Covid ICYMI

TOPLINE:

The COVID-19 booster was linked to shorter menstrual cycles in adolescent girls in the 4 months following administration, particularly when teens were in their follicular phase. The vaccine did not appear to be associated with shifts in menstrual flow, pain, or other symptoms.
 

METHODOLOGY:

• Reports of menstrual cycle changes following the COVID-19 vaccination began to emerge in early 2021, raising concerns about the impact of the vaccine on menstrual health.
• Researchers conducted a prospective study including 65 adolescent girls (mean age, 17.3 years), of whom 47 had received an initial series of COVID-19 vaccination at least 6 months prior to receiving a booster dose (booster group), and 18 had not received the booster vaccine (control group), two of whom had never received any COVID-19 vaccine, four who had received an initial vaccine but not a booster, and 12 who had received an initial vaccine and booster but more than 6 months prior to the study.
• Menstrual cycle length was measured for three cycles prior to and four cycles after vaccination in the booster group and for seven cycles in the control group.
• Menstrual flow, pain, and stress were measured at baseline and monthly for 3 months post vaccination.

TAKEAWAY:

• Participants in the booster group experienced shorter cycles by an average of 5.35 days after receiving the COVID-19 booster vaccine (P = .03), particularly during the second cycle. In contrast, those in the control group did not experience any changes in the menstrual cycle length.
• Receiving the booster dose in the follicular phase was associated with significantly shorter menstrual cycles, compared with pre-booster cycles (P = .0157).
• Menstrual flow, pain, and other symptoms remained unaffected after the COVID-19 booster vaccination.
• Higher stress levels at baseline were also associated with a shorter length of the menstrual cycle (P = .03) in both groups, regardless of the booster vaccination status.

IN PRACTICE:

“These data are potentially important for counseling parents regarding potential vaccine refusal in the future for their teen daughters,” the authors wrote.

SOURCE:

This study was led by Laura A. Payne, PhD, from McLean Hospital in Boston, and was published online in the Journal of Adolescent Health.

LIMITATIONS:

The sample size for the booster and control groups was relatively small and homogeneous. The study did not include the height, weight, birth control use, or other chronic conditions of the participants, which may have influenced the functioning of the menstrual cycle. The control group included a majority of teens who had previously received a vaccine and even a booster, which could have affected results.

DISCLOSURES:

This study was supported by grants from the Eunice Kennedy Shriver National Institute for Child Health and Human Development. Some authors received consulting fees, travel reimbursements, honoraria, research funding, and royalties from Bayer Healthcare, Mahana Therapeutics, Gates, and Merck, among others.

This article was created 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.

TOPLINE:

The COVID-19 booster was linked to shorter menstrual cycles in adolescent girls in the 4 months following administration, particularly when teens were in their follicular phase. The vaccine did not appear to be associated with shifts in menstrual flow, pain, or other symptoms.
 

METHODOLOGY:

• Reports of menstrual cycle changes following the COVID-19 vaccination began to emerge in early 2021, raising concerns about the impact of the vaccine on menstrual health.
• Researchers conducted a prospective study including 65 adolescent girls (mean age, 17.3 years), of whom 47 had received an initial series of COVID-19 vaccination at least 6 months prior to receiving a booster dose (booster group), and 18 had not received the booster vaccine (control group), two of whom had never received any COVID-19 vaccine, four who had received an initial vaccine but not a booster, and 12 who had received an initial vaccine and booster but more than 6 months prior to the study.
• Menstrual cycle length was measured for three cycles prior to and four cycles after vaccination in the booster group and for seven cycles in the control group.
• Menstrual flow, pain, and stress were measured at baseline and monthly for 3 months post vaccination.

TAKEAWAY:

• Participants in the booster group experienced shorter cycles by an average of 5.35 days after receiving the COVID-19 booster vaccine (P = .03), particularly during the second cycle. In contrast, those in the control group did not experience any changes in the menstrual cycle length.
• Receiving the booster dose in the follicular phase was associated with significantly shorter menstrual cycles, compared with pre-booster cycles (P = .0157).
• Menstrual flow, pain, and other symptoms remained unaffected after the COVID-19 booster vaccination.
• Higher stress levels at baseline were also associated with a shorter length of the menstrual cycle (P = .03) in both groups, regardless of the booster vaccination status.

IN PRACTICE:

“These data are potentially important for counseling parents regarding potential vaccine refusal in the future for their teen daughters,” the authors wrote.

SOURCE:

This study was led by Laura A. Payne, PhD, from McLean Hospital in Boston, and was published online in the Journal of Adolescent Health.

LIMITATIONS:

The sample size for the booster and control groups was relatively small and homogeneous. The study did not include the height, weight, birth control use, or other chronic conditions of the participants, which may have influenced the functioning of the menstrual cycle. The control group included a majority of teens who had previously received a vaccine and even a booster, which could have affected results.

DISCLOSURES:

This study was supported by grants from the Eunice Kennedy Shriver National Institute for Child Health and Human Development. Some authors received consulting fees, travel reimbursements, honoraria, research funding, and royalties from Bayer Healthcare, Mahana Therapeutics, Gates, and Merck, among others.

This article was created 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.

TOPLINE:

The COVID-19 booster was linked to shorter menstrual cycles in adolescent girls in the 4 months following administration, particularly when teens were in their follicular phase. The vaccine did not appear to be associated with shifts in menstrual flow, pain, or other symptoms.
 

METHODOLOGY:

• Reports of menstrual cycle changes following the COVID-19 vaccination began to emerge in early 2021, raising concerns about the impact of the vaccine on menstrual health.
• Researchers conducted a prospective study including 65 adolescent girls (mean age, 17.3 years), of whom 47 had received an initial series of COVID-19 vaccination at least 6 months prior to receiving a booster dose (booster group), and 18 had not received the booster vaccine (control group), two of whom had never received any COVID-19 vaccine, four who had received an initial vaccine but not a booster, and 12 who had received an initial vaccine and booster but more than 6 months prior to the study.
• Menstrual cycle length was measured for three cycles prior to and four cycles after vaccination in the booster group and for seven cycles in the control group.
• Menstrual flow, pain, and stress were measured at baseline and monthly for 3 months post vaccination.

TAKEAWAY:

• Participants in the booster group experienced shorter cycles by an average of 5.35 days after receiving the COVID-19 booster vaccine (P = .03), particularly during the second cycle. In contrast, those in the control group did not experience any changes in the menstrual cycle length.
• Receiving the booster dose in the follicular phase was associated with significantly shorter menstrual cycles, compared with pre-booster cycles (P = .0157).
• Menstrual flow, pain, and other symptoms remained unaffected after the COVID-19 booster vaccination.
• Higher stress levels at baseline were also associated with a shorter length of the menstrual cycle (P = .03) in both groups, regardless of the booster vaccination status.

IN PRACTICE:

“These data are potentially important for counseling parents regarding potential vaccine refusal in the future for their teen daughters,” the authors wrote.

SOURCE:

This study was led by Laura A. Payne, PhD, from McLean Hospital in Boston, and was published online in the Journal of Adolescent Health.

LIMITATIONS:

The sample size for the booster and control groups was relatively small and homogeneous. The study did not include the height, weight, birth control use, or other chronic conditions of the participants, which may have influenced the functioning of the menstrual cycle. The control group included a majority of teens who had previously received a vaccine and even a booster, which could have affected results.

DISCLOSURES:

This study was supported by grants from the Eunice Kennedy Shriver National Institute for Child Health and Human Development. Some authors received consulting fees, travel reimbursements, honoraria, research funding, and royalties from Bayer Healthcare, Mahana Therapeutics, Gates, and Merck, among others.

This article was created 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.

We are quickly approaching the typical cold and flu season. But can we call anything typical since 2020? Since 2020, there have been different recommendations for prevention, testing, return to work, and treatment since our world was rocked by the pandemic. Now that we are in the “post-pandemic” era, family physicians and other primary care professionals are the front line for discussions on prevention, evaluation, and treatment of the typical upper-respiratory infections, influenza, and COVID-19.

Let’s start with prevention. We have all heard the old adage, an ounce of prevention is worth a pound of cure. In primary care, we need to focus on prevention. Vaccination is often one of our best tools against the myriad of infections we are hoping to help patients prevent during cold and flu season. Most recently, we have fall vaccinations aimed to prevent COVID-19, influenza, and respiratory syncytial virus (RSV).

The number and timing of each of these vaccinations has different recommendations based on a variety of factors including age, pregnancy status, and whether or not the patient is immunocompromised. For the 2024-2025 season, the Centers for Disease Control and Prevention has recommended updated vaccines for both influenza and COVID-19.¹

They have also updated the RSV vaccine recommendations to “People 75 or older, or between 60-74 with certain chronic health conditions or living in a nursing home should get one dose of the RSV vaccine to provide an extra layer of protection.”²

In addition to vaccines as prevention, there is also hygiene, staying home when sick and away from others who are sick, following guidelines for where and when to wear a face mask, and the general tools of eating well, and getting sufficient sleep and exercise to help maintain the healthiest immune system.

Despite the best of intentions, there will still be many who experience viral infections in this upcoming season. The CDC is currently recommending persons to stay away from others for at least 24 hours after their symptoms improve and they are fever-free without antipyretics. In addition to isolation while sick, general symptom management is something that we can recommend for all of these illnesses.

There is more to consider, though, as our patients face these illnesses. The first question is how to determine the diagnosis — and if that diagnosis is even necessary. Unfortunately, many of these viral illnesses can look the same. They can all cause fevers, chills, and other upper respiratory symptoms. They are all fairly contagious. All of these viruses can cause serious illness associated with additional complications. It is not truly possible to determine which virus someone has by symptoms alone, our patients can have multiple viruses at the same time and diagnosis of one does not preclude having another.³

Instead, we truly do need a test for diagnosis. In-office testing is available for RSV, influenza, and COVID-19. Additionally, despite not being as freely available as they were during the pandemic, patients are able to do home COVID tests and then call in with their results. At the time of writing this, at-home rapid influenza tests have also been approved by the FDA but are not yet readily available to the public. These tests are important for determining if the patient is eligible for treatment. Both influenza and COVID-19 have antiviral treatments available to help decrease the severity of the illness and potentially the length of illness and time contagious. According to the CDC, both treatments are underutilized.

This could be because of a lack of testing and diagnosis. It may also be because of a lack of familiarity with the available treatments.^4,5

Influenza treatment is recommended as soon as possible for those with suspected or confirmed diagnosis, immediately for anyone hospitalized, anyone with severe, complicated, or progressing illness, and for those at high risk of severe illness including but not limited to those under 2 years old, those over 65, those who are pregnant, and those with many chronic conditions.

Treatment can also be used for those who are not high risk when diagnosed within 48 hours. In the United States, four antivirals are recommended to treat influenza: oseltamivir phosphate, zanamivir, peramivir, and baloxavir marboxil. For COVID-19, treatments are also available for mild or moderate disease in those at risk for severe disease. Both remdesivir and nimatrelvir with ritonavir are treatment options that can be used for COVID-19 infection. Unfortunately, no specific antiviral is available for the other viral illnesses we see often during this season.

In primary care, we have some important roles to play. We need to continue to discuss all methods of prevention. Not only do vaccine recommendations change at least annually, our patients’ situations change and we have to reassess them. Additionally, people often need to hear things more than once before committing — so it never hurts to continue having those conversations. Combining the conversation about vaccines with other prevention measures is also important so that it does not seem like we are only recommending one thing. We should also start talking about treatment options before our patients are sick. We can communicate what is available as long as they let us know they are sick early. We can also be there to help our patients determine when they are at risk for severe illness and when they should consider a higher level of care.

The availability of home testing gives us the opportunity to provide these treatments via telehealth and even potentially in times when these illnesses are everywhere — with standing orders with our clinical teams. Although it is a busy time for us in the clinic, “cold and flu” season is definitely one of those times when our primary care relationship can truly help our patients.
 

References

1. CDC Recommends Updated 2024-2025 COVID-19 and Flu Vaccines for Fall/Winter Virus Season. https://www.cdc.gov/media/releases/2024/s-t0627-vaccine-recommendations.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

2. CDC Updates RSV Vaccination Recommendation for Adults. https://www.cdc.gov/media/releases/2024/s-0626-vaccination-adults.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

3. Similarities and Differences between Flu and COVID-19. https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases.

4. Respiratory Virus Guidance. https://www.cdc.gov/respiratory-viruses/guidance/index.html. Accessed August 9, 2024. Source: National Center for Immunization and Respiratory Diseases.

5. Provider Toolkit: Preparing Patients for the Fall and Winter Virus Season. https://www.cdc.gov/respiratory-viruses/hcp/tools-resources/index.html. Accessed August 9, 2024. Source: Centers for Disease Control and Prevention.

We are quickly approaching the typical cold and flu season. But can we call anything typical since 2020? Since 2020, there have been different recommendations for prevention, testing, return to work, and treatment since our world was rocked by the pandemic. Now that we are in the “post-pandemic” era, family physicians and other primary care professionals are the front line for discussions on prevention, evaluation, and treatment of the typical upper-respiratory infections, influenza, and COVID-19.

Let’s start with prevention. We have all heard the old adage, an ounce of prevention is worth a pound of cure. In primary care, we need to focus on prevention. Vaccination is often one of our best tools against the myriad of infections we are hoping to help patients prevent during cold and flu season. Most recently, we have fall vaccinations aimed to prevent COVID-19, influenza, and respiratory syncytial virus (RSV).

The number and timing of each of these vaccinations has different recommendations based on a variety of factors including age, pregnancy status, and whether or not the patient is immunocompromised. For the 2024-2025 season, the Centers for Disease Control and Prevention has recommended updated vaccines for both influenza and COVID-19.¹

They have also updated the RSV vaccine recommendations to “People 75 or older, or between 60-74 with certain chronic health conditions or living in a nursing home should get one dose of the RSV vaccine to provide an extra layer of protection.”²

In addition to vaccines as prevention, there is also hygiene, staying home when sick and away from others who are sick, following guidelines for where and when to wear a face mask, and the general tools of eating well, and getting sufficient sleep and exercise to help maintain the healthiest immune system.

Despite the best of intentions, there will still be many who experience viral infections in this upcoming season. The CDC is currently recommending persons to stay away from others for at least 24 hours after their symptoms improve and they are fever-free without antipyretics. In addition to isolation while sick, general symptom management is something that we can recommend for all of these illnesses.

There is more to consider, though, as our patients face these illnesses. The first question is how to determine the diagnosis — and if that diagnosis is even necessary. Unfortunately, many of these viral illnesses can look the same. They can all cause fevers, chills, and other upper respiratory symptoms. They are all fairly contagious. All of these viruses can cause serious illness associated with additional complications. It is not truly possible to determine which virus someone has by symptoms alone, our patients can have multiple viruses at the same time and diagnosis of one does not preclude having another.³

Instead, we truly do need a test for diagnosis. In-office testing is available for RSV, influenza, and COVID-19. Additionally, despite not being as freely available as they were during the pandemic, patients are able to do home COVID tests and then call in with their results. At the time of writing this, at-home rapid influenza tests have also been approved by the FDA but are not yet readily available to the public. These tests are important for determining if the patient is eligible for treatment. Both influenza and COVID-19 have antiviral treatments available to help decrease the severity of the illness and potentially the length of illness and time contagious. According to the CDC, both treatments are underutilized.

This could be because of a lack of testing and diagnosis. It may also be because of a lack of familiarity with the available treatments.^4,5

Influenza treatment is recommended as soon as possible for those with suspected or confirmed diagnosis, immediately for anyone hospitalized, anyone with severe, complicated, or progressing illness, and for those at high risk of severe illness including but not limited to those under 2 years old, those over 65, those who are pregnant, and those with many chronic conditions.

Treatment can also be used for those who are not high risk when diagnosed within 48 hours. In the United States, four antivirals are recommended to treat influenza: oseltamivir phosphate, zanamivir, peramivir, and baloxavir marboxil. For COVID-19, treatments are also available for mild or moderate disease in those at risk for severe disease. Both remdesivir and nimatrelvir with ritonavir are treatment options that can be used for COVID-19 infection. Unfortunately, no specific antiviral is available for the other viral illnesses we see often during this season.

In primary care, we have some important roles to play. We need to continue to discuss all methods of prevention. Not only do vaccine recommendations change at least annually, our patients’ situations change and we have to reassess them. Additionally, people often need to hear things more than once before committing — so it never hurts to continue having those conversations. Combining the conversation about vaccines with other prevention measures is also important so that it does not seem like we are only recommending one thing. We should also start talking about treatment options before our patients are sick. We can communicate what is available as long as they let us know they are sick early. We can also be there to help our patients determine when they are at risk for severe illness and when they should consider a higher level of care.

The availability of home testing gives us the opportunity to provide these treatments via telehealth and even potentially in times when these illnesses are everywhere — with standing orders with our clinical teams. Although it is a busy time for us in the clinic, “cold and flu” season is definitely one of those times when our primary care relationship can truly help our patients.
 

References

1. CDC Recommends Updated 2024-2025 COVID-19 and Flu Vaccines for Fall/Winter Virus Season. https://www.cdc.gov/media/releases/2024/s-t0627-vaccine-recommendations.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

2. CDC Updates RSV Vaccination Recommendation for Adults. https://www.cdc.gov/media/releases/2024/s-0626-vaccination-adults.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

3. Similarities and Differences between Flu and COVID-19. https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases.

4. Respiratory Virus Guidance. https://www.cdc.gov/respiratory-viruses/guidance/index.html. Accessed August 9, 2024. Source: National Center for Immunization and Respiratory Diseases.

5. Provider Toolkit: Preparing Patients for the Fall and Winter Virus Season. https://www.cdc.gov/respiratory-viruses/hcp/tools-resources/index.html. Accessed August 9, 2024. Source: Centers for Disease Control and Prevention.

We are quickly approaching the typical cold and flu season. But can we call anything typical since 2020? Since 2020, there have been different recommendations for prevention, testing, return to work, and treatment since our world was rocked by the pandemic. Now that we are in the “post-pandemic” era, family physicians and other primary care professionals are the front line for discussions on prevention, evaluation, and treatment of the typical upper-respiratory infections, influenza, and COVID-19.

Let’s start with prevention. We have all heard the old adage, an ounce of prevention is worth a pound of cure. In primary care, we need to focus on prevention. Vaccination is often one of our best tools against the myriad of infections we are hoping to help patients prevent during cold and flu season. Most recently, we have fall vaccinations aimed to prevent COVID-19, influenza, and respiratory syncytial virus (RSV).

The number and timing of each of these vaccinations has different recommendations based on a variety of factors including age, pregnancy status, and whether or not the patient is immunocompromised. For the 2024-2025 season, the Centers for Disease Control and Prevention has recommended updated vaccines for both influenza and COVID-19.¹

They have also updated the RSV vaccine recommendations to “People 75 or older, or between 60-74 with certain chronic health conditions or living in a nursing home should get one dose of the RSV vaccine to provide an extra layer of protection.”²

In addition to vaccines as prevention, there is also hygiene, staying home when sick and away from others who are sick, following guidelines for where and when to wear a face mask, and the general tools of eating well, and getting sufficient sleep and exercise to help maintain the healthiest immune system.

Despite the best of intentions, there will still be many who experience viral infections in this upcoming season. The CDC is currently recommending persons to stay away from others for at least 24 hours after their symptoms improve and they are fever-free without antipyretics. In addition to isolation while sick, general symptom management is something that we can recommend for all of these illnesses.

There is more to consider, though, as our patients face these illnesses. The first question is how to determine the diagnosis — and if that diagnosis is even necessary. Unfortunately, many of these viral illnesses can look the same. They can all cause fevers, chills, and other upper respiratory symptoms. They are all fairly contagious. All of these viruses can cause serious illness associated with additional complications. It is not truly possible to determine which virus someone has by symptoms alone, our patients can have multiple viruses at the same time and diagnosis of one does not preclude having another.³

Instead, we truly do need a test for diagnosis. In-office testing is available for RSV, influenza, and COVID-19. Additionally, despite not being as freely available as they were during the pandemic, patients are able to do home COVID tests and then call in with their results. At the time of writing this, at-home rapid influenza tests have also been approved by the FDA but are not yet readily available to the public. These tests are important for determining if the patient is eligible for treatment. Both influenza and COVID-19 have antiviral treatments available to help decrease the severity of the illness and potentially the length of illness and time contagious. According to the CDC, both treatments are underutilized.

This could be because of a lack of testing and diagnosis. It may also be because of a lack of familiarity with the available treatments.^4,5

Influenza treatment is recommended as soon as possible for those with suspected or confirmed diagnosis, immediately for anyone hospitalized, anyone with severe, complicated, or progressing illness, and for those at high risk of severe illness including but not limited to those under 2 years old, those over 65, those who are pregnant, and those with many chronic conditions.

Treatment can also be used for those who are not high risk when diagnosed within 48 hours. In the United States, four antivirals are recommended to treat influenza: oseltamivir phosphate, zanamivir, peramivir, and baloxavir marboxil. For COVID-19, treatments are also available for mild or moderate disease in those at risk for severe disease. Both remdesivir and nimatrelvir with ritonavir are treatment options that can be used for COVID-19 infection. Unfortunately, no specific antiviral is available for the other viral illnesses we see often during this season.

In primary care, we have some important roles to play. We need to continue to discuss all methods of prevention. Not only do vaccine recommendations change at least annually, our patients’ situations change and we have to reassess them. Additionally, people often need to hear things more than once before committing — so it never hurts to continue having those conversations. Combining the conversation about vaccines with other prevention measures is also important so that it does not seem like we are only recommending one thing. We should also start talking about treatment options before our patients are sick. We can communicate what is available as long as they let us know they are sick early. We can also be there to help our patients determine when they are at risk for severe illness and when they should consider a higher level of care.

The availability of home testing gives us the opportunity to provide these treatments via telehealth and even potentially in times when these illnesses are everywhere — with standing orders with our clinical teams. Although it is a busy time for us in the clinic, “cold and flu” season is definitely one of those times when our primary care relationship can truly help our patients.
 

References

1. CDC Recommends Updated 2024-2025 COVID-19 and Flu Vaccines for Fall/Winter Virus Season. https://www.cdc.gov/media/releases/2024/s-t0627-vaccine-recommendations.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

2. CDC Updates RSV Vaccination Recommendation for Adults. https://www.cdc.gov/media/releases/2024/s-0626-vaccination-adults.html. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention.

3. Similarities and Differences between Flu and COVID-19. https://www.cdc.gov/flu/symptoms/flu-vs-covid19.htm. Accessed August 8, 2024. Source: Centers for Disease Control and Prevention, National Center for Immunization and Respiratory Diseases.

4. Respiratory Virus Guidance. https://www.cdc.gov/respiratory-viruses/guidance/index.html. Accessed August 9, 2024. Source: National Center for Immunization and Respiratory Diseases.

5. Provider Toolkit: Preparing Patients for the Fall and Winter Virus Season. https://www.cdc.gov/respiratory-viruses/hcp/tools-resources/index.html. Accessed August 9, 2024. Source: Centers for Disease Control and Prevention.

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

TOPLINE:

The maternal and neonatal outcomes in pregnant women treated with anti–interleukin (IL)-6 therapy for COVID-19 are largely favorable, with transient neonatal cytopenia observed in around one third of the babies being the only possible adverse outcome that could be related to anti–IL-6 therapy.

METHODOLOGY:

• Despite guidance, very few pregnant women with COVID-19 are offered evidence-based therapies such as anti–IL-6 due to concerns regarding fetal safety in later pregnancy.
• In this retrospective study, researchers evaluated maternal and neonatal outcomes in 25 pregnant women with COVID-19 (mean age at admission, 33 years) treated with anti–IL-6 (tocilizumab or sarilumab) at two tertiary hospitals in London.
• Most women (n = 16) received anti–IL-6 in the third trimester of pregnancy, whereas nine received it during the second trimester.
• Maternal and neonatal outcomes were assessed through medical record reviews and maternal medicine networks, with follow-up for 12 months.
• The women included in the study constituted a high-risk population with severe COVID-19; 24 required level two or three critical care. All women were receiving at least three concomitant medications due to their critical illness.

TAKEAWAY:

• Overall, 24 of 25 women treated with IL-6 receptor antibodies survived until hospital discharge.
• The sole death occurred in a woman with severe COVID-19 pneumonitis who later developed myocarditis and cardiac arrest. The physicians believed that these complications were more likely due to severe COVID-19 rather than anti–IL-6 therapy.
• All pregnancies resulted in live births; however, 16 babies had to be delivered preterm due to COVID-19 complications.
• Transient cytopenia was observed in 6 of 19 babies in whom a full blood count was performed. All the six babies were premature, with cytopenia resolving within 7 days in four babies; one baby died from complications associated with extreme prematurity.

IN PRACTICE:

“Although the authors found mild, transitory cytopenia in some (6 of 19) exposed infants, most had been delivered prematurely due to progressive COVID-19–related morbidity, and distinguishing drug effects from similar prematurity-related effects is difficult,” wrote Steven L. Clark, MD, from the Department of Obstetrics and Gynecology, Baylor College of Medicine, Houston, in an accompanying editorial.

SOURCE:

The study was led by Melanie Nana, MRCP, from the Department of Obstetric Medicine, St Thomas’ Hospital, London, England. It was published online in The Lancet Rheumatology.

LIMITATIONS:

The study was retrospective in design, which may have introduced bias. The small sample size of 25 women may have limited the generalizability of the findings. Additionally, the study did not include a control group, which made it difficult to attribute outcomes solely to anti–IL-6 therapy. The lack of long-term follow-up data on the neonates also limited the understanding of potential long-term effects.

DISCLOSURES:

This study did not receive any funding. Some authors, including the lead author, received speaker fees, grants, or consultancy fees from academic institutions or pharmaceutical companies or had other ties with various sources.

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

An estimated two million people in England and Scotland were experiencing symptoms of long COVID as of March 2024, according to the Office for National Statistics. Of these, 1.5 million said the condition was adversely affecting their day-to-day activities.

As more research emerges about long COVID, some experts are noticing that its trigger factors, symptoms, and causative mechanisms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

ME/CFS is characterized by severe fatigue that does not improve with rest, in addition to pain and cognitive problems. One in four patients are bed- or house-bound with severe forms of the condition, sometimes experiencing atypical seizures, and speech and swallowing difficulties.

Despite affecting around 250,000 people in the UK and around 2 million people in the European Union (EU), it is a relatively poorly funded disease research area. Increased research into long COVID is thus providing a much-needed boost to ME/CFS research.

“What we already know about the possible causation of ME/CFS is helping research into the causes of long COVID. At the same time, research into long COVID is opening up new avenues of research that may also be relevant to ME/CFS. It is becoming a two-way process,” Dr. Charles Shepherd, honorary medical adviser to the UK-based ME Association, told this news organization.

While funding remains an issue, promising research is currently underway in the UK to improve diagnosis, treatment, and understanding of the pathology of ME/CFS.
 

Viral Reactivation

Dr. David Newton is research director at ME Research UK. “Viral infection is commonly reported as a trigger for [ME/CFS, meaning that the disease] may be caused by reactivation of latent viruses, including human herpes viruses and enteroviruses,” he said.

Herpes viruses can lie dormant in their host’s immune system for long periods of time. They can be reactivated by factors including infections, stress, and a weakened immune system, and may cause temporary symptoms or persistent disease.

A 2021 pilot study found that people with ME/CFS have a higher concentration of human herpesvirus 6B (HHV-6B) DNA in their saliva, and that concentration correlates with symptom severity. HHV-6B is a common virus typically contracted during infancy and childhood.

A continuation of this research is now underway at Brunel University to improve understanding of HHV-6B’s role in the onset and progression of ME/CFS, and to support the development of diagnostic and prognostic markers, as well as therapeutics such as antiviral therapies.
 

Mitochondrial Dysfunction

Dr. Shepherd explained that there is now sound evidence demonstrating that biochemical abnormalities in ME/CFS affect how mitochondria produce energy after physical exertion. Research is thus underway to see if treating mitochondrial dysfunction improves ME/CFS symptoms.

A phase 2a placebo-controlled clinical trial from 2023 found that AXA1125, a drug that works by modulating energy metabolism, significantly improved symptoms of fatigue in patients with fatigue-dominant long COVID, although it did not improve mitochondrial respiration.

“[The findings suggest] that improving mitochondrial health may be one way to restore normal functioning among people with long COVID, and by extension CFS,” study author Betty Raman, associate professor of cardiovascular medicine at the University of Oxford, told this news organization. She noted, however, that plans for a phase III trial have stalled due to insufficient funding.

Meanwhile, researchers from the Quadram Institute in Norwich and the University of East Anglia are conducting a pilot study to see if red light therapy can relieve symptoms of ME/CFS. Red light can be absorbed by mitochondria and is used to boost energy production. The trial will monitor patients remotely from their homes and will assess cognitive function and physical activity levels.
 

Gut Dysbiosis

Many studies have found that people with ME/CFS have altered gut microbiota, which suggests that changes in gut bacteria may contribute to the condition. Researchers at the Quadram Institute will thus conduct a clinical trial called RESTORE-ME to see whether fecal microbiota transplants (FMT) can treat the condition.

Rik Haagmans is a research scientist and PhD candidate at the Quadram Institute. He told this news organization: “Our FMT studies, if effective, could provide a longer lasting or even permanent relief of ME/CFS, as restoring the gut microbial composition wouldn’t require continuous medication,” he said.
 

Biobank and Biomarkers

Europe’s first ME/CFS-specific biobank is in the UK and is called UKMEB. It now has more than 30,000 blood samples from patients with ME/CFS, multiple sclerosis, and healthy controls. Uniquely, it includes samples from people with ME/CFS who are house- and bed-bound. Caroline Kingdon, RN, MSc, a research fellow and biobank lead at the London School of Hygiene and Tropical Medicine, told this news organization that samples and data from the UKMEB have been provided to research groups all over the world and have contributed to widely cited literature.

One group making use of these samples is led by Fatima Labeed, PhD, senior lecturer in human biology at the University of Surrey. Dr. Labeed and her team are developing a diagnostic test for ME/CFS based on electrical properties in white blood cells.

“To date, studies of ME/CFS have focused on the biochemical behavior of cells: the amount and type of proteins that cells use. We have taken a different approach, studying the electrical properties,” she explained to this news organization.

Her research builds on initial observations from 2019 that found differences in the electrical impedance of white blood cells between people with ME/CFS and controls. While the biological implications remain unknown, the findings may represent a biomarker for the condition.

Using blood samples from the UKMEB, the researchers are now investigating this potential biomarker with improved techniques and a larger patient cohort, including those with mild/moderate and severe forms of ME/CFS. So far, they have received more than 100 blood samples and have analyzed the electrical properties of 42.

“Based on the results we have so far, we are very close to having a biomarker for diagnosis. Our results so far show a high degree of accuracy and are able to distinguish between ME/CFS and other diseases,” said Dr. Labeed.
 

Genetic Test

Another promising avenue for diagnostics comes from a research team at the University of Edinburgh led by Professor Chris Ponting at the university’s Institute of Genetics and Cancer. They are currently working on DecodeMe, a large genetic study of ME using data from more than 26,000 people.

“We are studying blood-based biomarkers that distinguish people with ME from population controls. We’ve found a large number — including some found previously in other studies — and are writing these results up for publication,” said Ponting. The results should be published in early 2025.
 

The Future

While research into ME/CFS has picked up pace in recent years, funding remains a key bottleneck.

“Over the last 10 years, only £8.05m has been spent on ME research,” Sonya Chowdhury, chief executive of UK charity Action for ME told this news organization. She believes this amount is not equitably comparable to research funding allocated to other diseases.

In 2022, the UK government announced its intention to develop a cross-government interim delivery plan on ME/CFS for England, however publication of the final plan has been delayed numerous times.

Dr. Shepherd agreed that increased funding is crucial for progress to be made. He said the biggest help to ME/CFS research would be to end the disparity in government research funding for the disease, and match what is given for many other disabling long-term conditions.

“It’s not fair to continue to rely on the charity sector to fund almost all of the biomedical research into ME/CFS here in the UK,” he said.

A version of this article appeared on Medscape.com.

An estimated two million people in England and Scotland were experiencing symptoms of long COVID as of March 2024, according to the Office for National Statistics. Of these, 1.5 million said the condition was adversely affecting their day-to-day activities.

As more research emerges about long COVID, some experts are noticing that its trigger factors, symptoms, and causative mechanisms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

ME/CFS is characterized by severe fatigue that does not improve with rest, in addition to pain and cognitive problems. One in four patients are bed- or house-bound with severe forms of the condition, sometimes experiencing atypical seizures, and speech and swallowing difficulties.

Despite affecting around 250,000 people in the UK and around 2 million people in the European Union (EU), it is a relatively poorly funded disease research area. Increased research into long COVID is thus providing a much-needed boost to ME/CFS research.

“What we already know about the possible causation of ME/CFS is helping research into the causes of long COVID. At the same time, research into long COVID is opening up new avenues of research that may also be relevant to ME/CFS. It is becoming a two-way process,” Dr. Charles Shepherd, honorary medical adviser to the UK-based ME Association, told this news organization.

While funding remains an issue, promising research is currently underway in the UK to improve diagnosis, treatment, and understanding of the pathology of ME/CFS.
 

Viral Reactivation

Dr. David Newton is research director at ME Research UK. “Viral infection is commonly reported as a trigger for [ME/CFS, meaning that the disease] may be caused by reactivation of latent viruses, including human herpes viruses and enteroviruses,” he said.

Herpes viruses can lie dormant in their host’s immune system for long periods of time. They can be reactivated by factors including infections, stress, and a weakened immune system, and may cause temporary symptoms or persistent disease.

A 2021 pilot study found that people with ME/CFS have a higher concentration of human herpesvirus 6B (HHV-6B) DNA in their saliva, and that concentration correlates with symptom severity. HHV-6B is a common virus typically contracted during infancy and childhood.

A continuation of this research is now underway at Brunel University to improve understanding of HHV-6B’s role in the onset and progression of ME/CFS, and to support the development of diagnostic and prognostic markers, as well as therapeutics such as antiviral therapies.
 

Mitochondrial Dysfunction

Dr. Shepherd explained that there is now sound evidence demonstrating that biochemical abnormalities in ME/CFS affect how mitochondria produce energy after physical exertion. Research is thus underway to see if treating mitochondrial dysfunction improves ME/CFS symptoms.

A phase 2a placebo-controlled clinical trial from 2023 found that AXA1125, a drug that works by modulating energy metabolism, significantly improved symptoms of fatigue in patients with fatigue-dominant long COVID, although it did not improve mitochondrial respiration.

“[The findings suggest] that improving mitochondrial health may be one way to restore normal functioning among people with long COVID, and by extension CFS,” study author Betty Raman, associate professor of cardiovascular medicine at the University of Oxford, told this news organization. She noted, however, that plans for a phase III trial have stalled due to insufficient funding.

Meanwhile, researchers from the Quadram Institute in Norwich and the University of East Anglia are conducting a pilot study to see if red light therapy can relieve symptoms of ME/CFS. Red light can be absorbed by mitochondria and is used to boost energy production. The trial will monitor patients remotely from their homes and will assess cognitive function and physical activity levels.
 

Gut Dysbiosis

Many studies have found that people with ME/CFS have altered gut microbiota, which suggests that changes in gut bacteria may contribute to the condition. Researchers at the Quadram Institute will thus conduct a clinical trial called RESTORE-ME to see whether fecal microbiota transplants (FMT) can treat the condition.

Rik Haagmans is a research scientist and PhD candidate at the Quadram Institute. He told this news organization: “Our FMT studies, if effective, could provide a longer lasting or even permanent relief of ME/CFS, as restoring the gut microbial composition wouldn’t require continuous medication,” he said.
 

Biobank and Biomarkers

Europe’s first ME/CFS-specific biobank is in the UK and is called UKMEB. It now has more than 30,000 blood samples from patients with ME/CFS, multiple sclerosis, and healthy controls. Uniquely, it includes samples from people with ME/CFS who are house- and bed-bound. Caroline Kingdon, RN, MSc, a research fellow and biobank lead at the London School of Hygiene and Tropical Medicine, told this news organization that samples and data from the UKMEB have been provided to research groups all over the world and have contributed to widely cited literature.

One group making use of these samples is led by Fatima Labeed, PhD, senior lecturer in human biology at the University of Surrey. Dr. Labeed and her team are developing a diagnostic test for ME/CFS based on electrical properties in white blood cells.

“To date, studies of ME/CFS have focused on the biochemical behavior of cells: the amount and type of proteins that cells use. We have taken a different approach, studying the electrical properties,” she explained to this news organization.

Her research builds on initial observations from 2019 that found differences in the electrical impedance of white blood cells between people with ME/CFS and controls. While the biological implications remain unknown, the findings may represent a biomarker for the condition.

Using blood samples from the UKMEB, the researchers are now investigating this potential biomarker with improved techniques and a larger patient cohort, including those with mild/moderate and severe forms of ME/CFS. So far, they have received more than 100 blood samples and have analyzed the electrical properties of 42.

“Based on the results we have so far, we are very close to having a biomarker for diagnosis. Our results so far show a high degree of accuracy and are able to distinguish between ME/CFS and other diseases,” said Dr. Labeed.
 

Genetic Test

Another promising avenue for diagnostics comes from a research team at the University of Edinburgh led by Professor Chris Ponting at the university’s Institute of Genetics and Cancer. They are currently working on DecodeMe, a large genetic study of ME using data from more than 26,000 people.

“We are studying blood-based biomarkers that distinguish people with ME from population controls. We’ve found a large number — including some found previously in other studies — and are writing these results up for publication,” said Ponting. The results should be published in early 2025.
 

The Future

While research into ME/CFS has picked up pace in recent years, funding remains a key bottleneck.

“Over the last 10 years, only £8.05m has been spent on ME research,” Sonya Chowdhury, chief executive of UK charity Action for ME told this news organization. She believes this amount is not equitably comparable to research funding allocated to other diseases.

In 2022, the UK government announced its intention to develop a cross-government interim delivery plan on ME/CFS for England, however publication of the final plan has been delayed numerous times.

Dr. Shepherd agreed that increased funding is crucial for progress to be made. He said the biggest help to ME/CFS research would be to end the disparity in government research funding for the disease, and match what is given for many other disabling long-term conditions.

“It’s not fair to continue to rely on the charity sector to fund almost all of the biomedical research into ME/CFS here in the UK,” he said.

A version of this article appeared on Medscape.com.

An estimated two million people in England and Scotland were experiencing symptoms of long COVID as of March 2024, according to the Office for National Statistics. Of these, 1.5 million said the condition was adversely affecting their day-to-day activities.

As more research emerges about long COVID, some experts are noticing that its trigger factors, symptoms, and causative mechanisms overlap with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS).

ME/CFS is characterized by severe fatigue that does not improve with rest, in addition to pain and cognitive problems. One in four patients are bed- or house-bound with severe forms of the condition, sometimes experiencing atypical seizures, and speech and swallowing difficulties.

Despite affecting around 250,000 people in the UK and around 2 million people in the European Union (EU), it is a relatively poorly funded disease research area. Increased research into long COVID is thus providing a much-needed boost to ME/CFS research.

“What we already know about the possible causation of ME/CFS is helping research into the causes of long COVID. At the same time, research into long COVID is opening up new avenues of research that may also be relevant to ME/CFS. It is becoming a two-way process,” Dr. Charles Shepherd, honorary medical adviser to the UK-based ME Association, told this news organization.

While funding remains an issue, promising research is currently underway in the UK to improve diagnosis, treatment, and understanding of the pathology of ME/CFS.
 

Viral Reactivation

Dr. David Newton is research director at ME Research UK. “Viral infection is commonly reported as a trigger for [ME/CFS, meaning that the disease] may be caused by reactivation of latent viruses, including human herpes viruses and enteroviruses,” he said.

Herpes viruses can lie dormant in their host’s immune system for long periods of time. They can be reactivated by factors including infections, stress, and a weakened immune system, and may cause temporary symptoms or persistent disease.

A 2021 pilot study found that people with ME/CFS have a higher concentration of human herpesvirus 6B (HHV-6B) DNA in their saliva, and that concentration correlates with symptom severity. HHV-6B is a common virus typically contracted during infancy and childhood.

A continuation of this research is now underway at Brunel University to improve understanding of HHV-6B’s role in the onset and progression of ME/CFS, and to support the development of diagnostic and prognostic markers, as well as therapeutics such as antiviral therapies.
 

Mitochondrial Dysfunction

Dr. Shepherd explained that there is now sound evidence demonstrating that biochemical abnormalities in ME/CFS affect how mitochondria produce energy after physical exertion. Research is thus underway to see if treating mitochondrial dysfunction improves ME/CFS symptoms.

A phase 2a placebo-controlled clinical trial from 2023 found that AXA1125, a drug that works by modulating energy metabolism, significantly improved symptoms of fatigue in patients with fatigue-dominant long COVID, although it did not improve mitochondrial respiration.

“[The findings suggest] that improving mitochondrial health may be one way to restore normal functioning among people with long COVID, and by extension CFS,” study author Betty Raman, associate professor of cardiovascular medicine at the University of Oxford, told this news organization. She noted, however, that plans for a phase III trial have stalled due to insufficient funding.

Meanwhile, researchers from the Quadram Institute in Norwich and the University of East Anglia are conducting a pilot study to see if red light therapy can relieve symptoms of ME/CFS. Red light can be absorbed by mitochondria and is used to boost energy production. The trial will monitor patients remotely from their homes and will assess cognitive function and physical activity levels.
 

Gut Dysbiosis

Many studies have found that people with ME/CFS have altered gut microbiota, which suggests that changes in gut bacteria may contribute to the condition. Researchers at the Quadram Institute will thus conduct a clinical trial called RESTORE-ME to see whether fecal microbiota transplants (FMT) can treat the condition.

Rik Haagmans is a research scientist and PhD candidate at the Quadram Institute. He told this news organization: “Our FMT studies, if effective, could provide a longer lasting or even permanent relief of ME/CFS, as restoring the gut microbial composition wouldn’t require continuous medication,” he said.
 

Biobank and Biomarkers

Europe’s first ME/CFS-specific biobank is in the UK and is called UKMEB. It now has more than 30,000 blood samples from patients with ME/CFS, multiple sclerosis, and healthy controls. Uniquely, it includes samples from people with ME/CFS who are house- and bed-bound. Caroline Kingdon, RN, MSc, a research fellow and biobank lead at the London School of Hygiene and Tropical Medicine, told this news organization that samples and data from the UKMEB have been provided to research groups all over the world and have contributed to widely cited literature.

One group making use of these samples is led by Fatima Labeed, PhD, senior lecturer in human biology at the University of Surrey. Dr. Labeed and her team are developing a diagnostic test for ME/CFS based on electrical properties in white blood cells.

“To date, studies of ME/CFS have focused on the biochemical behavior of cells: the amount and type of proteins that cells use. We have taken a different approach, studying the electrical properties,” she explained to this news organization.

Her research builds on initial observations from 2019 that found differences in the electrical impedance of white blood cells between people with ME/CFS and controls. While the biological implications remain unknown, the findings may represent a biomarker for the condition.

Using blood samples from the UKMEB, the researchers are now investigating this potential biomarker with improved techniques and a larger patient cohort, including those with mild/moderate and severe forms of ME/CFS. So far, they have received more than 100 blood samples and have analyzed the electrical properties of 42.

“Based on the results we have so far, we are very close to having a biomarker for diagnosis. Our results so far show a high degree of accuracy and are able to distinguish between ME/CFS and other diseases,” said Dr. Labeed.
 

Genetic Test

Another promising avenue for diagnostics comes from a research team at the University of Edinburgh led by Professor Chris Ponting at the university’s Institute of Genetics and Cancer. They are currently working on DecodeMe, a large genetic study of ME using data from more than 26,000 people.

“We are studying blood-based biomarkers that distinguish people with ME from population controls. We’ve found a large number — including some found previously in other studies — and are writing these results up for publication,” said Ponting. The results should be published in early 2025.
 

The Future

While research into ME/CFS has picked up pace in recent years, funding remains a key bottleneck.

“Over the last 10 years, only £8.05m has been spent on ME research,” Sonya Chowdhury, chief executive of UK charity Action for ME told this news organization. She believes this amount is not equitably comparable to research funding allocated to other diseases.

In 2022, the UK government announced its intention to develop a cross-government interim delivery plan on ME/CFS for England, however publication of the final plan has been delayed numerous times.

Dr. Shepherd agreed that increased funding is crucial for progress to be made. He said the biggest help to ME/CFS research would be to end the disparity in government research funding for the disease, and match what is given for many other disabling long-term conditions.

“It’s not fair to continue to rely on the charity sector to fund almost all of the biomedical research into ME/CFS here in the UK,” he said.

A version of this article appeared on Medscape.com.

Almost 1 in 10 pregnant people infected with COVID-19 end up developing long COVID, according to a study published in Obstetrics & Gynecology.

Researchers at University of Utah Health looked at the medical records of more than 1500 people who got COVID-19 while pregnant and checked their self-reported symptoms at least 6 months after infection, according to a news release from the school.

The scientists discovered that 9.3% of those people reported long COVID symptoms, such as fatigue and issues in their gut. 

To make sure those long COVID symptoms were not actually symptoms of pregnancy, the research team did a second analysis of people who reported symptoms more than 12 weeks after giving birth. The risk of long COVID was about the same as in the first analysis.

“It was surprising to me that the prevalence was that high,” Torri D. Metz, MD, vice chair for research of obstetrics and gynecology at the school and co-leader of the study, said in the release. “This is something that does continue to affect otherwise reasonably healthy and young populations.”

The school said this is the first study to look at long COVID risks in pregnant people. Previous research found other dangers for pregnant people who get COVID, such as a higher chance of hospitalization or death, or complications such as preterm birth.

In the general population, research shows that 10%-20% of people who get COVID develop long COVID.

Dr. Metz said healthcare providers need to remain alert about long COVID, including in pregnant people.

“We need to have this on our radar as we’re seeing patients. It’s something we really don’t want to miss. And we want to get people referred to appropriate specialists who treat long COVID,” she said.
 

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

Almost 1 in 10 pregnant people infected with COVID-19 end up developing long COVID, according to a study published in Obstetrics & Gynecology.

Researchers at University of Utah Health looked at the medical records of more than 1500 people who got COVID-19 while pregnant and checked their self-reported symptoms at least 6 months after infection, according to a news release from the school.

The scientists discovered that 9.3% of those people reported long COVID symptoms, such as fatigue and issues in their gut. 

To make sure those long COVID symptoms were not actually symptoms of pregnancy, the research team did a second analysis of people who reported symptoms more than 12 weeks after giving birth. The risk of long COVID was about the same as in the first analysis.

“It was surprising to me that the prevalence was that high,” Torri D. Metz, MD, vice chair for research of obstetrics and gynecology at the school and co-leader of the study, said in the release. “This is something that does continue to affect otherwise reasonably healthy and young populations.”

The school said this is the first study to look at long COVID risks in pregnant people. Previous research found other dangers for pregnant people who get COVID, such as a higher chance of hospitalization or death, or complications such as preterm birth.

In the general population, research shows that 10%-20% of people who get COVID develop long COVID.

Dr. Metz said healthcare providers need to remain alert about long COVID, including in pregnant people.

“We need to have this on our radar as we’re seeing patients. It’s something we really don’t want to miss. And we want to get people referred to appropriate specialists who treat long COVID,” she said.
 

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

Almost 1 in 10 pregnant people infected with COVID-19 end up developing long COVID, according to a study published in Obstetrics & Gynecology.

Researchers at University of Utah Health looked at the medical records of more than 1500 people who got COVID-19 while pregnant and checked their self-reported symptoms at least 6 months after infection, according to a news release from the school.

The scientists discovered that 9.3% of those people reported long COVID symptoms, such as fatigue and issues in their gut. 

To make sure those long COVID symptoms were not actually symptoms of pregnancy, the research team did a second analysis of people who reported symptoms more than 12 weeks after giving birth. The risk of long COVID was about the same as in the first analysis.

“It was surprising to me that the prevalence was that high,” Torri D. Metz, MD, vice chair for research of obstetrics and gynecology at the school and co-leader of the study, said in the release. “This is something that does continue to affect otherwise reasonably healthy and young populations.”

The school said this is the first study to look at long COVID risks in pregnant people. Previous research found other dangers for pregnant people who get COVID, such as a higher chance of hospitalization or death, or complications such as preterm birth.

In the general population, research shows that 10%-20% of people who get COVID develop long COVID.

Dr. Metz said healthcare providers need to remain alert about long COVID, including in pregnant people.

“We need to have this on our radar as we’re seeing patients. It’s something we really don’t want to miss. And we want to get people referred to appropriate specialists who treat long COVID,” she said.
 

A version of this article first appeared on WebMD.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.

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.