Residents

A new broadly inclusive definition of long COVID from the National Academies of Sciences, Engineering, and Medicine (NASEM) has been developed with the aim of improving consistency, documentation, and treatment for both adults and children.

According to the 2024 NASEM definition of long COVID issued on June 11, 2024, “Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.” 

People with long COVID may present with one or more of a long list of symptoms, such as shortness of breath, rapid heartbeat, extreme fatigue, post-exertional malaise, or sleep disturbance and with single or multiple diagnosable conditions, including interstitial lung disease, arrhythmias, postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), diabetes, or autoimmune disorders. The condition can exacerbate preexisting health conditions or present as new ones. 

The definition does not require laboratory confirmation or other proof of initial infection. Long COVID can follow SARS-CoV-2 infection of any severity, including asymptomatic infections, whether or not they were initially recognized. 

Several working definitions and terms for long COVID had previously been proposed, including those from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention, but no common definition or terminology had been established.

The new definition was developed at the request of the Administration for Strategic Preparedness and Response and the Office of the Assistant Secretary for Health (OASH). It was written by a multi-stakeholder panel convened by NASEM, which recommended that the new definition be universally adopted by the federal government, clinical societies and associations, public health practitioners, clinicians, payers, the drug industry, and others using the term long COVID. 

Recent surveys suggest that approximately 7% of Americans have experienced or are experiencing long COVID. “It’s millions of people,” panel chair Harvey V. Fineberg, MD, president of the Gordon and Betty Moore Foundation, told this news organization. 

The new definition “does not erase the problem of clinical judgment ... But we think this definition has the real advantage of elevating to the clinician’s mind the real likelihood in the current environment of prevalence of this virus that a presenting patient’s strange symptoms are both real and maybe related as an expression of long COVID,” Dr. Fineberg noted. 

One way this new definition differs from previous ones such as WHO’s, he said, is “they talk about a diagnosis of exclusion. One of the important points in our definition is that other diagnosable conditions like ME/CFS or POTS can be part of the picture of long COVID. They are not alternative. They are, in fact, an expression of long COVID.”

Indeed, the NASEM report also introduces the term infection-associated chronic condition (IACC). This was important, Dr. Fineberg said, “because it’s the larger family of conditions of which long COVID is a part. It emphasizes a relatedness of long COVID to other conditions that can follow from a variety of infections. We also adopted the term ‘disease state’ to convey the seriousness and reality of this condition in the lives of patients.” 
 

Comments on New Definition

In a statement provided to this news organization, Lucinda Bateman, MD, and Brayden Yellman, MD, co-medical directors of the Bateman-Horne Center in Salt Lake City, said that “describing long COVID as an IACC ... not only meets the NASEM goal of allowing clinicians, researchers, and public health officials to meaningfully identify and serve all persons who suffer illness or disability in the wake of a SARS-CoV-2 infection, but also draws direct comparison to other known IACC’s (such as ME/CFS, post-treatment Lyme, POTS) that have been plaguing many for decades.”

Dr. Fineberg noted another important aspect of the NASEM report: “Our definition includes an explicit statement on equity, explaining that long COVID can affect anyone, young and old, different races, different ages, different sexes, different genders, different orientations, different socioeconomic conditions ... This does not mean that every single person is at equal risk. There are risk factors, but the important point is the universal nature of this as a condition.”

Two clinical directors of long COVID programs who were contacted by this news organization praised the new definition. Zijian Chen, MD, director of Mount Sinai’s Center for Post-COVID Care, New York, said that it’s “very similar to the definition that we have used for our clinical practice since 2020. It is very important that the broad definition helps to be inclusive of all patients that may be affected. The inclusion of children as a consideration is important as well, since there is routinely less focus on children because they tend to have less disease frequency ... The creation of a unified definition helps both with clinical practice and research.”

Nisha Viswanathan, MD, director of the long COVID program at the University of California, Los Angeles, said: “I think they left it intentionally broad for the medical practitioner to not necessarily use the definition to rule out individuals, but to perhaps use more of a clinical gestalt to help rule in this diagnosis ... I think this definition is providing clarity to health care providers on what exactly would be falling under the long-COVID diagnosis header.” 

Dr. Viswanathan also said that she anticipates this definition to help patients make their case in filing disability claims. “Because long COVID has not previously had a good fleshed-out definition, it was very easy for disability providers to reject claims for patients who continue to have symptoms ... I actually think this might help our patients ultimately in their attempt to be able to have the ability to care for themselves when they’re disabled enough to not be able to work.”

Written into the report is the expectation that the definition “will evolve as new evidence emerges and the understanding of long COVID matures.” The writing committee calls for reexamination in “no more than 3 years.” Factors that would prompt a reevaluation could include improved testing methods, discovery of medical factors and/or biomarkers that distinguish long COVID from other conditions, and new treatments. 

Meanwhile, Dr. Fineberg told this news organization, “If this definition adds to the readiness, awareness, openness, and response to the patient with long COVID, it will have done its job.” 

Dr. Fineberg, Dr. Bateman, Dr. Yellman, Dr. Viswanathan, and Dr. Chen have no relevant disclosures.

A version of this article appeared on Medscape.com.

A new broadly inclusive definition of long COVID from the National Academies of Sciences, Engineering, and Medicine (NASEM) has been developed with the aim of improving consistency, documentation, and treatment for both adults and children.

According to the 2024 NASEM definition of long COVID issued on June 11, 2024, “Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.” 

People with long COVID may present with one or more of a long list of symptoms, such as shortness of breath, rapid heartbeat, extreme fatigue, post-exertional malaise, or sleep disturbance and with single or multiple diagnosable conditions, including interstitial lung disease, arrhythmias, postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), diabetes, or autoimmune disorders. The condition can exacerbate preexisting health conditions or present as new ones. 

The definition does not require laboratory confirmation or other proof of initial infection. Long COVID can follow SARS-CoV-2 infection of any severity, including asymptomatic infections, whether or not they were initially recognized. 

Several working definitions and terms for long COVID had previously been proposed, including those from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention, but no common definition or terminology had been established.

The new definition was developed at the request of the Administration for Strategic Preparedness and Response and the Office of the Assistant Secretary for Health (OASH). It was written by a multi-stakeholder panel convened by NASEM, which recommended that the new definition be universally adopted by the federal government, clinical societies and associations, public health practitioners, clinicians, payers, the drug industry, and others using the term long COVID. 

Recent surveys suggest that approximately 7% of Americans have experienced or are experiencing long COVID. “It’s millions of people,” panel chair Harvey V. Fineberg, MD, president of the Gordon and Betty Moore Foundation, told this news organization. 

The new definition “does not erase the problem of clinical judgment ... But we think this definition has the real advantage of elevating to the clinician’s mind the real likelihood in the current environment of prevalence of this virus that a presenting patient’s strange symptoms are both real and maybe related as an expression of long COVID,” Dr. Fineberg noted. 

One way this new definition differs from previous ones such as WHO’s, he said, is “they talk about a diagnosis of exclusion. One of the important points in our definition is that other diagnosable conditions like ME/CFS or POTS can be part of the picture of long COVID. They are not alternative. They are, in fact, an expression of long COVID.”

Indeed, the NASEM report also introduces the term infection-associated chronic condition (IACC). This was important, Dr. Fineberg said, “because it’s the larger family of conditions of which long COVID is a part. It emphasizes a relatedness of long COVID to other conditions that can follow from a variety of infections. We also adopted the term ‘disease state’ to convey the seriousness and reality of this condition in the lives of patients.” 
 

Comments on New Definition

In a statement provided to this news organization, Lucinda Bateman, MD, and Brayden Yellman, MD, co-medical directors of the Bateman-Horne Center in Salt Lake City, said that “describing long COVID as an IACC ... not only meets the NASEM goal of allowing clinicians, researchers, and public health officials to meaningfully identify and serve all persons who suffer illness or disability in the wake of a SARS-CoV-2 infection, but also draws direct comparison to other known IACC’s (such as ME/CFS, post-treatment Lyme, POTS) that have been plaguing many for decades.”

Dr. Fineberg noted another important aspect of the NASEM report: “Our definition includes an explicit statement on equity, explaining that long COVID can affect anyone, young and old, different races, different ages, different sexes, different genders, different orientations, different socioeconomic conditions ... This does not mean that every single person is at equal risk. There are risk factors, but the important point is the universal nature of this as a condition.”

Two clinical directors of long COVID programs who were contacted by this news organization praised the new definition. Zijian Chen, MD, director of Mount Sinai’s Center for Post-COVID Care, New York, said that it’s “very similar to the definition that we have used for our clinical practice since 2020. It is very important that the broad definition helps to be inclusive of all patients that may be affected. The inclusion of children as a consideration is important as well, since there is routinely less focus on children because they tend to have less disease frequency ... The creation of a unified definition helps both with clinical practice and research.”

Nisha Viswanathan, MD, director of the long COVID program at the University of California, Los Angeles, said: “I think they left it intentionally broad for the medical practitioner to not necessarily use the definition to rule out individuals, but to perhaps use more of a clinical gestalt to help rule in this diagnosis ... I think this definition is providing clarity to health care providers on what exactly would be falling under the long-COVID diagnosis header.” 

Dr. Viswanathan also said that she anticipates this definition to help patients make their case in filing disability claims. “Because long COVID has not previously had a good fleshed-out definition, it was very easy for disability providers to reject claims for patients who continue to have symptoms ... I actually think this might help our patients ultimately in their attempt to be able to have the ability to care for themselves when they’re disabled enough to not be able to work.”

Written into the report is the expectation that the definition “will evolve as new evidence emerges and the understanding of long COVID matures.” The writing committee calls for reexamination in “no more than 3 years.” Factors that would prompt a reevaluation could include improved testing methods, discovery of medical factors and/or biomarkers that distinguish long COVID from other conditions, and new treatments. 

Meanwhile, Dr. Fineberg told this news organization, “If this definition adds to the readiness, awareness, openness, and response to the patient with long COVID, it will have done its job.” 

Dr. Fineberg, Dr. Bateman, Dr. Yellman, Dr. Viswanathan, and Dr. Chen have no relevant disclosures.

A version of this article appeared on Medscape.com.

A new broadly inclusive definition of long COVID from the National Academies of Sciences, Engineering, and Medicine (NASEM) has been developed with the aim of improving consistency, documentation, and treatment for both adults and children.

According to the 2024 NASEM definition of long COVID issued on June 11, 2024, “Long COVID is an infection-associated chronic condition that occurs after SARS-CoV-2 infection and is present for at least 3 months as a continuous, relapsing and remitting, or progressive disease state that affects one or more organ systems.” 

People with long COVID may present with one or more of a long list of symptoms, such as shortness of breath, rapid heartbeat, extreme fatigue, post-exertional malaise, or sleep disturbance and with single or multiple diagnosable conditions, including interstitial lung disease, arrhythmias, postural orthostatic tachycardia syndrome (POTS), myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), diabetes, or autoimmune disorders. The condition can exacerbate preexisting health conditions or present as new ones. 

The definition does not require laboratory confirmation or other proof of initial infection. Long COVID can follow SARS-CoV-2 infection of any severity, including asymptomatic infections, whether or not they were initially recognized. 

Several working definitions and terms for long COVID had previously been proposed, including those from the World Health Organization (WHO) and the US Centers for Disease Control and Prevention, but no common definition or terminology had been established.

The new definition was developed at the request of the Administration for Strategic Preparedness and Response and the Office of the Assistant Secretary for Health (OASH). It was written by a multi-stakeholder panel convened by NASEM, which recommended that the new definition be universally adopted by the federal government, clinical societies and associations, public health practitioners, clinicians, payers, the drug industry, and others using the term long COVID. 

Recent surveys suggest that approximately 7% of Americans have experienced or are experiencing long COVID. “It’s millions of people,” panel chair Harvey V. Fineberg, MD, president of the Gordon and Betty Moore Foundation, told this news organization. 

The new definition “does not erase the problem of clinical judgment ... But we think this definition has the real advantage of elevating to the clinician’s mind the real likelihood in the current environment of prevalence of this virus that a presenting patient’s strange symptoms are both real and maybe related as an expression of long COVID,” Dr. Fineberg noted. 

One way this new definition differs from previous ones such as WHO’s, he said, is “they talk about a diagnosis of exclusion. One of the important points in our definition is that other diagnosable conditions like ME/CFS or POTS can be part of the picture of long COVID. They are not alternative. They are, in fact, an expression of long COVID.”

Indeed, the NASEM report also introduces the term infection-associated chronic condition (IACC). This was important, Dr. Fineberg said, “because it’s the larger family of conditions of which long COVID is a part. It emphasizes a relatedness of long COVID to other conditions that can follow from a variety of infections. We also adopted the term ‘disease state’ to convey the seriousness and reality of this condition in the lives of patients.” 
 

Comments on New Definition

In a statement provided to this news organization, Lucinda Bateman, MD, and Brayden Yellman, MD, co-medical directors of the Bateman-Horne Center in Salt Lake City, said that “describing long COVID as an IACC ... not only meets the NASEM goal of allowing clinicians, researchers, and public health officials to meaningfully identify and serve all persons who suffer illness or disability in the wake of a SARS-CoV-2 infection, but also draws direct comparison to other known IACC’s (such as ME/CFS, post-treatment Lyme, POTS) that have been plaguing many for decades.”

Dr. Fineberg noted another important aspect of the NASEM report: “Our definition includes an explicit statement on equity, explaining that long COVID can affect anyone, young and old, different races, different ages, different sexes, different genders, different orientations, different socioeconomic conditions ... This does not mean that every single person is at equal risk. There are risk factors, but the important point is the universal nature of this as a condition.”

Two clinical directors of long COVID programs who were contacted by this news organization praised the new definition. Zijian Chen, MD, director of Mount Sinai’s Center for Post-COVID Care, New York, said that it’s “very similar to the definition that we have used for our clinical practice since 2020. It is very important that the broad definition helps to be inclusive of all patients that may be affected. The inclusion of children as a consideration is important as well, since there is routinely less focus on children because they tend to have less disease frequency ... The creation of a unified definition helps both with clinical practice and research.”

Nisha Viswanathan, MD, director of the long COVID program at the University of California, Los Angeles, said: “I think they left it intentionally broad for the medical practitioner to not necessarily use the definition to rule out individuals, but to perhaps use more of a clinical gestalt to help rule in this diagnosis ... I think this definition is providing clarity to health care providers on what exactly would be falling under the long-COVID diagnosis header.” 

Dr. Viswanathan also said that she anticipates this definition to help patients make their case in filing disability claims. “Because long COVID has not previously had a good fleshed-out definition, it was very easy for disability providers to reject claims for patients who continue to have symptoms ... I actually think this might help our patients ultimately in their attempt to be able to have the ability to care for themselves when they’re disabled enough to not be able to work.”

Written into the report is the expectation that the definition “will evolve as new evidence emerges and the understanding of long COVID matures.” The writing committee calls for reexamination in “no more than 3 years.” Factors that would prompt a reevaluation could include improved testing methods, discovery of medical factors and/or biomarkers that distinguish long COVID from other conditions, and new treatments. 

Meanwhile, Dr. Fineberg told this news organization, “If this definition adds to the readiness, awareness, openness, and response to the patient with long COVID, it will have done its job.” 

Dr. Fineberg, Dr. Bateman, Dr. Yellman, Dr. Viswanathan, and Dr. Chen have no relevant disclosures.

A version of this article appeared on Medscape.com.

Stuart Malcolm, MD, a primary care physician who practices in Oregon and northern California, started seeing patients with long COVID early in the pandemic. Back then, he was frustrated by the obstacles and lack of standard diagnostic tests and treatments. Four years later, well, he still is.

“Something I learned the last few years is the logistics to get people care is really, really hard,” he said. “There’s a lot of frustration. It’s mostly frustration.”

For long COVID doctors and patients, there has been little to no progress addressing the challenges, leaving many discouraged. Researchers and clinicians now have a greater understanding of what health agencies formally call post-COVID condition, but the wide spectrum of symptoms, slow progress in launching pharmacologic clinical trials, and the research toward understanding the underlying causes mean standardized diagnostic tests and definitive treatments remain elusive.

“The frustration is that we aren’t able to help everyone with our current knowledge base. And I think the frustration lies not just with us physicians but also with patients because they’re at the point where if they tried everything, literally everything and haven’t gotten better,” said Zijian Chen, MD, director of the Mount Sinai Center for Post-COVID Care in New York City.
 

Wanted: More Funding, More Doctors, More Clinics

Between 10% and 20% of the estimated hundreds of millions of people infected worldwide with SARS-CoV-2 in the first 2 years went on to develop long-term symptoms. While many recover over time, doctors who have treated long COVID since 2020 said they see some patients still wrestling with the condition after 4 years.

The latest Centers for Disease Control and Prevention Household Pulse Survey, taken between March 5 and April 1, 2024, estimated that nearly 7% of the adult population — more than 18 million people — currently have long COVID. Data from other countries also suggest that millions have been living with long COVID for years now, and hundreds of thousands have seen their day-to-day activities significantly affected.

There is an urgent need for more funding, long COVID clinicians, multidisciplinary clinics, and education for non–long COVID physicians and specialists, doctors said. Instead, funding remains limited, clinics are closing, wait times are “horrendously long,” patients are left in limbo, and physicians are burning out.

“What’s changed in some ways is that there’s even less access to COVID rehab, which sounds crazy because there was very little to begin with,” said Alexandra Rendely, MD, a physical medicine and rehabilitation physician with the interdisciplinary Toronto Rehab, a part of the University Health Network of teaching hospitals in Toronto, Ontario, Canada.

“Patients are still being diagnosed every day, yet the resources available are becoming less and less.”

COVID-19 money earmarked during the pandemic was mostly limited to temporary emergency measures. As those funds dwindled, governments and institutions have decreased financial support. The Long COVID Moonshot campaign, organized by patients with long COVID, is pushing Congress to support $1 billion in annual research funding to close the financial chasm.
 

The Clinical Trial Conundrum

While long COVID clinics have come a long way in helping patients, gaps remain. Doctors may be unwilling to prescribe off-label treatments without proper clinical trials due to the potential risks and liabilities involved or due to the controversial or unconventional nature of the therapies, said Dr. Malcolm, who left his primary care practice more than 2 years ago to focus on long COVID.

In the absence of standard treatments, Dr. Malcolm and other doctors said they must take a trial-and-error approach in treating patients with long COVID that centers on addressing symptoms and not the underlying condition.

“There are actually a lot of treatments and a lot of them are not curative, but they can help people,” he said.

Dr. Malcolm, who is a medical director at Real Time Health Monitoring, a private clinic in the San Francisco Bay Area that specializes in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), said it was important for him to be with a clinical team that understood and was supportive of his treatment decisions and was able to offer clinical support for those treatments if needed.

For physicians looking for clinical data before prescribing certain medications, the wait may be long. More than $1.5 billion in US federal funding has been earmarked to study long COVID, but the National Institutes of Health (NIH) has faced criticism from patients and scientists alike for its slow progress and emphasis on observational studies instead of research that could unravel the biological roots of long COVID. Among the clinical trials announced by the NIH’s RECOVER initiative, only a handful involve studying pharmaceutical treatments.

A 2023 editorial published in The Lancet called out the “dismal state of clinical research relative to the substantial burden of [long COVID]” and said, “we are clearly lacking tested pharmacological interventions that treat the underlying pathophysiology.” At the time of publication, it noted that of the 386 long COVID trials listed on ClinicalTrials.gov, only 12 were actually testing pharmacologic interventions.

There are also diagnostic and insurance barriers. The specialized tests that can detect long COVID anomalies are neither commonly known by primary care practitioners nor easily requested at the local lab, can be expensive, and are typically not covered by insurance, Dr. Malcolm explained.

Patients with long COVID also have the added barrier of being unable to advocate as easily because of their energy limitations, doctors said. Patients may appear outwardly fine, but fatigue and brain fog are among the many problems that cannot be measured in appearances. The condition has upended lives, some losing jobs, even homes, and the mental toll is why there is a “not insignificant” suicide rate.
 

One Patient’s 4-Year Journey

Charlie McCone, 34, used to be a tennis player and an active musician. But he’s spent the past 4 years mostly housebound, grappling with the aftermath of a SARS-CoV-2 infection he contracted in March 2020. He went from biking daily to work 10 miles and back to having at most 2 hours of energy per day.

In the first year alone, Mr. McCone saw more than two dozen doctors and specialists. The conditions now associated with long COVID, like ME/CFS, mast cell activation syndrome (a condition in which a patient experiences episodes of allergic symptoms such as hives, swelling, low blood pressure, and difficulty breathing), or dysautonomia (conditions that affect the autonomic nervous system, which controls automatic processes in the body) were not on physicians’ radars.

Then in 2021, he became bedbound for more than half a year after a Delta variant reinfection. He developed neurologic symptoms, including incapacitating fatigue, post-exertional malaise (where symptoms worsened after minimal physical or mental activity), left-sided weakness, and cognitive impairment. He stopped working altogether. But the worst was the shortness of breath he felt 24/7, even at rest. A battery of lab tests revealed nothing abnormal. He tried numerous drugs and the classic respiratory treatments.

Mr. McCone eventually connected with Dr. Malcolm over X and developed what he describes as an effective patient-doctor collaboration. When studies came out suggesting microclots were a common issue with patients with long COVID and positive outcomes were reported from anticoagulant therapy, they knew it could be one of the answers.

“After 3 weeks on [the antiplatelet drug], I was like, oh my god, my lungs are finally opening up,” said Mr. McCone. He has taken the medication for more than a year and a half, and some days he doesn’t even think about his respiratory symptoms.

“That trial-and-error process is just really long and hard and costly,” said Dr. Malcolm.

Today, fatigue and cognitive stamina are Mr. McCone’s main challenges, and he is far from recovered.

“[I had a] very fulfilling, happy life and now, it’s hard to think about. I’ve come a long way with my mental health and all this, but I’ve lost 4 years,” Mr. McCone said. “The prospect of me being here when I’m 40 seems very real ... so it’s pretty devastating.”
 

Lessons Learned, Hope Amid Ongoing Research

Despite the daunting obstacle, doctors said the science has come a long way for a new disease. We now know long COVID is likely caused by a combination of triggers, including viral reservoir in the tissue, inflammation, autoimmunity, and microclots; severity of infection is not necessarily an accurate risk factor predictor — long COVID can strike even those who had a mild infection; upward of 200 symptoms have been identified; and we know more about potential biomarkers that could lead to better diagnostic tools.

Unlike many other diseases and conditions with standard treatment protocols, long COVID treatments are typically aimed at addressing individual symptoms.

“It is very detailed and individualized to the patient’s specific symptoms and to the patient’s specific needs,” Dr. Rendely said. Symptoms can also fluctuate, relapse, or wax and wane, for example, so what ails a patient at their first doctor’s appointment could be completely different at the next appointment 2 months later.

Doctors are still hopeful the RECOVER research, which includes trials that look at autonomic and cognitive dysfunctions, will pave the way for more effective long COVID therapies. In Canada, Dr. Rendely is also eying the RECLAIM trial that is currently testing the effectiveness of pentoxifylline, which helps blood flow, and ibudilast, an anti-inflammatory drug.

Doctors are also hopeful when they see patients who have made “tremendous gains” or even full recoveries through their clinics. “It’s a new diagnosis, so I always tell my patients to think of this as a journey because I’m learning along with you,” said Jai Marathe, MD, an infectious disease physician at Boston Medical Center and an assistant professor of infectious diseases at Boston University Chobanian & Avedisian School of Medicine.

“Now we have 4 years of experience, but at the same time, no two long COVID patients are alike.”

Long COVID has also changed the way physicians view healthcare and how they practice medicine.

“I am a completely different person than I used to be because of this illness, and I don’t even have it. That is how profoundly it has affected how I view the universe,” said Dr. Malcolm. “I’ve been doing this for 4 years, and I’m very hopeful. But I don’t think about this in terms of months anymore. I think about this in terms of years.”

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

Stuart Malcolm, MD, a primary care physician who practices in Oregon and northern California, started seeing patients with long COVID early in the pandemic. Back then, he was frustrated by the obstacles and lack of standard diagnostic tests and treatments. Four years later, well, he still is.

“Something I learned the last few years is the logistics to get people care is really, really hard,” he said. “There’s a lot of frustration. It’s mostly frustration.”

For long COVID doctors and patients, there has been little to no progress addressing the challenges, leaving many discouraged. Researchers and clinicians now have a greater understanding of what health agencies formally call post-COVID condition, but the wide spectrum of symptoms, slow progress in launching pharmacologic clinical trials, and the research toward understanding the underlying causes mean standardized diagnostic tests and definitive treatments remain elusive.

“The frustration is that we aren’t able to help everyone with our current knowledge base. And I think the frustration lies not just with us physicians but also with patients because they’re at the point where if they tried everything, literally everything and haven’t gotten better,” said Zijian Chen, MD, director of the Mount Sinai Center for Post-COVID Care in New York City.
 

Wanted: More Funding, More Doctors, More Clinics

Between 10% and 20% of the estimated hundreds of millions of people infected worldwide with SARS-CoV-2 in the first 2 years went on to develop long-term symptoms. While many recover over time, doctors who have treated long COVID since 2020 said they see some patients still wrestling with the condition after 4 years.

The latest Centers for Disease Control and Prevention Household Pulse Survey, taken between March 5 and April 1, 2024, estimated that nearly 7% of the adult population — more than 18 million people — currently have long COVID. Data from other countries also suggest that millions have been living with long COVID for years now, and hundreds of thousands have seen their day-to-day activities significantly affected.

There is an urgent need for more funding, long COVID clinicians, multidisciplinary clinics, and education for non–long COVID physicians and specialists, doctors said. Instead, funding remains limited, clinics are closing, wait times are “horrendously long,” patients are left in limbo, and physicians are burning out.

“What’s changed in some ways is that there’s even less access to COVID rehab, which sounds crazy because there was very little to begin with,” said Alexandra Rendely, MD, a physical medicine and rehabilitation physician with the interdisciplinary Toronto Rehab, a part of the University Health Network of teaching hospitals in Toronto, Ontario, Canada.

“Patients are still being diagnosed every day, yet the resources available are becoming less and less.”

COVID-19 money earmarked during the pandemic was mostly limited to temporary emergency measures. As those funds dwindled, governments and institutions have decreased financial support. The Long COVID Moonshot campaign, organized by patients with long COVID, is pushing Congress to support $1 billion in annual research funding to close the financial chasm.
 

The Clinical Trial Conundrum

While long COVID clinics have come a long way in helping patients, gaps remain. Doctors may be unwilling to prescribe off-label treatments without proper clinical trials due to the potential risks and liabilities involved or due to the controversial or unconventional nature of the therapies, said Dr. Malcolm, who left his primary care practice more than 2 years ago to focus on long COVID.

In the absence of standard treatments, Dr. Malcolm and other doctors said they must take a trial-and-error approach in treating patients with long COVID that centers on addressing symptoms and not the underlying condition.

“There are actually a lot of treatments and a lot of them are not curative, but they can help people,” he said.

Dr. Malcolm, who is a medical director at Real Time Health Monitoring, a private clinic in the San Francisco Bay Area that specializes in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), said it was important for him to be with a clinical team that understood and was supportive of his treatment decisions and was able to offer clinical support for those treatments if needed.

For physicians looking for clinical data before prescribing certain medications, the wait may be long. More than $1.5 billion in US federal funding has been earmarked to study long COVID, but the National Institutes of Health (NIH) has faced criticism from patients and scientists alike for its slow progress and emphasis on observational studies instead of research that could unravel the biological roots of long COVID. Among the clinical trials announced by the NIH’s RECOVER initiative, only a handful involve studying pharmaceutical treatments.

A 2023 editorial published in The Lancet called out the “dismal state of clinical research relative to the substantial burden of [long COVID]” and said, “we are clearly lacking tested pharmacological interventions that treat the underlying pathophysiology.” At the time of publication, it noted that of the 386 long COVID trials listed on ClinicalTrials.gov, only 12 were actually testing pharmacologic interventions.

There are also diagnostic and insurance barriers. The specialized tests that can detect long COVID anomalies are neither commonly known by primary care practitioners nor easily requested at the local lab, can be expensive, and are typically not covered by insurance, Dr. Malcolm explained.

Patients with long COVID also have the added barrier of being unable to advocate as easily because of their energy limitations, doctors said. Patients may appear outwardly fine, but fatigue and brain fog are among the many problems that cannot be measured in appearances. The condition has upended lives, some losing jobs, even homes, and the mental toll is why there is a “not insignificant” suicide rate.
 

One Patient’s 4-Year Journey

Charlie McCone, 34, used to be a tennis player and an active musician. But he’s spent the past 4 years mostly housebound, grappling with the aftermath of a SARS-CoV-2 infection he contracted in March 2020. He went from biking daily to work 10 miles and back to having at most 2 hours of energy per day.

In the first year alone, Mr. McCone saw more than two dozen doctors and specialists. The conditions now associated with long COVID, like ME/CFS, mast cell activation syndrome (a condition in which a patient experiences episodes of allergic symptoms such as hives, swelling, low blood pressure, and difficulty breathing), or dysautonomia (conditions that affect the autonomic nervous system, which controls automatic processes in the body) were not on physicians’ radars.

Then in 2021, he became bedbound for more than half a year after a Delta variant reinfection. He developed neurologic symptoms, including incapacitating fatigue, post-exertional malaise (where symptoms worsened after minimal physical or mental activity), left-sided weakness, and cognitive impairment. He stopped working altogether. But the worst was the shortness of breath he felt 24/7, even at rest. A battery of lab tests revealed nothing abnormal. He tried numerous drugs and the classic respiratory treatments.

Mr. McCone eventually connected with Dr. Malcolm over X and developed what he describes as an effective patient-doctor collaboration. When studies came out suggesting microclots were a common issue with patients with long COVID and positive outcomes were reported from anticoagulant therapy, they knew it could be one of the answers.

“After 3 weeks on [the antiplatelet drug], I was like, oh my god, my lungs are finally opening up,” said Mr. McCone. He has taken the medication for more than a year and a half, and some days he doesn’t even think about his respiratory symptoms.

“That trial-and-error process is just really long and hard and costly,” said Dr. Malcolm.

Today, fatigue and cognitive stamina are Mr. McCone’s main challenges, and he is far from recovered.

“[I had a] very fulfilling, happy life and now, it’s hard to think about. I’ve come a long way with my mental health and all this, but I’ve lost 4 years,” Mr. McCone said. “The prospect of me being here when I’m 40 seems very real ... so it’s pretty devastating.”
 

Lessons Learned, Hope Amid Ongoing Research

Despite the daunting obstacle, doctors said the science has come a long way for a new disease. We now know long COVID is likely caused by a combination of triggers, including viral reservoir in the tissue, inflammation, autoimmunity, and microclots; severity of infection is not necessarily an accurate risk factor predictor — long COVID can strike even those who had a mild infection; upward of 200 symptoms have been identified; and we know more about potential biomarkers that could lead to better diagnostic tools.

Unlike many other diseases and conditions with standard treatment protocols, long COVID treatments are typically aimed at addressing individual symptoms.

“It is very detailed and individualized to the patient’s specific symptoms and to the patient’s specific needs,” Dr. Rendely said. Symptoms can also fluctuate, relapse, or wax and wane, for example, so what ails a patient at their first doctor’s appointment could be completely different at the next appointment 2 months later.

Doctors are still hopeful the RECOVER research, which includes trials that look at autonomic and cognitive dysfunctions, will pave the way for more effective long COVID therapies. In Canada, Dr. Rendely is also eying the RECLAIM trial that is currently testing the effectiveness of pentoxifylline, which helps blood flow, and ibudilast, an anti-inflammatory drug.

Doctors are also hopeful when they see patients who have made “tremendous gains” or even full recoveries through their clinics. “It’s a new diagnosis, so I always tell my patients to think of this as a journey because I’m learning along with you,” said Jai Marathe, MD, an infectious disease physician at Boston Medical Center and an assistant professor of infectious diseases at Boston University Chobanian & Avedisian School of Medicine.

“Now we have 4 years of experience, but at the same time, no two long COVID patients are alike.”

Long COVID has also changed the way physicians view healthcare and how they practice medicine.

“I am a completely different person than I used to be because of this illness, and I don’t even have it. That is how profoundly it has affected how I view the universe,” said Dr. Malcolm. “I’ve been doing this for 4 years, and I’m very hopeful. But I don’t think about this in terms of months anymore. I think about this in terms of years.”

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

Stuart Malcolm, MD, a primary care physician who practices in Oregon and northern California, started seeing patients with long COVID early in the pandemic. Back then, he was frustrated by the obstacles and lack of standard diagnostic tests and treatments. Four years later, well, he still is.

“Something I learned the last few years is the logistics to get people care is really, really hard,” he said. “There’s a lot of frustration. It’s mostly frustration.”

For long COVID doctors and patients, there has been little to no progress addressing the challenges, leaving many discouraged. Researchers and clinicians now have a greater understanding of what health agencies formally call post-COVID condition, but the wide spectrum of symptoms, slow progress in launching pharmacologic clinical trials, and the research toward understanding the underlying causes mean standardized diagnostic tests and definitive treatments remain elusive.

“The frustration is that we aren’t able to help everyone with our current knowledge base. And I think the frustration lies not just with us physicians but also with patients because they’re at the point where if they tried everything, literally everything and haven’t gotten better,” said Zijian Chen, MD, director of the Mount Sinai Center for Post-COVID Care in New York City.
 

Wanted: More Funding, More Doctors, More Clinics

Between 10% and 20% of the estimated hundreds of millions of people infected worldwide with SARS-CoV-2 in the first 2 years went on to develop long-term symptoms. While many recover over time, doctors who have treated long COVID since 2020 said they see some patients still wrestling with the condition after 4 years.

The latest Centers for Disease Control and Prevention Household Pulse Survey, taken between March 5 and April 1, 2024, estimated that nearly 7% of the adult population — more than 18 million people — currently have long COVID. Data from other countries also suggest that millions have been living with long COVID for years now, and hundreds of thousands have seen their day-to-day activities significantly affected.

There is an urgent need for more funding, long COVID clinicians, multidisciplinary clinics, and education for non–long COVID physicians and specialists, doctors said. Instead, funding remains limited, clinics are closing, wait times are “horrendously long,” patients are left in limbo, and physicians are burning out.

“What’s changed in some ways is that there’s even less access to COVID rehab, which sounds crazy because there was very little to begin with,” said Alexandra Rendely, MD, a physical medicine and rehabilitation physician with the interdisciplinary Toronto Rehab, a part of the University Health Network of teaching hospitals in Toronto, Ontario, Canada.

“Patients are still being diagnosed every day, yet the resources available are becoming less and less.”

COVID-19 money earmarked during the pandemic was mostly limited to temporary emergency measures. As those funds dwindled, governments and institutions have decreased financial support. The Long COVID Moonshot campaign, organized by patients with long COVID, is pushing Congress to support $1 billion in annual research funding to close the financial chasm.
 

The Clinical Trial Conundrum

While long COVID clinics have come a long way in helping patients, gaps remain. Doctors may be unwilling to prescribe off-label treatments without proper clinical trials due to the potential risks and liabilities involved or due to the controversial or unconventional nature of the therapies, said Dr. Malcolm, who left his primary care practice more than 2 years ago to focus on long COVID.

In the absence of standard treatments, Dr. Malcolm and other doctors said they must take a trial-and-error approach in treating patients with long COVID that centers on addressing symptoms and not the underlying condition.

“There are actually a lot of treatments and a lot of them are not curative, but they can help people,” he said.

Dr. Malcolm, who is a medical director at Real Time Health Monitoring, a private clinic in the San Francisco Bay Area that specializes in long COVID and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), said it was important for him to be with a clinical team that understood and was supportive of his treatment decisions and was able to offer clinical support for those treatments if needed.

For physicians looking for clinical data before prescribing certain medications, the wait may be long. More than $1.5 billion in US federal funding has been earmarked to study long COVID, but the National Institutes of Health (NIH) has faced criticism from patients and scientists alike for its slow progress and emphasis on observational studies instead of research that could unravel the biological roots of long COVID. Among the clinical trials announced by the NIH’s RECOVER initiative, only a handful involve studying pharmaceutical treatments.

A 2023 editorial published in The Lancet called out the “dismal state of clinical research relative to the substantial burden of [long COVID]” and said, “we are clearly lacking tested pharmacological interventions that treat the underlying pathophysiology.” At the time of publication, it noted that of the 386 long COVID trials listed on ClinicalTrials.gov, only 12 were actually testing pharmacologic interventions.

There are also diagnostic and insurance barriers. The specialized tests that can detect long COVID anomalies are neither commonly known by primary care practitioners nor easily requested at the local lab, can be expensive, and are typically not covered by insurance, Dr. Malcolm explained.

Patients with long COVID also have the added barrier of being unable to advocate as easily because of their energy limitations, doctors said. Patients may appear outwardly fine, but fatigue and brain fog are among the many problems that cannot be measured in appearances. The condition has upended lives, some losing jobs, even homes, and the mental toll is why there is a “not insignificant” suicide rate.
 

One Patient’s 4-Year Journey

Charlie McCone, 34, used to be a tennis player and an active musician. But he’s spent the past 4 years mostly housebound, grappling with the aftermath of a SARS-CoV-2 infection he contracted in March 2020. He went from biking daily to work 10 miles and back to having at most 2 hours of energy per day.

In the first year alone, Mr. McCone saw more than two dozen doctors and specialists. The conditions now associated with long COVID, like ME/CFS, mast cell activation syndrome (a condition in which a patient experiences episodes of allergic symptoms such as hives, swelling, low blood pressure, and difficulty breathing), or dysautonomia (conditions that affect the autonomic nervous system, which controls automatic processes in the body) were not on physicians’ radars.

Then in 2021, he became bedbound for more than half a year after a Delta variant reinfection. He developed neurologic symptoms, including incapacitating fatigue, post-exertional malaise (where symptoms worsened after minimal physical or mental activity), left-sided weakness, and cognitive impairment. He stopped working altogether. But the worst was the shortness of breath he felt 24/7, even at rest. A battery of lab tests revealed nothing abnormal. He tried numerous drugs and the classic respiratory treatments.

Mr. McCone eventually connected with Dr. Malcolm over X and developed what he describes as an effective patient-doctor collaboration. When studies came out suggesting microclots were a common issue with patients with long COVID and positive outcomes were reported from anticoagulant therapy, they knew it could be one of the answers.

“After 3 weeks on [the antiplatelet drug], I was like, oh my god, my lungs are finally opening up,” said Mr. McCone. He has taken the medication for more than a year and a half, and some days he doesn’t even think about his respiratory symptoms.

“That trial-and-error process is just really long and hard and costly,” said Dr. Malcolm.

Today, fatigue and cognitive stamina are Mr. McCone’s main challenges, and he is far from recovered.

“[I had a] very fulfilling, happy life and now, it’s hard to think about. I’ve come a long way with my mental health and all this, but I’ve lost 4 years,” Mr. McCone said. “The prospect of me being here when I’m 40 seems very real ... so it’s pretty devastating.”
 

Lessons Learned, Hope Amid Ongoing Research

Despite the daunting obstacle, doctors said the science has come a long way for a new disease. We now know long COVID is likely caused by a combination of triggers, including viral reservoir in the tissue, inflammation, autoimmunity, and microclots; severity of infection is not necessarily an accurate risk factor predictor — long COVID can strike even those who had a mild infection; upward of 200 symptoms have been identified; and we know more about potential biomarkers that could lead to better diagnostic tools.

Unlike many other diseases and conditions with standard treatment protocols, long COVID treatments are typically aimed at addressing individual symptoms.

“It is very detailed and individualized to the patient’s specific symptoms and to the patient’s specific needs,” Dr. Rendely said. Symptoms can also fluctuate, relapse, or wax and wane, for example, so what ails a patient at their first doctor’s appointment could be completely different at the next appointment 2 months later.

Doctors are still hopeful the RECOVER research, which includes trials that look at autonomic and cognitive dysfunctions, will pave the way for more effective long COVID therapies. In Canada, Dr. Rendely is also eying the RECLAIM trial that is currently testing the effectiveness of pentoxifylline, which helps blood flow, and ibudilast, an anti-inflammatory drug.

Doctors are also hopeful when they see patients who have made “tremendous gains” or even full recoveries through their clinics. “It’s a new diagnosis, so I always tell my patients to think of this as a journey because I’m learning along with you,” said Jai Marathe, MD, an infectious disease physician at Boston Medical Center and an assistant professor of infectious diseases at Boston University Chobanian & Avedisian School of Medicine.

“Now we have 4 years of experience, but at the same time, no two long COVID patients are alike.”

Long COVID has also changed the way physicians view healthcare and how they practice medicine.

“I am a completely different person than I used to be because of this illness, and I don’t even have it. That is how profoundly it has affected how I view the universe,” said Dr. Malcolm. “I’ve been doing this for 4 years, and I’m very hopeful. But I don’t think about this in terms of months anymore. I think about this in terms of years.”

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

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

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

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

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

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

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

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

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

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

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

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

Too Many Barriers to Entry

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

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

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

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

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

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

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

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

Long Fight for Better Long COVID Research

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Too Many Barriers to Entry

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

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

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

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

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

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

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

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

Long Fight for Better Long COVID Research

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Too Many Barriers to Entry

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

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

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

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

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

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

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

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

Long Fight for Better Long COVID Research

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

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

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

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

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

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BERLIN — To date, mRNA vaccines have had their largest global presence in combating the COVID-19 pandemic. Intensive research is underway on many other potential applications for this vaccine technology, which suggests a promising future. Martina Prelog, MD, a pediatric and adolescent medicine specialist at the University Hospital of Würzburg in Germany, reported on the principles, research status, and perspectives for these vaccines at the 25th Travel and Health Forum of the Center for Travel Medicine in Berlin.

To understand the future, the immunologist first examined the past. “The induction of cellular and humoral immune responses by externally injected mRNA was discovered in the 1990s,” she said.
 

Instability Challenge

Significant hurdles in mRNA vaccinations included the instability of mRNA and the immune system’s ability to identify foreign mRNA as a threat and destroy mRNA fragments. “The breakthrough toward vaccination came through Dr. Katalin Karikó, who, along with Dr. Drew Weissman, both of the University of Pennsylvania School of Medicine, discovered in 2005 that modifications of mRNA (replacing the nucleoside uridine with pseudouridine) enable better stability of mRNA, reduced immunogenicity, and higher translational capacity at the ribosomes,” said Dr. Prelog.

With this discovery, the two researchers paved the way for the development of mRNA vaccines against COVID-19 and other diseases. They were awarded the Nobel Prize in medicine for their discovery last year.
 

Improved Scalability

“Since 2009, mRNA vaccines have been studied as a treatment option for cancer,” said Dr. Prelog. “Since 2012, they have been studied for the influenza virus and respiratory syncytial virus [RSV].” Consequently, several mRNA vaccines are currently in development or in approval studies. “The mRNA technology offers the advantage of quickly and flexibly responding to new variants of pathogens and the ability to scale up production when there is high demand for a particular vaccine.”

Different forms and designations of mRNA vaccines are used, depending on the application and desired effect, said Dr. Prelog.

In nucleoside-modified mRNA vaccines, modifications in the mRNA sequence enable the mRNA to remain in the body longer and to induce protein synthesis more effectively.

Lipid nanoparticle (LNP)–encapsulated mRNA vaccines protect the coding mRNA sequences against degradation by the body’s enzymes and facilitate the uptake of mRNA into cells, where it then triggers the production of the desired protein. In addition, LNPs are involved in cell stimulation and support the self-adjuvant effect of mRNA vaccines, thus eliminating the need for adjuvants.

Self-amplifying mRNA vaccines include a special mRNA that replicates itself in the cell and contains a sequence for RNA replicase, in addition to the coding sequence for the protein. This composition enables increased production of the target protein without the need for a high amount of external mRNA administration. Such vaccines could trigger a longer and stronger immune response because the immune system has more time to interact with the protein.
 

Cancer Immunotherapy

Dr. Prelog also discussed personalized vaccines for cancer immunotherapy. Personalized mRNA vaccines are tailored to the patient’s genetic characteristics and antigens. They could be used in cancer immunotherapy to activate the immune system selectively against tumor cells.

Multivalent mRNA vaccines contain mRNA that codes for multiple antigens rather than just one protein to generate an immune response. These vaccines could be particularly useful in fighting pathogens with variable or changing surface structures or in eliciting protection against multiple pathogens simultaneously.

The technology of mRNA-encoded antibodies involves introducing mRNA into the cell, which creates light and heavy chains of antibodies. This step leads to the formation of antibodies targeted against toxins (eg, diphtheria and tetanus), animal venoms, infectious agents, or tumor cells.
 

Genetic Engineering

Dr. Prelog also reviewed genetic engineering techniques. In regenerative therapy or protein replacement therapy, skin fibroblasts or other cells are transfected with mRNA to enable conversion into induced pluripotent stem cells. This approach avoids the risk for DNA integration into the genome and associated mutation risks.

Another approach is making post-transcriptional modifications through RNA interference. For example, RNA structures can be used to inhibit the translation of disease-causing proteins. This technique is currently being tested against HIV and tumors such as melanoma.

In addition, mRNA technologies can be combined with CRISPR/Cas9 technology (“gene scissors”) to influence the creation of gene products even more precisely. The advantage of this technique is that mRNA is only transiently expressed, thus preventing unwanted side effects. Furthermore, mRNA is translated directly in the cytoplasm, leading to a faster initiation of gene editing.

Of the numerous ongoing clinical mRNA vaccine studies, around 70% focus on infections, about 12% on cancer, and the rest on autoimmune diseases and neurodegenerative disorders, said Dr. Prelog.
 

Research in Infections

Research in the fields of infectious diseases and oncology is the most advanced: mRNA vaccines against influenza and RSV are already in advanced clinical trials, Dr. Prelog told this news organization.

“Conventional influenza vaccines contain immunogenic surface molecules against hemagglutinin and neuraminidase in various combinations of influenza strains A and B and are produced in egg or cell cultures,” she said. “This is a time-consuming manufacturing process that takes months and, particularly with the egg-based process, bears the risk of changing the vaccine strain.”

“Additionally, influenza viruses undergo antigenic shift and drift through recombination, thus requiring annual adjustments to the vaccines. Thus, these influenza vaccines often lose accuracy in targeting circulating seasonal influenza strains.”

Several mRNA vaccines being tested contain not only coding sequences against hemagglutinin and neuraminidase but also for structural proteins of influenza viruses. “These are more conserved and mutate less easily, meaning they could serve as the basis for universal pandemic influenza vaccines,” said Dr. Prelog.

An advantage of mRNA vaccines, she added, is the strong cellular immune response that they elicit. This response is intended to provide additional protection alongside specific antibodies. An mRNA vaccine with coding sequences for the pre-fusion protein of RSV is in phase 3 trials for approval for vaccination in patients aged 60 years and older. It shows high effectiveness even in older patients and those with comorbidities.
 

Elaborate Purification Process

Bacterial origin plasmid DNA is used to produce mRNA vaccines. The mRNA vaccines for COVID-19 raised concerns that production-related DNA residues could pose a safety risk and cause autoimmune diseases.

These vaccines “typically undergo a very elaborate purification process,” said Dr. Prelog. “This involves enzymatic digestion with DNase to fragment and deplete plasmid DNA, followed by purification using chromatography columns, so that no safety-relevant DNA fragments should remain afterward.”

Thus, the Paul-Ehrlich-Institut also pointed out the very small, fragmented plasmid DNA residues of bacterial origin in mRNA COVID-19 vaccines pose no risk, unlike residual DNA from animal cell culture might pose in other vaccines.
 

Prevention and Therapy

In addition to the numerous advantages of mRNA vaccines (such as rapid adaptability to new or mutated pathogens, scalability, rapid production capability, self-adjuvant effect, strong induction of cellular immune responses, and safety), there are also challenges in RNA technology as a preventive and therapeutic measure, according to Dr. Prelog.

“Stability and storability, as well as the costs of new vaccine developments, play a role, as do the long-term effects regarding the persistence of antibody and cellular responses,” she said. The COVID-19 mRNA vaccines, for example, showed a well-maintained cellular immune response despite a tendency toward a rapid decline in humoral immune response.

“The experience with COVID-19 mRNA vaccines and the new vaccine developments based on mRNA technology give hope for an efficient and safe preventive and therapeutic use, particularly in the fields of infectious diseases and oncology,” Dr. Prelog concluded.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

There is no association between the SARS-CoV-2 vaccine and the risk for new-onset seizure, data from a new meta-analysis of six randomized, placebo-controlled clinical trials (RCTs) showed.

Results of the pooled analysis that included 63,500 individuals vaccinated with SARS-CoV-2 and 55,000 who received a placebo vaccine showed there was no significant difference between the two groups with respect to new-onset seizures at 28- or 43-day follow-up.

Regarding new-onset seizures in the general population, there was no statistically significant difference in risk for seizure incidence among vaccinated individuals vs placebo recipients, according to our meta-analysis, wrote the investigators, led by Ali Rafati, MD, MPH, Iran University of Medical Sciences in Tehran.

The findings were published online in JAMA Neurology.

Mixed Results

Results from previous research have been mixed regarding the link between the SARS-CoV-2 vaccination and new-onset seizures, with some showing an association.

To learn more about the possible association between the vaccines and new-onset seizures, the researchers conducted a literature review and identified six RCTs that measured adverse events following SARS-CoV-2 vaccinations (including messenger RNA, viral vector, and inactivated virus) vs placebo or other vaccines.

While five of the studies defined new-onset seizures according to the Medical Dictionary for Regulatory Activities, trial investigators in the sixth RCT assessed and determined new-onset seizures in participants.

Participants received two vaccinations 28 days apart in five RCTs and only one vaccine in the sixth trial.

The research team searched the data for new-onset seizure in the 28 days following one or both COVID vaccinations.

No Link Found

After comparing the incidence of new-onset seizure between the 63,500 vaccine (nine new-onset seizures, 0.014%) and 55,000 placebo recipients (one new-onset seizure, 0.002%), investigators found no significant difference between the two groups (odds ratio [OR], 2.70; 95% CI, 0.76-9.57; P = .12)

Investigators also sliced the data several ways to see if it would yield different results. When they analyzed data by vaccine platform (viral vector) and age group (children), they didn’t observe significant differences in new-onset data.

The researchers also searched for data beyond the month following the injection to encompass the entire blinded phase, so they analyzed the results of three RCTs that reported adverse events up to 162 days after the vaccine.

After pooling the results from the three studies, investigators found no statistical difference between the vaccine and placebo groups in terms of the new-onset seizure (OR, 2.31; 95% CI, 0.86%-3.23; P > .99)

Study limitations included the missing information on vaccine doses or risk factors for the development of seizures. Also, the RCTs included in the meta-analysis were conducted at different times, so the SARS-CoV-2 vaccines may have differed in their composition and efficacy.

“The global vaccination drive against SARS-CoV-2 has been a monumental effort in combating the pandemic. SARS-CoV-2 vaccinations that are now available appear safe and appropriate,” the authors wrote.

There were no study funding sources or disclosures reported.

A version of this article appeared on Medscape.com.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.

Dhaval Desai, MD, was teaching his 4-year-old to ride a bike after another exhausting shift at the hospital during the summer after the first COVID-19 surge. He was putting on a happy face and forcing out a “Yay!” he did not feel. The pandemic had taken its toll, and he just wanted to lie down and be alone. Realizing that he was “scraping to find joy” was when he knew something was wrong.

“I was giving, giving, giving at work a lot, and I had little left to give at home,” said Dr. Desai, director of hospital medicine at Emory Saint Joseph’s Hospital and an assistant professor of medicine at Emory University in Atlanta, Georgia.

At work, he worried about his wife managing two kids — including a newborn — during the pandemic. At home, he stressed about work and the crush of patients with COVID the hospital was grappling to handle. He was exhausted, resentful, and angry, and it was jeopardizing what mattered most to him: His home life.

“It was all colliding…I realized, OK, I’m struggling,” he said.

Dr. Desai is one of thousands of physicians across the United States who have experienced burnout and depression, exacerbated by the pandemic. After 4 years, the impact is still being felt. Medscape’s 2024 annual report on this issue found that burnout and depression among doctors — while encouragingly better than the prior year — remain higher than before COVID. For doctors caring for patients with long COVID, those suffering from the debilitating aftereffects of an infection, the sense of helplessness when recovery is elusive can also weigh heavily.

Overall, more female physicians reported feeling burned out and depressed. Experts attributed this gap to issues including fewer women in supportive leadership and mentoring roles, compensation disparities, fewer career advancement opportunities, and more responsibilities caring for children and elders.

Multiple international studies and reports have highlighted the surge in burnout experienced by physicians and healthcare workers globally during the pandemic. Even before COVID, studies found the suicide rate among male and female US physicians was higher than the general population and higher than any other profession, including the military. The risk among female physicians, in particular, was 250%-400% higher.

“That’s really, on average, one a day, and that’s really unacceptable. No one should die by suicide, but a physician who knows the risks and knows that, should never do that,” said Dr. Desai about suicides overall among doctors.

The story of Lorna Breen had rattled Dr. Desai. Dr. Breen was a Manhattan physician who died by suicide in April 2020 after grappling with the city’s devastating first wave and then contracting COVID-19 herself. While Dr. Desai did not have thoughts of suicide, he was facing his own battles. Those experiences and the stigma around mental health prompted him to write his book, Burning Out on the Covid Front Lines: A Doctor’s Memoir of Fatherhood, Race and Perseverance in the Pandemic, with the hope that it can help others like him.
 

Mental Health Stigma

But despite the body of research and growing awareness toward addressing mental health among physicians, almost four in 10 doctors are wary of revealing their personal struggles.

More than half of those surveyed in the Medscape Medical News report said they had not consulted a mental health professional before and would not do so going forward either. The fear of tarnishing their reputation or even losing their license keeps doctors silent. Advocates and groups like the Dr. Lorna Breen Heroes’ Foundation are pushing for hospitals and healthcare systems to remove and rephrase invasive and stigmatizing language around mental health in licensure, credentialing, or insurance applications.
 

Burnout Triggers: Systemic Problems, Social Tensions

Burnout can make a person feel “depleted and used up” and is characterized by extreme tiredness, low energy, frustration about work, emotional distance or numbness, and difficulty with concentration, responsibilities, or creativity. It can make an individual feel helpless, alone, defeated, cynical, and without purpose and can also cause physical symptoms such as headaches, loss of appetite, insomnia, and body aches. Unaddressed, it can lead to depression, anxiety, and a variety of physical health issues.

“We can still be highly functional and not okay,” said Dr. Desai.

For doctors, burnout often builds over time from large and small systemic problems and inefficiencies, multiplied by a dozen or more patients each day: Not enough time for documentation, complicated paperwork, navigating byzantine health and insurance systems, and hitting roadblocks. The administrative work, combined with an enormous patient load, and staffing and resource shortages create barriers to care and cuts into the amount of time they can spend providing actual care.

These existing problems worsened as patients with COVID overwhelmed hospitals and clinics. At the same time, healthcare workers worried about caring for the sick, getting infected themselves, or having multiple staff falling ill at once. As each surge came and went, backlash, hostility, abuse, and even violence toward healthcare workers also increased. The discrimination some medical staff were subjected to compounded the burnout.

“When we’re not getting the support we need as physicians and healthcare workers, that adds to burnout, and I saw that in my colleagues,” said Dr. Desai.
 

Impact of Burnout

At the Mount Sinai Center for Post-COVID Care in New York City, doctors grapple with feelings of helplessness in caring for patients with long COVID who show little sign of recovery. That emotional toll can also be difficult, said director Zijian Chen, MD, who helped launch the clinic in May 2020.

“Sometimes you’re faced with patients who you’re trying to do everything for, but they’re not just not getting better,” said Dr. Chen. “It’s really frustrating because we want everybody to get better. So, there’s that lack of fulfillment there that can cause a sense of burnout.”

While the worst outcomes and death rates initially brought on by acute infections have lessened, long COVID clinics exemplify some of the ongoing challenges within healthcare. Many operate with insufficient financial and staffing resources despite wait-lists and a steady flow of new and returning patients. Even with the demand, a number of these clinics have shuttered, leaving patients without access to much-needed medical help.

“There are clinicians who are burning out. That is definitely something that I’ve seen,” said Monica Verduzco-Gutierrez, MD, a professor and chair of the Department of Rehabilitation Medicine at the University of Texas Health Science Center in San Antonio, Texas.

“[It] takes a lot of resources for a successful long COVID clinic. A lot of special funding may be drying up and couple that with clinicians burning out, then they’re going to shut their doors.”

And it’s not just long COVID clinics. Data have shown an overall exodus in healthcare, especially during the pandemic. One study found burnout was one of the “most impactful” predictors of a physician’s intention to leave the profession during the pandemic. The loss of talent and skills during a major health crisis can put the entire system under stress, with patients ultimately suffering from poorer care.

“Healthcare system fragility and the chaos is far worse than it was before. We are continuing to be forced to do more with less,” said Dr. Desai.
 

Alleviating Burnout

While it is difficult to assess whether burnout from the pandemic is transient, experts say this is an opportunity for health institutions to learn from these experiences and implement policies and actions that can help reduce the mental health strain on staff. One study found that changes made by organizations had a bigger positive impact on reducing burnout than individual changes.

Advocates say more support staff, more work flexibility, and higher compensation would significantly ease the burden that drives burnout and depression.

In addition, half the physicians surveyed in the Medscape Medical News report felt their employers were not acknowledging how pervasive burnout is at their workplace. Having a trusted peer or leader set an example by sharing his or her own challenging experiences and saying it›s time to address these struggles can be an enormously validating step forward, said Dr. Desai. Acknowledging his own difficulties was not only a huge weight off his shoulders but also helped surpris colleagues who sought him out for counsel.

“I’m not suggesting everybody get on medication,” he said. “But talking to a therapist, acknowledging there’s issues, restructuring your life to realize something’s off, and just knowing that you’re not alone? That’s huge.”

Dr. Desai said he still faces personal challenges but is in a much better place, doing well at work and at home. He talks to a therapist, is taking medication, and has developed better coping mechanisms. He is spending more time with his family, detaching for a few hours from work-related emails, learning to draw boundaries and say no, and trying to be more present and “intentional” in connecting with colleagues and patients.

“It’s okay to not be okay,” said Dr. Desai. “It’s okay to be vulnerable and acknowledge when we can’t do more.”

Are you in a crisis? Call or text 988 or text TALK to 741741. For immediate support for healthcare professionals, as well as resources for institutions and organizations, visit: afsp.org/suicide-prevention-for-healthcare-professionals/#facts-about-mental-health-and-suicide.

A version of this article appeared on Medscape.com.

Paxlovid does not significantly alleviate symptoms of COVID-19 compared with placebo among nonhospitalized adults, a new study published April 3 in The New England Journal of Medicine found. 

The results suggest that the drug, a combination of nirmatrelvir and ritonavir, may not be particularly helpful for patients who are not at high risk for severe COVID-19. However, although the rate of hospitalization and death from any cause was low overall, the group that received Paxlovid had a reduced rate compared with people in the placebo group, according to the researchers. 

“Clearly, the benefit observed among unvaccinated high-risk persons does not extend to those at lower risk for severe COVID-19,” Rajesh T. Gandhi, MD, and Martin Hirsch, MD, of Massachusetts General Hospital in Boston, wrote in an editorial accompanying the journal article. “This result supports guidelines that recommend nirmatrelvir–ritonavir only for persons who are at high risk for disease progression.”

The time from onset to relief of COVID-19 symptoms — including cough, shortness of breath, body aches, and chills — did not differ significantly between the two study groups, the researchers reported. The median time to sustained alleviation of symptoms was 12 days for the Paxlovid group compared with 13 days in the placebo group (P = .60).

However, the phase 2/3 trial found a 57.6% relative reduction in the risk for hospitalizations or death among people who took Paxlovid and were vaccinated but were at high risk for poor outcomes, according to Jennifer Hammond, PhD, head of antiviral development for Pfizer, which makes the drug, and the corresponding author on the study.

Paxlovid has “an increasing body of evidence supporting the strong clinical value of the treatment in preventing hospitalization and death among eligible patients across age groups, vaccination status, and predominant variants,” Dr. Hammond said. 

She and her colleagues analyzed data from 1250 adults with symptomatic COVID-19. Participants were fully vaccinated and had a high risk for progression to severe disease or were never vaccinated or had not been in the previous year and had no risk factors for progression to severe disease.

More than half of participants were women, 78.5% were White and 41.4% identified as Hispanic or Latinx. Almost three quarters underwent randomization within 3 days of the start of symptoms, and a little over half had previously received a COVID-19 vaccination. Almost half had one risk factor for severe illness, the most common of these being hypertension (12.3%). 

In a subgroup analysis of high-risk participants, hospitalization or death occurred in 0.9% of patients in the Paxlovid group and 2.2% in the placebo group (95% CI, -3.3 to 0.7). 

The study’s limitations include that the statistical analysis of COVID-19–related hospitalizations or death from any cause was only descriptive, “because the results for the primary efficacy end point were not significant,” the authors wrote. 

Participants who were vaccinated and at high risk were also enrolled regardless of when they had last had a vaccine dose. Furthermore, Paxlovid has a telltale taste, which may have affected the blinding. Finally, the trial was started when the B.1.617.2 (Delta) variant was predominant.

Dr. Gandhi and Dr. Hirsch pointed out that only 5% of participants in the trial were older than 65 years and that other than risk factors such as obesity and smoking, just 2% of people had heart or lung disease. 

“As with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir–ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit,” Dr. Gandhi and Dr. Hirsch wrote in the editorial. “Thus, it appears reasonable to recommend nirmatrelvir–ritonavir primarily for the treatment of COVID-19 in older patients (particularly those ≥ 65 years of age), those who are immunocompromised, and those who have conditions that substantially increase the risk of severe COVID-19, regardless of previous vaccination or infection status.”

The study was supported by Pfizer. 

A version of this article appeared on Medscape.com .

Paxlovid does not significantly alleviate symptoms of COVID-19 compared with placebo among nonhospitalized adults, a new study published April 3 in The New England Journal of Medicine found. 

The results suggest that the drug, a combination of nirmatrelvir and ritonavir, may not be particularly helpful for patients who are not at high risk for severe COVID-19. However, although the rate of hospitalization and death from any cause was low overall, the group that received Paxlovid had a reduced rate compared with people in the placebo group, according to the researchers. 

“Clearly, the benefit observed among unvaccinated high-risk persons does not extend to those at lower risk for severe COVID-19,” Rajesh T. Gandhi, MD, and Martin Hirsch, MD, of Massachusetts General Hospital in Boston, wrote in an editorial accompanying the journal article. “This result supports guidelines that recommend nirmatrelvir–ritonavir only for persons who are at high risk for disease progression.”

The time from onset to relief of COVID-19 symptoms — including cough, shortness of breath, body aches, and chills — did not differ significantly between the two study groups, the researchers reported. The median time to sustained alleviation of symptoms was 12 days for the Paxlovid group compared with 13 days in the placebo group (P = .60).

However, the phase 2/3 trial found a 57.6% relative reduction in the risk for hospitalizations or death among people who took Paxlovid and were vaccinated but were at high risk for poor outcomes, according to Jennifer Hammond, PhD, head of antiviral development for Pfizer, which makes the drug, and the corresponding author on the study.

Paxlovid has “an increasing body of evidence supporting the strong clinical value of the treatment in preventing hospitalization and death among eligible patients across age groups, vaccination status, and predominant variants,” Dr. Hammond said. 

She and her colleagues analyzed data from 1250 adults with symptomatic COVID-19. Participants were fully vaccinated and had a high risk for progression to severe disease or were never vaccinated or had not been in the previous year and had no risk factors for progression to severe disease.

More than half of participants were women, 78.5% were White and 41.4% identified as Hispanic or Latinx. Almost three quarters underwent randomization within 3 days of the start of symptoms, and a little over half had previously received a COVID-19 vaccination. Almost half had one risk factor for severe illness, the most common of these being hypertension (12.3%). 

In a subgroup analysis of high-risk participants, hospitalization or death occurred in 0.9% of patients in the Paxlovid group and 2.2% in the placebo group (95% CI, -3.3 to 0.7). 

The study’s limitations include that the statistical analysis of COVID-19–related hospitalizations or death from any cause was only descriptive, “because the results for the primary efficacy end point were not significant,” the authors wrote. 

Participants who were vaccinated and at high risk were also enrolled regardless of when they had last had a vaccine dose. Furthermore, Paxlovid has a telltale taste, which may have affected the blinding. Finally, the trial was started when the B.1.617.2 (Delta) variant was predominant.

Dr. Gandhi and Dr. Hirsch pointed out that only 5% of participants in the trial were older than 65 years and that other than risk factors such as obesity and smoking, just 2% of people had heart or lung disease. 

“As with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir–ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit,” Dr. Gandhi and Dr. Hirsch wrote in the editorial. “Thus, it appears reasonable to recommend nirmatrelvir–ritonavir primarily for the treatment of COVID-19 in older patients (particularly those ≥ 65 years of age), those who are immunocompromised, and those who have conditions that substantially increase the risk of severe COVID-19, regardless of previous vaccination or infection status.”

The study was supported by Pfizer. 

A version of this article appeared on Medscape.com .

Paxlovid does not significantly alleviate symptoms of COVID-19 compared with placebo among nonhospitalized adults, a new study published April 3 in The New England Journal of Medicine found. 

The results suggest that the drug, a combination of nirmatrelvir and ritonavir, may not be particularly helpful for patients who are not at high risk for severe COVID-19. However, although the rate of hospitalization and death from any cause was low overall, the group that received Paxlovid had a reduced rate compared with people in the placebo group, according to the researchers. 

“Clearly, the benefit observed among unvaccinated high-risk persons does not extend to those at lower risk for severe COVID-19,” Rajesh T. Gandhi, MD, and Martin Hirsch, MD, of Massachusetts General Hospital in Boston, wrote in an editorial accompanying the journal article. “This result supports guidelines that recommend nirmatrelvir–ritonavir only for persons who are at high risk for disease progression.”

The time from onset to relief of COVID-19 symptoms — including cough, shortness of breath, body aches, and chills — did not differ significantly between the two study groups, the researchers reported. The median time to sustained alleviation of symptoms was 12 days for the Paxlovid group compared with 13 days in the placebo group (P = .60).

However, the phase 2/3 trial found a 57.6% relative reduction in the risk for hospitalizations or death among people who took Paxlovid and were vaccinated but were at high risk for poor outcomes, according to Jennifer Hammond, PhD, head of antiviral development for Pfizer, which makes the drug, and the corresponding author on the study.

Paxlovid has “an increasing body of evidence supporting the strong clinical value of the treatment in preventing hospitalization and death among eligible patients across age groups, vaccination status, and predominant variants,” Dr. Hammond said. 

She and her colleagues analyzed data from 1250 adults with symptomatic COVID-19. Participants were fully vaccinated and had a high risk for progression to severe disease or were never vaccinated or had not been in the previous year and had no risk factors for progression to severe disease.

More than half of participants were women, 78.5% were White and 41.4% identified as Hispanic or Latinx. Almost three quarters underwent randomization within 3 days of the start of symptoms, and a little over half had previously received a COVID-19 vaccination. Almost half had one risk factor for severe illness, the most common of these being hypertension (12.3%). 

In a subgroup analysis of high-risk participants, hospitalization or death occurred in 0.9% of patients in the Paxlovid group and 2.2% in the placebo group (95% CI, -3.3 to 0.7). 

The study’s limitations include that the statistical analysis of COVID-19–related hospitalizations or death from any cause was only descriptive, “because the results for the primary efficacy end point were not significant,” the authors wrote. 

Participants who were vaccinated and at high risk were also enrolled regardless of when they had last had a vaccine dose. Furthermore, Paxlovid has a telltale taste, which may have affected the blinding. Finally, the trial was started when the B.1.617.2 (Delta) variant was predominant.

Dr. Gandhi and Dr. Hirsch pointed out that only 5% of participants in the trial were older than 65 years and that other than risk factors such as obesity and smoking, just 2% of people had heart or lung disease. 

“As with many medical interventions, there is likely to be a gradient of benefit for nirmatrelvir–ritonavir, with the patients at highest risk for progression most likely to derive the greatest benefit,” Dr. Gandhi and Dr. Hirsch wrote in the editorial. “Thus, it appears reasonable to recommend nirmatrelvir–ritonavir primarily for the treatment of COVID-19 in older patients (particularly those ≥ 65 years of age), those who are immunocompromised, and those who have conditions that substantially increase the risk of severe COVID-19, regardless of previous vaccination or infection status.”

The study was supported by Pfizer. 

A version of this article appeared on Medscape.com .

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE: 

There were few cases of SARS-CoV-2 infections among emergency department (ED) healthcare personnel and no substantial changes in the delivery of emergency medical care during the initial phase of the COVID-19 pandemic.

METHODOLOGY:

• This multicenter prospective cohort study of US ED healthcare personnel called Project COVERED was conducted from May to December 2020 to evaluate the following outcomes:
• The possibility of infected ED personnel reporting to work
• The burden of COVID-19 symptoms on an ED personnel’s work status
• The association between SARS-CoV-2 infection levels and ED staffing
• Project COVERED enrolled 1673 ED healthcare personnel with 29,825 person weeks of observational data from 25 geographically diverse EDs.
• The presence of any SARS-CoV-2 infection was determined using reverse transcription polymerase chain reaction or IgG antibody testing at baseline, week 2, week 4, and every four subsequent weeks through week 20.
• Investigators also collected weekly data on ED staffing and the incidence of SARS-CoV-2 infections in healthcare facilities.

TAKEAWAY:

• Despite the absence of widespread natural immunity or COVID-19 vaccine availability during the time of this study, only 4.5% of ED healthcare personnel tested positive for SARS-CoV-2 infections, with more than half (57.3%) not experiencing any symptoms.
• Most personnel (83%) who experienced symptoms associated with COVID-19 reported working at least one shift in the ED and nearly all of them continued to work until they received laboratory confirmation of their infection.
• The working time lost as a result of COVID-19 and related concerns was minimal, as 89 healthcare personnel reported 90 person weeks of missed work (0.3% of all weeks).
• During this study, physician-staffing levels ranged from 98.7% to 102.0% of normal staffing, with similar values noted for nursing and nonclinical staffs. Reduced staffing was rare, even during COVID-19 surges.

IN PRACTICE:

“Our findings suggest that the cumulative interaction between infected healthcare personnel and others resulted in a negligible risk of transmission on the scale of public health emergencies,” the authors wrote.

SOURCE:

This study was led by Kurt D. Weber, MD, Department of Emergency Medicine, Orlando Health, Orlando, Florida, and published online in Annals of Emergency Medicine.

LIMITATIONS:

Data regarding the Delta variant surges that occurred toward the end of December and the ED status after the advent of the COVID-19 vaccine were not recorded. There may also have been a selection bias risk in this study because the volunteer participants may have exhibited behaviors like social distancing and use of protective equipment, which may have decreased their risk for infections.

DISCLOSURES:

This study was funded by a cooperative agreement from the Centers for Disease Control and Prevention and the Institute for Clinical and Translational Science at the University of Iowa through a grant from the National Center for Advancing Translational Sciences at the National Institutes of Health. The authors declared no conflicts of interest.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Receipt of the bivalent COVID-19 vaccine was not associated with an increased stroke risk in the first 6 weeks after vaccination with either the Pfizer or Moderna vaccines, a new study of Medicare beneficiaries showed.

METHODOLOGY:

• The analysis included 5.4 million people age ≥ 65 years who received either the Pfizer-BioNTech COVID-19 bivalent vaccine or the Moderna bivalent vaccine, or the Pfizer vaccine and a high-dose or adjuvanted concomitant influenza vaccine (ie, administered on the same day).
• A total of 11,001 of the cohort experienced a stroke in the first 90 days after vaccination.
• The main outcome was stroke risk (nonhemorrhagic stroke, transient ischemic attack [TIA], or hemorrhagic stroke) during the 1- to 21-day or 22- to 42-day window after vaccination vs the 43- to 90-day control window.
• The mean age of participants was 74 years, and 56% were female.

TAKEAWAY:

• There was no statistically significant association with either brand of the COVID-19 bivalent vaccine or any of the stroke outcomes during the 1- to 21-day or 22- to 42-day risk window compared with the 43- to 90-day control window (incidence rate ratio [IRR] range, 0.72-1.12).
• Vaccination with COVID-19 bivalent vaccine plus a high-dose or adjuvanted influenza vaccine (n = 4596) was associated with a significantly greater risk for nonhemorrhagic stroke 22-42 days after vaccination with Pfizer-BioNTech (IRR, 1.20; risk difference/100,000 doses, 3.13) and an increase in TIA risk 1-21 days after vaccination with Moderna (IRR, 1.35; risk difference/100,000 doses, 3.33).
• There was a significant association between vaccination with a high-dose or adjuvanted influenza vaccine (n = 21,345) and nonhemorrhagic stroke 22-42 days after vaccination (IRR, 1.09; risk difference/100,000 doses, 1.65).

IN PRACTICE:

“The clinical significance of the risk of stroke after vaccination must be carefully considered together with the significant benefits of receiving an influenza vaccination,” the authors wrote. “Because the framework of the current self-controlled case series study does not compare the populations who were vaccinated vs those who were unvaccinated, it does not account for the reduced rate of severe influenza after vaccination. More studies are needed to better understand the association between high-dose or adjuvanted influenza vaccination and stroke.”

SOURCE:

Yun Lu, PhD, of the Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, was the lead and corresponding author of the study. It was published online on March 19 in JAMA.

LIMITATIONS:

Some stroke cases may have been missed or misclassified. The study included only vaccinated individuals — a population considered to have health-seeking behaviors — which may limit the generalizability of the findings. The study was conducted using COVID-19 bivalent vaccines, which are no longer available.

DISCLOSURES:

This work was funded by the US Food and Drug Administration through an interagency agreement with the Centers for Medicare & Medicaid Services. Dr. Lu reported no relevant financial relationships. The other authors’ disclosures are listed in the original paper.

A version of this article appeared on Medscape.com.

TOPLINE:

Hospitalization for influenza is linked to a greater risk for subsequent neurologic disorders including migraine, stroke, or epilepsy than is hospitalization for COVID-19, results of a large study show.

METHODOLOGY:

• Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
• In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
• Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
• If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.

TAKEAWAY:

• Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
• After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
• In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.

IN PRACTICE:

“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.

SOURCE:

Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.

LIMITATIONS:

The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.

DISCLOSURES:

The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Hospitalization for influenza is linked to a greater risk for subsequent neurologic disorders including migraine, stroke, or epilepsy than is hospitalization for COVID-19, results of a large study show.

METHODOLOGY:

• Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
• In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
• Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
• If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.

TAKEAWAY:

• Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
• After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
• In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.

IN PRACTICE:

“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.

SOURCE:

Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.

LIMITATIONS:

The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.

DISCLOSURES:

The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Hospitalization for influenza is linked to a greater risk for subsequent neurologic disorders including migraine, stroke, or epilepsy than is hospitalization for COVID-19, results of a large study show.

METHODOLOGY:

• Researchers used healthcare claims data to compare 77,300 people hospitalized with COVID-19 with 77,300 hospitalized with influenza. The study did not include individuals with long COVID.
• In the final sample of 154,500 participants, the mean age was 51 years, and more than half (58%) were female.
• Investigators followed participants from both cohorts for a year to find out how many of them had medical care for six of the most common neurologic disorders: migraine, epilepsy, stroke, neuropathy, movement disorders, and dementia.
• If participants had one of these neurologic disorders prior to the original hospitalization, the primary outcome involved subsequent healthcare encounters for the neurologic diagnosis.

TAKEAWAY:

• Participants hospitalized with COVID-19 versus influenza were significantly less likely to require care in the following year for migraine (2% vs 3.2%), epilepsy (1.6% vs 2.1%), neuropathy (1.9% vs 3.6%), movement disorders (1.5% vs 2.5%), stroke (2% vs 2.4%), and dementia (2% vs 2.3%) (all P < .001).
• After adjusting for age, sex, and other health conditions, researchers found that people hospitalized with COVID-19 had a 35% lower risk of receiving care for migraine, a 22% lower risk of receiving care for epilepsy, and a 44% lower risk of receiving care for neuropathy than those with influenza. They also had a 36% lower risk of receiving care for movement disorders, a 10% lower risk for stroke (all P < .001), as well as a 7% lower risk for dementia (P = .0007).
• In participants who did not have a preexisting neurologic condition at the time of hospitalization for either COVID-19 or influenza, 2.8% hospitalized with COVID-19 developed one in the next year compared with 5% of those hospitalized with influenza.

IN PRACTICE:

“While the results were not what we expected to find, they are reassuring in that we found being hospitalized with COVID did not lead to more care for common neurologic conditions when compared to being hospitalized with influenza,” study investigator Brian C. Callaghan, MD, of University of Michigan, Ann Arbor, said in a press release.

SOURCE:

Adam de Havenon, MD, of Yale University in New Haven, Connecticut, led the study, which was published online on March 20 in Neurology.

LIMITATIONS:

The study relied on ICD codes in health claims databases, which could introduce misclassification bias. Also, by selecting only individuals who had associated hospital-based care, there may have been a selection bias based on disease severity.

DISCLOSURES:

The study was funded by the American Academy of Neurology. Dr. De Havenon reported receiving consultant fees from Integra and Novo Nordisk and royalty fees from UpToDate and has equity in Titin KM and Certus. Dr. Callaghan has consulted for DynaMed and the Vaccine Injury Compensation Program. Other disclosures were noted in the original article.
 

A version of this article appeared on Medscape.com.