Long COVID

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

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

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

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

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

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

Emerging ‘Menstrual Science’ Could Be Key

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

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

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

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

How Gender and Long COVID Intertwine

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

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

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

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

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

Sex-Specific Symptoms and Marginalized Communities

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

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

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

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

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

Where It All Leads

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

Emerging ‘Menstrual Science’ Could Be Key

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

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

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

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

How Gender and Long COVID Intertwine

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

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

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

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

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

Sex-Specific Symptoms and Marginalized Communities

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

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

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

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

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

Where It All Leads

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

Emerging ‘Menstrual Science’ Could Be Key

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

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

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

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

How Gender and Long COVID Intertwine

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

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

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

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

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

Sex-Specific Symptoms and Marginalized Communities

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

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

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

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

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

Where It All Leads

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

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

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

A version of this article appeared on WebMD.com.

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

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

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

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

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

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

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

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

A version of this article appeared on WebMD.com.

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

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

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

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

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

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

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

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

A version of this article appeared on WebMD.com.

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

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

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

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

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

Testing Across Continents

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

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

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

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

The Microclot Connection

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

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

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

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

Research Offers New Direction

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

Testing Across Continents

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

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

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

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

The Microclot Connection

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

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

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

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

Research Offers New Direction

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

Testing Across Continents

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

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

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

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

The Microclot Connection

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

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

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

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

Research Offers New Direction

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

Too Easy to Let Our Guard Down

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

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

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

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

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

Long COVID Treatments Showing Improvement — Slowly

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

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

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

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

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

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

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

Time Helps Healing — But Prompt Care Still Needed

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

Too Easy to Let Our Guard Down

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

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

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

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

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

Long COVID Treatments Showing Improvement — Slowly

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

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

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

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

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

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

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

Time Helps Healing — But Prompt Care Still Needed

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

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

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

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

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

Too Easy to Let Our Guard Down

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

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

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

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

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

Long COVID Treatments Showing Improvement — Slowly

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

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

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

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

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

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

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

Time Helps Healing — But Prompt Care Still Needed

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

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

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

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

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

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

A version of this article appeared on Medscape.com.

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

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

Another Great Pretender?

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

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

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

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

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

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

Human intelligence source Wikipedia says this:

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

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

Acute COVID to Long COVID

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

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

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

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

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

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

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

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

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

Useful Progress?

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

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

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

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

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

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

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

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

Another Great Pretender?

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

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

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

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

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

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

Human intelligence source Wikipedia says this:

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

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

Acute COVID to Long COVID

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

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

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

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

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

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

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

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

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

Useful Progress?

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

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

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

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

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

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

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

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

Another Great Pretender?

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

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

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

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

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

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

Human intelligence source Wikipedia says this:

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

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

Acute COVID to Long COVID

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

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

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

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

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

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

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

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

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

Useful Progress?

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

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

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

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

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

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

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.

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

Annette Gillaspie, a nurse in a small Oregon hospital, hoped she would be back working with patients by now. She contracted COVID-19 on the job early in the pandemic and ended up with long COVID.

After recovering a bit, her fatigue and dizziness returned, and today she is still working a desk job. She has also experienced more severe menstrual periods than before she had COVID.

“Being a female with long COVID definitely does add to the roller-coaster effect of symptoms,” Ms. Gillaspie said.

Long COVID affects nearly twice as many women as men, with 6.6% of women reporting long COVID compared with 4% of men, according to a recent Census Bureau survey reported by the Centers for Disease Control and Prevention (CDC). Researchers are trying to determine why, what causes the gender disparity, and how best to treat it.

Scientists are also starting to look at the impact of long COVID on female reproductive health, including menstruation, pregnancy, and menopause.

Sex differences are common in infection-associated illnesses, said Beth Pollack, MS, a research scientist specializing in long COVID in the Massachusetts Institute of Technology’s Department of Biological Engineering, Cambridge, Massachusetts. “It informs research priorities and the lens with which we understand long COVID.”

For example, reproductive health issues for women, such as puberty, pregnancy, and menopause, can alter the course of illness in a subset of women in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and postural orthostatic tachycardia syndrome (POTS), a condition that can cause dizziness and worse.

“This suggests that sex hormones may play key roles in immune responses to infections,” Ms. Pollack said.

ME/CFS and a Possible Link to Long COVID in Women

Some of the research into long COVID is being led by teams studying infection-associated chronic illnesses like ME/CFS.

The problem: Advocates say ME/CFS has been under-researched. Poorly understood for years, the condition is one of a handful of chronic illnesses linked to infections, including Lyme disease and now long COVID. Perhaps not coincidently, they are more likely to affect women.

Many of the research findings about long COVID mirror data that emerged in past ME/CFS research, said Jaime Seltzer, the scientific director at #MEAction, Santa Monica, California, an advocacy group. One point in particular: ME/CFS strikes women about twice as much as men, according to the CDC.

Ms. Seltzer said the response to long COVID could be much further ahead if the research community acknowledged the work done over the years on ME/CFS. Many of the potential biomarkers and risk factors emerging for long COVID were also suspected in ME/CFS, but not thoroughly studied, she said.

She also said not enough work has been done to unravel the links between gender and these chronic conditions.

“We’re stuck in this Groundhog Day situation,” she said. “There isn’t any research, so we can’t say anything definitively.”

Some New Research, Some New Clues

Scientists like Ms. Pollack are slowly making inroads. She was lead author on a 2023 review investigating the impact of long COVID on female reproductive health. The paper highlights long COVID links to ME/CFS, POTS, and Ehlers-Danlos syndrome (EDS), as well as a resulting laundry list of female reproductive health issues. The hope is physicians will examine how the menstrual cycle, pregnancy, and menopause affect symptoms and illness progression of long COVID.

The Tal Research group at MIT (where Ms. Pollack works) has also added long COVID to the list of infection-associated illnesses it studies. The lab is conducting a large study looking into both Lyme disease and long COVID. The goals are to identify biomarkers that can predict who will not recover and to advance available treatments.

Another MIT program, “SEXX + Immunity” holds seminars and networking sessions for scientists looking into the role of female and male biology in immune responses to infection.

Barriers to Progress Remain

On the clinical side, female patients with long COVID also have to deal with a historical bias that still lurks in medicine when it comes to women’s health, said Alba Azola, MD, an assistant professor of physical medicine at Johns Hopkins Medicine, Baltimore, Maryland.

Dr. Azola said she has discovered clinical descriptions of ME/CFE in the literature archives that describe it as “neurasthenia” and dismiss it as psychological.

Patients say that it is still happening, and while it may not be so blunt, “you can read between the lines,” Dr. Azola said.

Dr. Azola, who has worked with long COVID patients and is now seeing people with ME/CFS, said the symptoms of infection-associated chronic illness can mimic menopause, and many of her patients received that misdiagnosis. She recommends that doctors rule out long COVID for women with multiple symptoms before attributing symptoms to menopause.

Seeing that some long COVID patients were developing ME/CFS, staff at the Bateman Horne Center in Salt Lake City, Utah, set up a program for the condition in 2021. They were already treating patients with ME/CFS and what they call “multi-symptom chronic complex diseases.”

Jennifer Bell, a certified nurse practitioner at the center, said she has not seen any patients with ovarian failure but plenty with reproductive health issues.

“There definitely is a hormonal connection, but I don’t think there’s a good understanding about what is happening,” she said.

Most of her patients are female, and the more serious patients tend to go through a worsening of their symptoms in the week prior to getting a period, she said.

One thing Ms. Bell said she’s noticed in the past year is an increase in patients with EDS, which is also more common in women.

Like long COVID, many of the conditions traditionally treated at the center have no cure. But Ms. Bell said the center has developed an expertise in treating post-exertional malaise, a common symptom of long COVID, and keeps up with the literature for treatments to try, like the combination of guanfacine and the antioxidant N-acetyl cysteine to treat brain fog, an approach developed at Yale.

“It’s a very challenging illness to treat,” Ms. Bell said.

Since the emergence of long COVID, researchers have warned that symptoms vary so much from person to person that treatment will need to be targeted.

Ms. Pollack of MIT agrees and sees a big role for personalized medicine.

We need to “identify phenotypes within and across these overlapping and co-occurring illnesses so that we can identify the right therapeutics for each person,” she said.

As for Annette Gillaspie, she still hopes her long COVID will subside so she can get out from behind the desk and return to her normal nursing duties.

“I just got to a point where I realized I’m likely never going to be able to do my job,” she said. “It was incredibly heart breaking, but it’s the reality of long COVID, and I know I’m not the only one to have to step away from a job I loved.”

A version of this article appeared on Medscape.com.

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

You may have never heard of it, but you may have had it. More evidence points to “long flu” being a real phenomenon, with a large study showing symptoms persist at least 4 weeks or more after some people are hospitalized for the flu.

Researchers compared long flu to long COVID-19 and found long flu happened less often and was less severe overall. This difference could be because the flu mostly affects the lungs whereas COVID can affect any number of organ systems in the body.

The investigators were surprised that both long flu and long COVID were linked to a greater burden of health loss, compared to either initial infection.

“I think COVID and long COVID made us realize that infections have long-term consequences, and often the toll of those long-term consequences is much larger than the toll of acute disease,” said Ziyad Al-Aly, MD, senior author of the study and chief of research and development at the VA St. Louis Health Care System.

“I know, having studied long COVID for the past 4 years, I should not be surprised. But I am in awe of what these infections can do to the long-term health of affected individuals,” said Dr. Al-Aly, who is also a clinical epidemiologist at Washington University in St. Louis.

Dr. Al-Aly and colleagues Yan Xie, PhD, and Taeyoung Choi, MS, analyzed US Department of Veterans Affairs medical records. They compared 81,280 people hospitalized with COVID to 10,985 people hospitalized with the flu before the COVID pandemic. They checked up to 18 months after initial infections to see who developed long flu or long COVID symptoms.

The study was published online in The Lancet Infectious Diseases.

It’s an interesting study, said Aaron E. Glatt, MD, chairman of the Department of Medicine and a hospital epidemiologist at Mount Sinai South Nassau in Oceanside, NY, who was not part of the research.

“There is a concern with many viruses that you can have long-term consequences,” said Dr. Glatt, who is also a fellow of the Infectious Diseases Society of America. He said the possibility of long-term symptoms with the flu is not new, “but it’s nice to have more data.”

People hospitalized with COVID had a 50% higher risk of death during the study period than people hospitalized with the flu. Put another way, for every 100 people admitted to the hospital with COVID, about eight more died than those hospitalized with the flu over the following 18 months. Hospital admissions and admissions to the intensive care unit were also higher in the long COVID group — 20 more people and nine more people, respectively, for every 100 people admitted to the hospital with COVID.

More research is needed, Dr. Glatt said. “With many of these viruses, we don’t understand what they do to the body.” A prospective study to see if antiviral treatments make a difference, for example, would be useful, he noted.

Dr. Al-Aly and colleagues would like to do more studies.

“We need to more deeply understand how and why acute infections cause long-term illness,” he said, noting that he also wants to investigate ways to prevent and treat the long-term effects.

“Much remains to be done, and we are deeply committed to doing our best to develop those answers.”

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

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.

While COVID has now claimed more than 1 million lives in the United States alone, these aren’t the only fatalities caused at least in part by the virus. A small but growing number of Americans are surviving acute infections only to succumb months later to the lingering health problems caused by long COVID.

Much of the attention on long COVID has centered on the sometimes debilitating symptoms that strike people with the condition, with no formal diagnostic tests or standard treatments available, and the effect it has on quality of life. But new figures from the US Centers for Disease Control and Prevention (CDC) show that long COVID can also be deadly.

More than 5000 Americans have died from long COVID since the start of the pandemic, according to new estimates from the CDC.

This total, based on death certificate data collected by the CDC, includes a preliminary tally of 1491 long COVID deaths in 2023 in addition to 3544 fatalities previously reported from January 2020 through June 2022.

Guidance issued in 2023 on how to formally report long COVID as a cause of death on death certificates should help get a more accurate count of these fatalities going forward, said Robert Anderson, PhD, chief mortality statistician for the CDC, Atlanta, Georgia.

“We hope that the guidance will help cause of death certifiers be more aware of the impact of long COVID and more likely to report long COVID as a cause of death when appropriate,” Dr. Anderson said. “That said, we do not expect that this guidance will have a dramatic impact on the trend.”

There’s no standard definition or diagnostic test for long COVID. It’s typically diagnosed when people have symptoms at least 3 months after an acute infection that weren’t present before they got sick. As of the end of last year, about 7% of American adults had experienced long COVID at some point, the CDC estimated in September 2023.

The new death tally indicates long COVID remains a significant public health threat and is likely to grow in the years ahead, even though the pandemic may no longer be considered a global health crisis, experts said.

For example, the death certificate figures indicate:

COVID-19 was the third leading cause of American deaths in 2020 and 2021, and the fourth leading cause of death in the United States in 2023.

Nearly 1% of the more than one million deaths related to COVID-19 since the start of the pandemic have been attributed to long COVID, according to data released by the CDC.

The proportion of COVID-related deaths from long COVID peaked in June 2021 at 1.2% and again in April 2022 at 3.8%, according to the CDC. Both of these peaks coincided with periods of declining fatalities from acute infections.

“I do expect that deaths associated with long COVID will make up an increasingly larger proportion of total deaths associated with COVID-19,” said Mark Czeisler, PhD, a researcher at Harvard Medical School, Boston, Massachusetts, who has studied long COVID fatalities. 

Months and even years after an acute infection, long COVID can contribute to serious and potentially life-threatening conditions that impact nearly every major system in the body, according to the CDC guidelines for identifying the condition on death certificates. 

This means long COVID may often be listed as an underlying cause of death when people with this condition die of issues related to their heart, lungs, brain or kidneys, the CDC guidelines noted.

The risk for long COVID fatalities remains elevated for at least 6 months for people with milder acute infections and for at least 2 years in severe cases that require hospitalization, some previous research suggested.

As happens with other acute infections, certain people are more at risk for fatal case of long COVID. Age, race, and ethnicity have all been cited as risk factors by researchers who have been tracking the condition since the start of the pandemic.

Half of long COVID fatalities from July 2021 to June 2022 occurred in people aged 65 years and older, and another 23% were recorded among people aged 50-64 years old, according a report from CDC.

Long COVID death rates also varied by race and ethnicity, from a high of 14.1 cases per million among America Indian and Alaskan natives to a low of 1.5 cases per million among Asian people, the CDC found. Death rates per million were 6.7 for White individuals, 6.4 for Black people, and 4.7 for Hispanic people.

The disproportionate share of Black and Hispanic people who developed and died from severe acute infections may have left fewer survivors to develop long COVID, limiting long COVID fatalities among these groups, the CDC report concluded.

It’s also possible that long COVID fatalities were undercounted in these populations because they faced challenges accessing healthcare or seeing providers who could recognize the hallmark symptoms of long COVID.

It’s also difficult to distinguish between how many deaths related to the virus ultimately occur as a result of long COVID rather than acute infections. That’s because it may depend on a variety of factors, including how consistently medical examiners follow the CDC guidelines, said Ziyad Al-Aly, MD, chief of research at the Veterans Affairs, St. Louis Health Care System and a senior clinical epidemiologist at Washington University in St. Louis.

“Long COVID remains massively underdiagnosed, and death in people with long COVID is misattributed to other things,” Dr. Al-Aly said.

An accurate test for long COVID could help lead to a more accurate count of these fatalities, Dr. Czeisler said. Some preliminary research suggests that it might one day be possible to diagnose long COVID with a blood test.

“The timeline for such a test and the extent to which it would be widely applied is uncertain,” Dr. Czeisler noted, “though that would certainly be a gamechanger.”

A version of this article appeared on Medscape.com.