never seen anything like it.”

And Martin displayed other attributes that would draw others to him – and later prove important in his career as a doctor. His ability to display empathy and interact with students and teachers separated him from his peers, Mr. Khan says. “There’re a lot of really smart students out there,” he says, “but not many who understand people like Martin.”

After graduating, he decided to pursue his dream of becoming a doctor. He’d wanted to be a doctor since he was 10 years old after his mom was diagnosed with metastatic breast cancer. He remembers overhearing a conversation she was having with a family friend about where he would go if she died. 

“That’s when I knew it was serious,” he says.

Doctors saved her life, and it’s something he’ll never forget. But it wasn’t until his time at Rutgers that he finally had the confidence to think he could succeed in medical school.

Martin went on to attend Harvard Medical School and Harvard Kennedy School of Government as well as serving as chief resident at Brigham and Women’s Hospital. He was also a fellow at the White House in the Office of the Vice President and today, he’s an assistant professor at Harvard Medical School in Boston..

He is most at home in the emergency room at Massachusetts General Hospital, where he works as an emergency medical specialist. For him, the ER is the first line of defense for meeting the community’s health needs. Growing up in Neptune, the ER “was where poor folks got their care,” he says. His mom worked two jobs and when she got off work at 8 p.m. there was no pediatrician open. “When I was sick as a kid we always went to the emergency room,” he says.

While at Harvard, he also pursued a degree from the Kennedy School of Government, because of the huge role he feels that politics play in our health care system and especially in bringing care to impoverished communities. And since then he’s taken numerous steps to bridge the gap.

Addiction, for example, became an important issue for Martin, ever since a patient he encountered in his first week as an internist. She was a mom of two who had recently gotten surgery because she broke her ankle falling down the stairs at her child’s daycare, he says. Prescribed oxycodone, she feared she was becoming addicted and needed help. But at the time, there was nothing the ER could do. 

“I remember that look in her eyes when we had to turn her away,” he says. 

Martin has worked to change protocol at his hospital and others throughout the nation so they can be better set up to treat opioid addiction. He’s the founder of GetWaivered, an organization that trains doctors throughout the country to use evidence-based medicine to manage opioid addiction. In the U.S. doctors need what’s called a DEA X waiver to be able to prescribe buprenorphine to opioid-addicted patients. That means that currently only about 1% of all emergency room doctors nationwide have the waiver and without it, it’s impossible to help patients when they need it the most.

Shuhan He, MD, an internist with Martin at Massachusetts General Hospital who also works on the GetWaivered program, says Martin has a particular trait that helps him be successful. 

“He’s a doer and when he sees a problem, he’s gonna try and fix it.”

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

It’s not often that a high school brawl with gang members sets you down a path to becoming a Harvard-trained doctor. But that’s exactly how Alister Martin’s life unfolded.

Alister Martin, MD, had initially planned to follow in his stepfather’s footsteps, managing the drug store in Neptune, N.J., township where he was raised. But a fight changed his prospects. 

In retrospect, he should have seen the whole thing coming. That night at the party, his best friend was attacked by a gang member from a nearby high school. Martin was not in a gang but he jumped into the fray to defend his friend. 

“I wanted to save the day, but that’s not what happened,” he says. “There were just too many of them.”

When his mother rushed to the hospital, he was so bruised and bloody that she couldn’t recognize him at first. Ever since he was a baby, she had done her best to shield him from the neighborhood where gang violence was a regular disruption. But it hadn’t worked. 

“My high school had a zero-tolerance policy for gang violence,” Martin says, “so even though I wasn’t in a gang, I was kicked out.”

Now expelled from high school, his mother wanted him out of town, fearing gang retaliation, or that Martin might seek vengeance on the boy who had brutally beaten him. So, the biology teacher and single mom who worked numerous jobs to keep them afloat, came up with a plan to get him far away from any temptations.

Martin had loved tennis since middle school, when his 8th-grade math teacher, Billie Weise, also a tennis pro, got him a job as a court sweeper at an upscale tennis club nearby. He knew nothing then about tennis but would come to fall in love with the sport. To get her son out of town, Martin’s mother took out loans for $30,000 and sent him to a Florida tennis training camp.

After 6 months of training, Martin, who earned a GED degree while attending the camp, was offered a scholarship to play tennis at Rutgers University in New Brunswick, N.J. The transition to college was tough, however. He was nervous and felt out of place. “I could have died that first day. It became so obvious how poorly my high school education had prepared me for this.”

But the unease he felt was also motivating in a way. Worried about failure, “he locked himself in a room with another student and they studied day and night,” recalls Kamal Khan, director of the office for diversity and academic success at Rutgers. “I’ve never seen anything like it.”

And Martin displayed other attributes that would draw others to him – and later prove important in his career as a doctor. His ability to display empathy and interact with students and teachers separated him from his peers, Mr. Khan says. “There’re a lot of really smart students out there,” he says, “but not many who understand people like Martin.”

After graduating, he decided to pursue his dream of becoming a doctor. He’d wanted to be a doctor since he was 10 years old after his mom was diagnosed with metastatic breast cancer. He remembers overhearing a conversation she was having with a family friend about where he would go if she died. 

“That’s when I knew it was serious,” he says.

Doctors saved her life, and it’s something he’ll never forget. But it wasn’t until his time at Rutgers that he finally had the confidence to think he could succeed in medical school.

Martin went on to attend Harvard Medical School and Harvard Kennedy School of Government as well as serving as chief resident at Brigham and Women’s Hospital. He was also a fellow at the White House in the Office of the Vice President and today, he’s an assistant professor at Harvard Medical School in Boston..

He is most at home in the emergency room at Massachusetts General Hospital, where he works as an emergency medical specialist. For him, the ER is the first line of defense for meeting the community’s health needs. Growing up in Neptune, the ER “was where poor folks got their care,” he says. His mom worked two jobs and when she got off work at 8 p.m. there was no pediatrician open. “When I was sick as a kid we always went to the emergency room,” he says.

While at Harvard, he also pursued a degree from the Kennedy School of Government, because of the huge role he feels that politics play in our health care system and especially in bringing care to impoverished communities. And since then he’s taken numerous steps to bridge the gap.

Addiction, for example, became an important issue for Martin, ever since a patient he encountered in his first week as an internist. She was a mom of two who had recently gotten surgery because she broke her ankle falling down the stairs at her child’s daycare, he says. Prescribed oxycodone, she feared she was becoming addicted and needed help. But at the time, there was nothing the ER could do. 

“I remember that look in her eyes when we had to turn her away,” he says. 

Martin has worked to change protocol at his hospital and others throughout the nation so they can be better set up to treat opioid addiction. He’s the founder of GetWaivered, an organization that trains doctors throughout the country to use evidence-based medicine to manage opioid addiction. In the U.S. doctors need what’s called a DEA X waiver to be able to prescribe buprenorphine to opioid-addicted patients. That means that currently only about 1% of all emergency room doctors nationwide have the waiver and without it, it’s impossible to help patients when they need it the most.

Shuhan He, MD, an internist with Martin at Massachusetts General Hospital who also works on the GetWaivered program, says Martin has a particular trait that helps him be successful. 

“He’s a doer and when he sees a problem, he’s gonna try and fix it.”

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

It’s not often that a high school brawl with gang members sets you down a path to becoming a Harvard-trained doctor. But that’s exactly how Alister Martin’s life unfolded.

Alister Martin, MD, had initially planned to follow in his stepfather’s footsteps, managing the drug store in Neptune, N.J., township where he was raised. But a fight changed his prospects. 

In retrospect, he should have seen the whole thing coming. That night at the party, his best friend was attacked by a gang member from a nearby high school. Martin was not in a gang but he jumped into the fray to defend his friend. 

“I wanted to save the day, but that’s not what happened,” he says. “There were just too many of them.”

When his mother rushed to the hospital, he was so bruised and bloody that she couldn’t recognize him at first. Ever since he was a baby, she had done her best to shield him from the neighborhood where gang violence was a regular disruption. But it hadn’t worked. 

“My high school had a zero-tolerance policy for gang violence,” Martin says, “so even though I wasn’t in a gang, I was kicked out.”

Now expelled from high school, his mother wanted him out of town, fearing gang retaliation, or that Martin might seek vengeance on the boy who had brutally beaten him. So, the biology teacher and single mom who worked numerous jobs to keep them afloat, came up with a plan to get him far away from any temptations.

Martin had loved tennis since middle school, when his 8th-grade math teacher, Billie Weise, also a tennis pro, got him a job as a court sweeper at an upscale tennis club nearby. He knew nothing then about tennis but would come to fall in love with the sport. To get her son out of town, Martin’s mother took out loans for $30,000 and sent him to a Florida tennis training camp.

After 6 months of training, Martin, who earned a GED degree while attending the camp, was offered a scholarship to play tennis at Rutgers University in New Brunswick, N.J. The transition to college was tough, however. He was nervous and felt out of place. “I could have died that first day. It became so obvious how poorly my high school education had prepared me for this.”

But the unease he felt was also motivating in a way. Worried about failure, “he locked himself in a room with another student and they studied day and night,” recalls Kamal Khan, director of the office for diversity and academic success at Rutgers. “I’ve never seen anything like it.”

And Martin displayed other attributes that would draw others to him – and later prove important in his career as a doctor. His ability to display empathy and interact with students and teachers separated him from his peers, Mr. Khan says. “There’re a lot of really smart students out there,” he says, “but not many who understand people like Martin.”

After graduating, he decided to pursue his dream of becoming a doctor. He’d wanted to be a doctor since he was 10 years old after his mom was diagnosed with metastatic breast cancer. He remembers overhearing a conversation she was having with a family friend about where he would go if she died. 

“That’s when I knew it was serious,” he says.

Doctors saved her life, and it’s something he’ll never forget. But it wasn’t until his time at Rutgers that he finally had the confidence to think he could succeed in medical school.

Martin went on to attend Harvard Medical School and Harvard Kennedy School of Government as well as serving as chief resident at Brigham and Women’s Hospital. He was also a fellow at the White House in the Office of the Vice President and today, he’s an assistant professor at Harvard Medical School in Boston..

He is most at home in the emergency room at Massachusetts General Hospital, where he works as an emergency medical specialist. For him, the ER is the first line of defense for meeting the community’s health needs. Growing up in Neptune, the ER “was where poor folks got their care,” he says. His mom worked two jobs and when she got off work at 8 p.m. there was no pediatrician open. “When I was sick as a kid we always went to the emergency room,” he says.

While at Harvard, he also pursued a degree from the Kennedy School of Government, because of the huge role he feels that politics play in our health care system and especially in bringing care to impoverished communities. And since then he’s taken numerous steps to bridge the gap.

Addiction, for example, became an important issue for Martin, ever since a patient he encountered in his first week as an internist. She was a mom of two who had recently gotten surgery because she broke her ankle falling down the stairs at her child’s daycare, he says. Prescribed oxycodone, she feared she was becoming addicted and needed help. But at the time, there was nothing the ER could do. 

“I remember that look in her eyes when we had to turn her away,” he says. 

Martin has worked to change protocol at his hospital and others throughout the nation so they can be better set up to treat opioid addiction. He’s the founder of GetWaivered, an organization that trains doctors throughout the country to use evidence-based medicine to manage opioid addiction. In the U.S. doctors need what’s called a DEA X waiver to be able to prescribe buprenorphine to opioid-addicted patients. That means that currently only about 1% of all emergency room doctors nationwide have the waiver and without it, it’s impossible to help patients when they need it the most.

Shuhan He, MD, an internist with Martin at Massachusetts General Hospital who also works on the GetWaivered program, says Martin has a particular trait that helps him be successful. 

“He’s a doer and when he sees a problem, he’s gonna try and fix it.”

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

Could taking vitamin C help reduce the chances of developing gout? A new study sheds light on this possibility.

Gout is a form of inflammatory arthritis that has been on the rise in the United States in recent decades. Considered a lifestyle disease, some research has shown that instances of the condition have more than doubled in recent years as rates of obesity have skyrocketed. It’s caused by uric acid in the blood that builds up and crystallizes in the joints. Flare-ups are so intense that the joints can turn a cherry red and vibrate with intense – and sometimes seemingly intolerable – pain.

Dmytro Panchenko/iStockphoto

While there are effective treatments, many people fail to take their medications when they’re not in pain, and if the condition goes unchecked, it can get much worse and cause permanent damage to the joints.

“Gout can cause flare-ups that vary in frequency and severity; but sometimes when people aren’t experiencing them, they’re less likely to stay on top of their medications,” said Stephen Juraschek, MD, an assistant professor of medicine at Harvard Medical School, Boston.

That’s why lifestyle interventions are seen as particularly relevant to a disease like gout. Vitamin C, for example, has few side effects, and for those with higher levels of uric acid in the blood, it could reduce the likelihood of getting the condition. A recent study published in The American Journal of Clinical Nutrition found that people who were given 500 mg of vitamin C versus a placebo had a 12% reduced risk of getting gout. The study of over 14,000 male doctors showed that men who weren’t overweight had the most significant reduction in the risk of getting the condition. (Excess weight has been shown to increase the risk of gout.)

As part of the study, participants responded to a questionnaire that asked whether they had ever been diagnosed with gout. Other studies have shown that vitamin C reduced the levels of urate in people without gout and broke down uric crystals in the blood, but this study took it a step further to show that the supplement actually reduced the risk of getting the condition.

“In addition to lowering levels of uric acid in the body, it’s thought that vitamin C may also minimize the inflammatory response to urate crystals,” said Dr. Juraschek. That’s because when flare-ups develop in joints throughout the body, much of the painful irritation is caused by the immune system’s response as it fights to break down the crystals.

Dr. Juraschek said this likely wouldn’t change recommendations for patients with serious gout, but it could still have an impact.

“For individuals who were told that they have gout but have had fewer flare-ups, they might be more open to taking vitamin C,” he said.

Will Settle, 42, of Hilton Head, S.C., was not involved in the study, but he said he would be inclined to try most any safe preventive method. Gout runs in his family. His father and grandfather had it, and now, so does he. His flare-ups have slowed in recent years, which he said has a lot to do with his diet and lifestyle. He stopped eating seafood, started drinking more water, and stopped drinking as much alcohol – all of which he thinks has had a huge impact on the severity of his condition. (Both seafood and beer contain high levels of purines, which have been shown to increase the buildup of uric acid in the blood.) Mr. Settle said that other simple lifestyle changes like vitamin C would be an easy addition to his routine with few downsides. Plus, he hates having to take colchicine, a medication that’s meant to relieve pain but causes him intense diarrhea when he takes it.

“Anything to reduce my flare-ups without having to take colchicine,” he said.

But the jury is still out as to whether vitamin C will have any real benefits. Study coauthor Robert H. Shmerling, MD, is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center, New York. He said the study shows that the effect of vitamin C in those undiagnosed with gout was rather modest. Also, vitamin C did not show a reduction in gout flare-ups in those who were already diagnosed with the condition. Not to mention that the study lacked diversity, as the people in it were all male and mostly white. Still, there’s little downside risk to taking vitamin C, and it might end up being worthwhile.

“Maybe it will turn out to be an effective treatment in those who are at high risk, but we’re not there yet,” he said.

Robert Terkeltaub, MD, chief of rheumatology at the Veterans Administration Medical Center in San Diego and a professor of medicine at the University of California, San Diego, said there’s an unmet need when it comes to tools for gout prevention.

“The disease impacts some 10 million Americans, and we need to better identify these individuals so we can intervene earlier,” he said.

While vitamin C had a small but significant association with fewer new cases of gout, it did not lower it in those who already had the disease, said Dr. Terkeltaub. What’s more, researchers didn’t measure the levels of uric acid in the blood, which would have painted a more accurate picture of whether vitamin C actually reduced it in the body.

“There remains no clarity on the potential role of vitamin C in either prevention or treatment of gout. That said, future research would be of interest,” he said.

Still, gout patients like Mr. Settle aren’t ruling it out. Anything to avoid the pain that, at times, makes it difficult for him to get out of bed. He’s seen the benefit that simple lifestyle changes can make, and he’s willing to try just about anything to live a normal, arthritis-free life.

“I’m always looking for simple ways to keep my flare-ups at bay,” he said.

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

Could taking vitamin C help reduce the chances of developing gout? A new study sheds light on this possibility.

Gout is a form of inflammatory arthritis that has been on the rise in the United States in recent decades. Considered a lifestyle disease, some research has shown that instances of the condition have more than doubled in recent years as rates of obesity have skyrocketed. It’s caused by uric acid in the blood that builds up and crystallizes in the joints. Flare-ups are so intense that the joints can turn a cherry red and vibrate with intense – and sometimes seemingly intolerable – pain.

Dmytro Panchenko/iStockphoto

While there are effective treatments, many people fail to take their medications when they’re not in pain, and if the condition goes unchecked, it can get much worse and cause permanent damage to the joints.

“Gout can cause flare-ups that vary in frequency and severity; but sometimes when people aren’t experiencing them, they’re less likely to stay on top of their medications,” said Stephen Juraschek, MD, an assistant professor of medicine at Harvard Medical School, Boston.

That’s why lifestyle interventions are seen as particularly relevant to a disease like gout. Vitamin C, for example, has few side effects, and for those with higher levels of uric acid in the blood, it could reduce the likelihood of getting the condition. A recent study published in The American Journal of Clinical Nutrition found that people who were given 500 mg of vitamin C versus a placebo had a 12% reduced risk of getting gout. The study of over 14,000 male doctors showed that men who weren’t overweight had the most significant reduction in the risk of getting the condition. (Excess weight has been shown to increase the risk of gout.)

As part of the study, participants responded to a questionnaire that asked whether they had ever been diagnosed with gout. Other studies have shown that vitamin C reduced the levels of urate in people without gout and broke down uric crystals in the blood, but this study took it a step further to show that the supplement actually reduced the risk of getting the condition.

“In addition to lowering levels of uric acid in the body, it’s thought that vitamin C may also minimize the inflammatory response to urate crystals,” said Dr. Juraschek. That’s because when flare-ups develop in joints throughout the body, much of the painful irritation is caused by the immune system’s response as it fights to break down the crystals.

Dr. Juraschek said this likely wouldn’t change recommendations for patients with serious gout, but it could still have an impact.

“For individuals who were told that they have gout but have had fewer flare-ups, they might be more open to taking vitamin C,” he said.

Will Settle, 42, of Hilton Head, S.C., was not involved in the study, but he said he would be inclined to try most any safe preventive method. Gout runs in his family. His father and grandfather had it, and now, so does he. His flare-ups have slowed in recent years, which he said has a lot to do with his diet and lifestyle. He stopped eating seafood, started drinking more water, and stopped drinking as much alcohol – all of which he thinks has had a huge impact on the severity of his condition. (Both seafood and beer contain high levels of purines, which have been shown to increase the buildup of uric acid in the blood.) Mr. Settle said that other simple lifestyle changes like vitamin C would be an easy addition to his routine with few downsides. Plus, he hates having to take colchicine, a medication that’s meant to relieve pain but causes him intense diarrhea when he takes it.

“Anything to reduce my flare-ups without having to take colchicine,” he said.

But the jury is still out as to whether vitamin C will have any real benefits. Study coauthor Robert H. Shmerling, MD, is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center, New York. He said the study shows that the effect of vitamin C in those undiagnosed with gout was rather modest. Also, vitamin C did not show a reduction in gout flare-ups in those who were already diagnosed with the condition. Not to mention that the study lacked diversity, as the people in it were all male and mostly white. Still, there’s little downside risk to taking vitamin C, and it might end up being worthwhile.

“Maybe it will turn out to be an effective treatment in those who are at high risk, but we’re not there yet,” he said.

Robert Terkeltaub, MD, chief of rheumatology at the Veterans Administration Medical Center in San Diego and a professor of medicine at the University of California, San Diego, said there’s an unmet need when it comes to tools for gout prevention.

“The disease impacts some 10 million Americans, and we need to better identify these individuals so we can intervene earlier,” he said.

While vitamin C had a small but significant association with fewer new cases of gout, it did not lower it in those who already had the disease, said Dr. Terkeltaub. What’s more, researchers didn’t measure the levels of uric acid in the blood, which would have painted a more accurate picture of whether vitamin C actually reduced it in the body.

“There remains no clarity on the potential role of vitamin C in either prevention or treatment of gout. That said, future research would be of interest,” he said.

Still, gout patients like Mr. Settle aren’t ruling it out. Anything to avoid the pain that, at times, makes it difficult for him to get out of bed. He’s seen the benefit that simple lifestyle changes can make, and he’s willing to try just about anything to live a normal, arthritis-free life.

“I’m always looking for simple ways to keep my flare-ups at bay,” he said.

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

Could taking vitamin C help reduce the chances of developing gout? A new study sheds light on this possibility.

Gout is a form of inflammatory arthritis that has been on the rise in the United States in recent decades. Considered a lifestyle disease, some research has shown that instances of the condition have more than doubled in recent years as rates of obesity have skyrocketed. It’s caused by uric acid in the blood that builds up and crystallizes in the joints. Flare-ups are so intense that the joints can turn a cherry red and vibrate with intense – and sometimes seemingly intolerable – pain.

Dmytro Panchenko/iStockphoto

While there are effective treatments, many people fail to take their medications when they’re not in pain, and if the condition goes unchecked, it can get much worse and cause permanent damage to the joints.

“Gout can cause flare-ups that vary in frequency and severity; but sometimes when people aren’t experiencing them, they’re less likely to stay on top of their medications,” said Stephen Juraschek, MD, an assistant professor of medicine at Harvard Medical School, Boston.

That’s why lifestyle interventions are seen as particularly relevant to a disease like gout. Vitamin C, for example, has few side effects, and for those with higher levels of uric acid in the blood, it could reduce the likelihood of getting the condition. A recent study published in The American Journal of Clinical Nutrition found that people who were given 500 mg of vitamin C versus a placebo had a 12% reduced risk of getting gout. The study of over 14,000 male doctors showed that men who weren’t overweight had the most significant reduction in the risk of getting the condition. (Excess weight has been shown to increase the risk of gout.)

As part of the study, participants responded to a questionnaire that asked whether they had ever been diagnosed with gout. Other studies have shown that vitamin C reduced the levels of urate in people without gout and broke down uric crystals in the blood, but this study took it a step further to show that the supplement actually reduced the risk of getting the condition.

“In addition to lowering levels of uric acid in the body, it’s thought that vitamin C may also minimize the inflammatory response to urate crystals,” said Dr. Juraschek. That’s because when flare-ups develop in joints throughout the body, much of the painful irritation is caused by the immune system’s response as it fights to break down the crystals.

Dr. Juraschek said this likely wouldn’t change recommendations for patients with serious gout, but it could still have an impact.

“For individuals who were told that they have gout but have had fewer flare-ups, they might be more open to taking vitamin C,” he said.

Will Settle, 42, of Hilton Head, S.C., was not involved in the study, but he said he would be inclined to try most any safe preventive method. Gout runs in his family. His father and grandfather had it, and now, so does he. His flare-ups have slowed in recent years, which he said has a lot to do with his diet and lifestyle. He stopped eating seafood, started drinking more water, and stopped drinking as much alcohol – all of which he thinks has had a huge impact on the severity of his condition. (Both seafood and beer contain high levels of purines, which have been shown to increase the buildup of uric acid in the blood.) Mr. Settle said that other simple lifestyle changes like vitamin C would be an easy addition to his routine with few downsides. Plus, he hates having to take colchicine, a medication that’s meant to relieve pain but causes him intense diarrhea when he takes it.

“Anything to reduce my flare-ups without having to take colchicine,” he said.

But the jury is still out as to whether vitamin C will have any real benefits. Study coauthor Robert H. Shmerling, MD, is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center, New York. He said the study shows that the effect of vitamin C in those undiagnosed with gout was rather modest. Also, vitamin C did not show a reduction in gout flare-ups in those who were already diagnosed with the condition. Not to mention that the study lacked diversity, as the people in it were all male and mostly white. Still, there’s little downside risk to taking vitamin C, and it might end up being worthwhile.

“Maybe it will turn out to be an effective treatment in those who are at high risk, but we’re not there yet,” he said.

Robert Terkeltaub, MD, chief of rheumatology at the Veterans Administration Medical Center in San Diego and a professor of medicine at the University of California, San Diego, said there’s an unmet need when it comes to tools for gout prevention.

“The disease impacts some 10 million Americans, and we need to better identify these individuals so we can intervene earlier,” he said.

While vitamin C had a small but significant association with fewer new cases of gout, it did not lower it in those who already had the disease, said Dr. Terkeltaub. What’s more, researchers didn’t measure the levels of uric acid in the blood, which would have painted a more accurate picture of whether vitamin C actually reduced it in the body.

“There remains no clarity on the potential role of vitamin C in either prevention or treatment of gout. That said, future research would be of interest,” he said.

Still, gout patients like Mr. Settle aren’t ruling it out. Anything to avoid the pain that, at times, makes it difficult for him to get out of bed. He’s seen the benefit that simple lifestyle changes can make, and he’s willing to try just about anything to live a normal, arthritis-free life.

“I’m always looking for simple ways to keep my flare-ups at bay,” he said.

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