Immunology

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

Many people with inflammatory bowel disease (IBD) can mount a strong antibody response to a booster shot of an mRNA COVID-19 vaccine, including those who were unable to respond fully to an initial two-dose vaccine series, new evidence suggests.

Of the study participants, 93% had detectable antibodies after their initial vaccination series, which increased to 99.5% following an additional dose.

“Most IBD patients, including those who are immune suppressed and/or did not have detectable humoral immune responses following the initial mRNA COVID-19 vaccine series, demonstrate strong immune responses to additional doses of mRNA vaccines,” Michael D. Kappelman, MD, a pediatric gastroenterologist at the University of North Carolina at Chapel Hill, told this news organization.

“These data support an additional vaccine dose of mRNA vaccine in patients at risk for an inadequate response to the initial series,” he said.

Dr. Kappelman presented these findings on behalf of the PREVENT-COVID Study Group as an e-poster at the 17th congress of the European Crohn’s and Colitis Organisation.
 

A study design to measure boosters’ benefits

For people with Crohn’s disease or ulcerative colitis who are taking immunosuppressants, boosters are generally recommended, Dr. Kappelman and colleagues noted. However, “real-world data on the effectiveness and safety of additional vaccine doses are lacking.”

They studied 659 people with IBD (mean age, 45 years; 72% female), of whom 72% had Crohn’s disease and 27% had ulcerative colitis/unclassified IBD.

Of these participants, 63% received Pfizer/BioNTech vaccine and 37% received the Moderna vaccine. Five participants received the Johnson & Johnson vaccine. In 98% of cases, people who received an mRNA vaccine initially also received the same type for the additional dose.

Participants completed baseline and follow-up surveys. Their blood work was obtained and evaluated 8 weeks after completion of the initial vaccine series and 6 weeks after a booster to measure anti–receptor binding domain IgG antibody levels specific to SARS-CoV-2.

Mean increase in antibody levels was 61 µg/mL in the Pfizer vaccine group and 78 µg/mL in the Moderna vaccine group following the booster shot.

Of the 47 patients without initial antibody response, 45 (96%) had detectable antibodies following an additional dose.

Serious adverse events (AEs) associated with the booster were rare, Dr. Kappelman said. Among participants, 44% reported no AEs, 24% mild AEs, 25% moderate AEs, and 6% reported serious AEs.

“These data can be used to inform vaccine decisions in patients with a broad array of immune-medicated conditions frequently managed by immunosuppression,” the investigators note.
 

A ‘reassuring’ finding

“This abstract [gives us] an important understanding about how patients with inflammatory bowel disease respond to COVID-19 vaccination. There have been mixed reports in the prior studies regarding how well patients with IBD respond to vaccination,” Jason Ken Hou, MD, said when asked to comment on the research.

The main findings that 99.5% of patients had detectable antibodies after an additional dose “is reassuring, as prior studies have suggested some patients did not develop antibodies after the [initial series],” added Dr. Hou, associate professor of medicine-gastroenterology at Baylor College of Medicine in Houston.

The researchers conducted the study within a previously established, well-known Internet-based cohort of IBD patients, Dr. Hou said. Although the researchers collected information on the IBD medications that patients were taking at the time of vaccination, the analyses that were presented did not compare antibody response rates based on medication.

“Further study is still required, as there is more to vaccination response than detectable antibody alone,” he added.

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

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at imnews@mdedge.com.

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at imnews@mdedge.com.

It would be overused and trite to say that the pandemic has drastically altered all of our lives and will cause lasting impact on how we function in society and medicine for years to come. While it seems that the current trend of the latest Omicron variant is on the downslope, the path to get to this point has been fraught with challenges that have struck at the very core of our society. As a primary care physician on the front lines seeing COVID patients, I have had to deal with not only the disease but the politics around it. As critical and life saving as the vaccines have been, many physicians have not been able to get access to these vaccines and give them to their patients. I am one of those physicians. I practice in Florida, and I still cannot give COVID vaccines in my office. 

I am a firm believer in the ability for physicians to be able to give all the necessary adult vaccines and provide them for their patients. The COVID vaccine exacerbated a majorly flawed system that further increased the health care disparities in the country. The current vaccine system for the majority of adult vaccines involves the physician’s being able to directly purchase supplies from the vaccine manufacturer, administer them to the patients, and be reimbursed.
 

Third parties can purchase vaccines at lower rates than those for physicians

The Affordable Care Act mandates that all vaccines approved by the Advisory Committee on Immunization Practices (ACIP) at the Centers for Disease Control and Prevention must be covered. This allows for better access to care as physicians will be able to purchase, store, and deliver vaccines to their patients. The fallacy in this system is that third parties get involved and rebates or incentives are given to these groups to purchase vaccines at a rate lower than those for physicians.

In addition, many organizations can get access to vaccines before physicians and at a lower cost. That system was flawed to begin with and created a deterrent for access to care and physician involvement in the vaccination process. This was worsened by different states being given the ability to decide how vaccines would be distributed for COVID.

Many pharmacies were able to give out COVID vaccines while many physician offices still have not received access to any of the vaccines. One of the major safety issues with this is that no physicians were involved in the administration of the vaccine, and it is unclear what training was given to the individuals injecting that vaccine. Finally, different places were interpreting the recommendations from ACIP on their own and not necessarily following the appropriate guidelines. All of these factors have further widened the health care disparity gap and made it difficult to provide the COVID vaccines in doctors’ offices.
 

Recommended next steps, solutions to problem

The question is what to do about this. The most important thing is to get the vaccines in arms so they can save lives. In addition, doctors need to be able to get the vaccines in their offices.

Many patients trust their physicians to advise them on what to do regarding health care. The majority of patients want to know if they should get the vaccine and ask for counseling. Physicians answering patients’ questions about vaccines is an important step in overcoming vaccine hesitancy.

Also, doctors need to be informed and supportive of the vaccine process.

The next step is the governmental aspect with those in power making sure that vaccines are accessible to all. Even if the vaccine cannot be given in the office, doctors should still be recommending that patients receive them. Plus, doctors should take every opportunity to ask about what vaccines their patients have received and encourage their patients to get vaccinated.

The COVID-19 vaccines are safe and effective and have been monitored for safety more than any other vaccine. There are multiple systems in place to look for any signals that could indicate an issue was caused by a COVID-19 vaccine. These vaccines can be administered with other vaccines, and there is a great opportunity for physicians to encourage patients to receive these life-saving vaccines.

While it may seem that the COVID-19 case counts are on the downslope, the importance of continuing to vaccinate is predicated on the very real concern that the disease is still circulating and the unvaccinated are still at risk for severe infection.

Dr. Goldman is immediate past governor of the Florida chapter of the American College of Physicians, a regent for the American College of Physicians, vice-president of the Florida Medical Association, and president of the Florida Medical Association Political Action Committee. You can reach Dr. Goldman at imnews@mdedge.com.

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

Longstanding anxiety around use of epinephrine autoinjectors has prompted research into alternative delivery routes for this life-saving medication. Several companies presented posters on their needle-free epinephrine products at the American Academy of Allergy, Asthma & Immunology (AAAAI) Annual Meeting.

Intranasal formulations are under development at ARS Pharmaceuticals (San Diego) and Bryn Pharma (Raleigh, N.C.). And Aquestive Therapeutics (Warren, N.J.) is working on a sublingual film that delivers epinephrine prodrug when applied under the tongue.

Epinephrine is essential for stopping life-threatening allergic reactions, yet patients often don’t carry their autoinjectors and many hesitate to use them. “It’s needle phobia,” said ARS Pharmaceuticals CEO Richard Lowenthal in an interview with this news organization. “They’re afraid to use it. They don’t like to inject their children, so they hesitate.” 

Both nasal sprays reached maximal plasma concentration in 20-30 minutes. ARS Pharmaceuticals compared its intranasal product (Neffy 1 mg) against manual intramuscular injection (0.3 mg) and two autoinjectors (EpiPen 0.3 mg and Symjepi 0.3 mg) by analyzing data from multiple randomized crossover Phase 1 studies examining pharmacokinetics and pharmacodynamics in 175 healthy adults. In this integrated analysis, EpiPen was fastest (20 minutes) at reaching maximal concentration (Tmax), followed by Symjepi and Neffy (both 30 minutes) and epinephrine 0.3 mg IM (45 minutes). In a human factors analysis, ARS Pharmaceuticals reported that untrained participants were able to administer the Neffy spray to themselves or another participant safely and effectively during a simulated emergency scenario.

Bryn Pharma compared pharmacokinetics of its nasal spray product (BRYN-NDS1C 6.6 mg) when self-administered or administered by trained professionals and found comparable profiles for each. Tmax values were also similar: 21.63 minutes (trained professional) and 19.82 minutes (self-administered).

Aquestive Therapeutics is developing a postage stamp-sized product (AQST-109) that delivers epinephrine and begins dissolving when placed under the tongue. No water or swallowing is required for administration, and its packaging is thinner and smaller than a credit card, according to CEO Keith Kendall. 

Its analysis showed that the epinephrine reaches maximum plasma concentration in about 15 minutes, with a Tmax range narrower than that of the EpiPen. “The results showed dosing with AQST-109 resulted in PK concentration and Tmax values comparable to published data from autoinjectors,” said John Oppenheimer, MD, of Rutgers University School of Medicine, in a prerecorded poster summary.

Aquestive aims to move forward to the manufacture of registration batches and a pivotal pharmacokinetic study in the second half of 2022. Mr. Lowenthal said ARS Pharmaceuticals is hoping for approval and launch of its nasal spray by summer 2023.

“Having a non-needle delivery device would help many people overcome that fear and hopefully increase use in anaphylaxis,” said David Stukus, MD, an allergist-immunologist and professor of clinical pediatrics at Nationwide Children’s Hospital, Columbus, who was not involved with any of the studies on EpiPen alternatives. And “it’s not just food allergy – anaphylaxis can occur from venom stings, medications, or idiopathic causes.”

Mr. Lowenthal is the CEO of ARS Pharmaceuticals. Mr. Kendall is CEO of Aquestive Therapeutics. Dr. Oppenheimer is a consultant for Aquestive, GSK, Amgen, Sanofi, and Aimmune and sits on Aquestive’s advisory board. Dr. Stukus is a consultant for Novartis.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

The American Academy of Pediatrics said it supports the Recommended Childhood and Adolescent Immunization Schedule: United States, 2022.

In a policy statement published online Feb. 17 in Pediatrics, the AAP said the updated recommendations differ little from those released last year by the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention.

“The only significant change this year was to add the dengue vaccine to the schedule,” Sean T. O’Leary, MD, MPH, vice chair of the AAP’s 2021-2022 Committee on Infectious Diseases and a coauthor of the statement, told this news organization. “But that is really only relevant for children living in endemic areas, primarily Puerto Rico but some other smaller U.S .territories as well.”

Dengue fever also is endemic in American Samoa and the U.S. Virgin Islands.

Notably, a new section has been added on routine recommendations for use of the Dengvaxia vaccine.

The 2022 policy statement addresses regular immunization of children from birth to 18 years and catch-up vaccination for those aged 4 months to 18 years. In addition to the AAP, multiple complementary physician and nurse organizations have approved the updates. The ACIP schedule is revised annually to reflect current recommendations on vaccines licensed by the U.S. Food and Drug Administration.

Most of the other changes this year involve minor updates to clarify language or improve usability. “CDC and AAP are always working to make the schedule as user-friendly as possible, with improvements made every year,” Dr. O’Leary, professor of pediatric infectious diseases at the University of Colorado at Denver, Aurora, said.

In terms of physician acceptance, he added, “I don’t think any of the changes would be considered controversial.”

Among other updates and clarifications:

• For Haemophilus influenzae type b (Hib) vaccination, the text now includes recommendations for the hexavalent Vaxelis vaccine (diphtheria, tetanus, pertussis, polio, Hib, and hepatitis B) for both routine and catch-up vaccination.
• For hepatitis A, the relevant note has been updated to clarify the age for routine vaccination.
• For human papillomavirus (HPV), the note now clarifies when an HPV series is complete with no additional dose recommended.
• The special situations section has been amended to specify which persons with immunocompromising conditions such as HIV should receive three doses of HPV vaccine regardless of age at initial vaccination.
• For measles, mumps, and rubella, routine vaccination now includes recommendations on the combination measles, mumps, rubella, and varicella vaccine.
• For meningococcal serogroup A, C, W, and Y vaccines, the augmented text explains when these can be simultaneously administered with serogroup B meningococcal vaccines, preferably at different anatomic sites. The language for the dosing schedule for Menveo vaccination in infants also has been clarified.
• In the catch-up immunization schedule for late-starting children aged 4 months to 18 years, the text on Hib has been changed so that the minimum interval between dose two and dose three now refers to Vaxelis, while reference to the discontinued Comvax (Hib-Hep B) vaccine has been removed.

As in other years, graphic changes have been made to table coloration and layout to improve accessibility. And as before, the 2022 childhood and adolescent immunization schedule has been updated to ensure consistency between its format and that of the 2022 adult immunization schedules.

The AAP committee stressed that clinically significant adverse events after immunization should be reported to the Vaccine Adverse Event Reporting System.

The full 2022 schedule can be found on the CDC’s website.

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

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

It’s a matter of quality, not quantity. That’s the gist of a new Israeli study that shows that unvaccinated people with a prior SARS-CoV-2 infection create antibodies that are more effective in the long run compared with others who were vaccinated but never infected.

“While the quantity of antibodies decreases with time in both COVID-19 recovered patients and vaccinated individuals, the quality of antibody performance increases following infection but not after vaccination,” lead author Carmit Cohen, PhD, said in an interview.

This difference could explain why previously infected patients appear to be better protected against a new infection than those who have only been vaccinated, according to a news release attached to the research.

One key caveat: This research does not include people from the later part of the pandemic.

This means there is a catch in terms of timing, William Schaffner, MD, Vanderbilt University School of Medicine, Nashville, Tenn., said when asked to comment on the study: “The study involved only the early COVID strains – it has no information on either the Delta or Omicron variants. Thus, the results primarily are of scientific or historical interest but are not immediately relevant to the current situation.”

The findings come from an early release of a study to be presented at the European Congress of Clinical Microbiology & Infectious Diseases in April.

An unexpected finding of the study showed that obese people had better protection – a higher and more sustained immune response – compared with overweight and normal-weight individuals.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” Dr. Schaffner said. “Obesity does predispose to more severe disease.”
 

A focus on earlier strains

Dr. Cohen – a senior research assistant in infectious disease prevention at the Sheba Medical Center in Ramat Gan, Israel – and her colleagues recruited participants between March 25, 2020 and Nov. 25, 2020 and completed analysis in April 2021. This means they assessed people with a history of infection from the original, the Alpha, and some Beta strains of SARS-CoV-2.

Dr. Cohen indicated that the next phase of their research will examine innate and acquired immune responses to the more recent Delta and Omicron variants.

The investigators analyzed the antibody-induced immune response up to 1 year in 130 COVID-19 recovered but unvaccinated individuals versus up to 8 months among 402 others matched by age and body mass index (BMI) and without previous infection who received two doses of the Pfizer vaccine.

The numbers of antibodies a month after vaccination were higher than those in the COVID-19 recovered patients. However, these numbers also declined more steeply in the vaccinated group, they note.

To assess the antibody performance, the investigators used the avidity index. This assay measures antibody function based on the strength of the interactions between the antibody and the viral antigen.

They found that the avidity index was higher in vaccinated individuals than in recovered patients initially but changes over time. At up to 6 months, the index did not significantly change in vaccinated individuals, whereas it gradually increased in recovered patients. This increase would potentially protect them from reinfection, the authors note.

These findings stand in stark contrast to an Oct. 29, 2021, Centers for Disease Control and Prevention study that found that COVID-19 vaccines provided five times the protection of natural immunity.

Those results, published in the organization’s Morbidity and Mortality Weekly Report, suggest that vaccination helps people mount a higher, stronger, and more consistent level of immunity against COVID-19 hospitalization than infection alone for at least 6 months.
 

Protection linked to obesity

Another finding that ran against the scientific grain was the data about obesity.

There was a higher and more persistent antibody performance among people with a BMI of 30 kg/m².

This could relate to greater disease severity and/or a more pronounced initial response to infection among the obese group.

“Our hypothesis is that patients with obesity begin with a more pronounced response – reflected also by the disease manifestation – and the trend of decline is similar, therefore the kinetics of immune response remain higher throughout the study,” Dr. Cohen said.

“The results in the obese group were indeed unexpected and need further research to confirm or dispute,” said Dr. Schaffner, who is also the current medical director of the National Foundation for Infectious Diseases. “Obesity does predispose to more severe disease.”
 

Before the boosters

Along with using participants from only the earlier part of the pandemic, another limitation of the study was that the vaccinated group had only two doses of vaccine; boosters were not given during the time of the study, Dr. Schaffner said.

“Again, not the current situation.”

“That said, the strength and duration of natural immunity provided by the early variants was solid for up to a year, confirming previous reports,” he said.

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

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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

In a first, a middle-aged woman has been in remission from HIV for 14 months after being treated for leukemia with transplants of adult stem cells and umbilical cord blood. If she remains off treatment without any hint of HIV, she would be only the third person in the world – after the Berlin Patient and the London Patient – to be cured through a transplant.

“Her own virus could not infect her cells,” said Yvonne Bryson, MD, chief of pediatric infectious diseases at the University of California, Los Angeles, who presented the study at the Conference on Retroviruses and Opportunistic Infections, which both presenters and the audience attended remotely.

The middle-aged New York woman of mixed race, who has asked that her specific race and age not be shared to protect her privacy, was diagnosed with HIV in 2013 when she was still in the very early stages of infection. She started treatment immediately and quickly achieved an undetectable viral load. An undetectable viral load not only prevents someone from transmitting HIV to others but also reduces or eliminates HIV replication, which means fewer variants and less time for the virus to infiltrate cells where it can hide.

But in 2017, she was diagnosed with leukemia. As a last resort to cure her of the cancer, she received a combination of adult stem cells from a relative’s blood that closely matched her own and umbilical cord blood obtained from a cord blood bank. That particular sample of cord blood was selected for its genetic mutation against the CCR5 receptor on immune cells, CD4 T cells. That mutation makes the immune system resistant to HIV.

The two previous HIV cures, of Berlin Patient Timothy Ray Brown and London Patient Adam Castillejo, also used stem cell transplantation with a CCR5 mutation, but theirs were bone marrow transplants. Bone marrow transplants are more arduous than cord blood transplants, which are commonly used in pediatric cancer treatment.

In this case, the physicians treating her used both.

“This allows the adult cells to accelerate and grow up until the cord blood takes over,” said Dr. Bryson. During her presentation, Dr. Bryson pointed to two types of data: First, she presented data showing the level of HIV in the patient’s blood. Soon after HIV diagnosis and treatment, her viral load dropped to undetectable levels. She had a spike of virus when she received the transplant, but then it went back to undetectable and has stayed that way ever since.

Meanwhile, following the transplant, her immune system started rebuilding itself using the new, HIV-resistant cells provided in the transplant. As her care team watched, no graft-versus-host (GVH) disease, a common side effect of stem cell transplants, emerged. In fact, the transplant went so well that she was discharged early from the hospital.

One hundred days after the transplant, the immune system contained within the cord blood had taken over. Her CD4 immune cells returned to normal levels a little more than a year after the transplant. By 27 months, she decided to stop all HIV treatment to see if the transplant had worked.

This was the real test. But as Dr. Bryson and colleagues continued to watch her HIV viral load and her CD4 counts and search for infectious virus, they didn’t find any. She tested negative for HIV by antibody test. Dr. Bryson grew 75 million of her cells in a lab to look for any HIV. None. Aside from one blip in detectable HIV DNA at 14 weeks, researchers never found HIV in the patient again.

“Her cells are resistant to HIV now – both her own strains and laboratory strains,” Dr. Bryson told this news organization. “It’s been 14 months since then. She has no rebound and no detectable virus.”

The presentation drew as raucous as praise gets in a virtual environment. The comments began pouring in.

“Impressive results,” wrote Jim Hoxie, MD, professor emeritus at the University of Pennsylvania, Philadelphia.

“Exciting case,” wrote Allison Agwu, MD, a professor of pediatrics at Johns Hopkins University, Baltimore.

And Dennis Copertino, a research specialist at Weill Cornell Medicine, New York, wrote: “Thank you so much for translating this important cure strategy to people of color.”

Most donors with CCR5 mutations are White, Dr. Bryson said, suggesting that this approach, in a mixed-race woman, could expand the pool of people living with HIV and cancer who are good candidates for the approach.

But other observers had questions, ones that may require more research to answer. Some asked why this woman’s virus, after transplantation, wasn’t just immune to viruses with CCR5 but also another variant, called CXCR4, that one wouldn’t expect. Luis Montaner, DVM, director of the Immunopathogenesis Laboratory at the Wistar Institute in Philadelphia, wondered whether it was more than the blood that had cleared HIV. Did it get into the tissue, too? That question has not yet been answered.

For Carl Dieffenbach, PhD, director of the division of AIDS at the National Institute of Allergy and Infectious Diseases, the lack of GVH disease was a powerful and hopeful finding.

“There’s been this ongoing hypothesis that maybe graft-versus-host disease was needed at some level to help clear out every last single CD4+ T cell that may or may not have been harboring replication-competent virus,” Dr. Dieffenbach said in an interview. “But there was no GVH disease. That’s incredible. It’s a wonderful thing.”

Now the challenge is to move from a single case to making cure available to other people living with HIV.

The case also got cure researchers thinking.

Dr. Montaner called the case “an encouraging roadmap supporting anti-CCR5 strategies by CRISPR Cas9,” studies that are now underway.

Steven Deeks, MD, called the case “perhaps a model for how we might do this using a person’s own cells. Because we were never really going to be transplanting cells from another person as a scalable cure.”

For people living with HIV, particularly women of color, the results raise hopes and questions. Nina Martinez knows something about being a “first.” In 2019, she was the first American woman of color living with HIV to donate a kidney to another person living with the virus. To her, the excitement over the first woman of color being cured of HIV just shines a light on how very White and male HIV cure studies have been until now.

“For me, I’m not looking for a cure in which the successful step forward is me getting cancer,” she said in an interview. “I’m looking at, what’s going to be sustainable? I want to know what’s going to work for a group of people.”

Gina Marie Brown, a social worker living with HIV in New Orleans, is also thinking of groups of people.

“Every time we get a breakthrough, it’s like the sun is taken from behind the clouds a little more,” said Ms. Brown. “I think about people in the South, who bear a huge burden of HIV. I think about trans women. I think about Black women, and gay, bisexual, and same-gender-loving men. This could really impact HIV – in the same way that PrEP [pre-exposure prophylaxis] has, the same way that one pill once a day has.”

When Ms. Brown was diagnosed with HIV 22 years ago, she started to plan her funeral.

“That’s how much I thought HIV was a death sentence,” she told this news organization. “Oh my goodness! Glad you stuck around, Gina.”

The study was funded by the National Institutes of Health. Dr. Bryson, Dr. Dieffenbach, Dr. Deeks, and Dr. Montaner disclosed no relevant financial relationships.

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

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

Many factors influence a child’s subsequent susceptibility to respiratory tract infection (RTI), including breastfeeding, crowded conditions, and exposure to environmental tobacco. Now researchers have found that asymptomatic viral infection in the first days of a baby’s life are linked to a greater risk of respiratory infections in later life.

The new research, published in Nature Microbiology, was conducted as part of the Microbiome Utrecht Infant Study (MUIS), a healthy infant birth cohort study that’s been running for 6 years.

In their study, the authors explained how the respiratory tract is “populated by a specialized microbial ecosystem, which is seeded during and directly following birth,” adding that, “despite recognition of many host and environmental factors known to modulate RTI susceptibility, the mechanism by which a child develops recurrent or severe RTIs, while others remain healthy, remains largely unknown”.

Researchers from the University of Edinburgh and University Medical Centre Utrecht (the Netherlands) examined nasal mucosa samples of 114 babies at various times from birth until 12 months of age. They then analyzed the gene activity of the babies’ nasal mucosa, the microbes present in the lining of the nose, and any viruses that infected the children.
 

Interferon-related mucosal gene activity

The researchers described how the microbiome – the community of microbes in the body – of a newborn baby can be influenced by many things, including delivery method, breastfeeding, antibiotics and the hospital environment. They highlighted how viruses were found to interact with a newborn’s immune system and microbiome in a way that affected both a child’s risk, and number, of subsequent infections.

They explained how when a viral infection was detected in the first days after birth, which they said largely occurred asymptomatically, specific mucosal genes were activated – genes involved with interferons – coinciding with a change in the composition of the microbiome, promoting the growth of potentially harmful microbes.

“The interferon-related gene activity caused by an early first viral infection is thought to create a proinflammatory environment that makes babies susceptible to future infections,” they said, adding that in their study they have demonstrated that “first asymptomatic viral encounters were associated with increased interferon signaling, and preceded the development of disadvantageous respiratory microbiota profiles and clinical RTIs”.
 

Proinflammatory and microbiologically perturbed environment

Debby Bogaert, PhD, chair of paediatric medicine at the University of Edinburgh, said: “We were surprised to see viral infections occur so early in life, and go mostly unnoticed, probably because the infant’s immune system is in what is known as a state of tolerance after birth. Despite this, these infections seem to affect a normal immune development, which is important to know.”

The authors wrote that their data supports the hypothesis that first viral encounters trigger an interferon-associated proinflammatory environment, which then further drives airway inflammation and symptomatology in a “self-enforcing positive feedback loop”. They said that this “proinflammatory and microbiologically perturbed environment in turn renders an individual more vulnerable to recurrent viral-induced RTIs”.

Wouter de Steenhuijsen, PhD, postdoctoral investigator at University Medical Centre Utrecht, said: “Although further work will be needed to confirm the causality of our findings, the data from this study indicate that early-life encounters with respiratory viruses – especially during the first days of life – may set the tone for subsequent non-beneficial host-microbe interactions, which are related to an infection risk and possibly long term respiratory health.”

Dr. Bogaert added: “Only from birth onwards will an infant start to develop its microbiome. Limiting the number of viral encounters in those first days to weeks of life might be essential for a healthy immune and microbiome development, and consequently long term respiratory health.”

A version of this article first appeared on Medscape UK.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

A deep molecular dive into COVID-19 patients found that the presence of autoantibodies in peripheral blood at initial diagnosis was the chief of four risk factors predicting if a patient would experience long COVID.

Other significant early predictors of prolonged COVID symptoms – which the researchers called postacute sequelae – were having type 2 diabetes, SARS-CoV-2 RNAemia, and Epstein-Barr virus (EBV) viremia, Yapeng Su, PhD, of the Institute for Systems Biology (ISB) in Seattle, and colleagues wrote in Cell.

Having EBV viremia suggested that latent EBV has been reactivated, the authors noted.

“The most important postacute sequelae [that is conditions that are consequences of a disease] of COVID is the presence of autoantibodies,” James R. Heath, PhD, president of ISB and a bioengineering professor at the University of Washington, Seattle, said in an interview. “It’s about two times more important than the others.”

Dr. Heath and coauthors said early detection of this and other variables could prompt earlier aggressive treatment in patients susceptible to long COVID and ward off lingering symptoms.

“These predictive measures of long COVID can also help to better inform patients of their possible disease course,” study coauthor Daniel G. Chen, an undergraduate researcher at ISB, said in an interview. “We were also able to partially resolve the immunological underpinnings of some postacute sequelae of COVID in a way that suggested potential therapies, and the timing of those therapies.”

For example, he continued, the use of antivirals very early in the infectious course may mitigate the later development of long COVID. “This will, of course, have to be explored in an appropriately designed clinical trial.

“We also identified biomarkers of certain types of long COVID, such as neurological sequelae. Those biomarkers can help define the condition, which is a first step towards developing treatments.”

Study findings

With COVID patients monitored for 2 or 3 months, the study findings of the international “multiomic profiling” analysis include:

• Subclinical patient autoantibodies that reduce anti–SARS-CoV-2 antibodies suggest there is immune dysregulation during COVID-19 infection.
• Reactivation of latent other viruses during initial infection may be contributing to long COVID.
• Gastrointestinal postacute sequelae of COVID presents with a unique postacute expansion of cytotoxic T cells.
• SARS-CoV-2–specific and cytomegalovirus-specific CD8+ T cells displayed unique dynamics during recovery from infection.

According to the authors, as many as 69% of COVID-19 patients suffer from long COVID – a range of new, recurrent, or ongoing problems 4 or more weeks following initial SARS-CoV-2 infection. These may include memory loss, gastrointestinal distress, fatigue, anosmia, and shortness of breath.

Long COVID has been associated with acute disease severity, and is suspected to be related to autoimmune factors and unresolved viral fragments, according to the paper.
 

Research methods

The international study did a deep and detailed dive into multiple molecular markers of long COVID. It enrolled 209 COVID-19 patients with varying degrees of disease severity and matched them to 457 healthy controls. The researchers’ goal was to identify discrete and quantifiable long COVID factors and guide possible preemptive treatment. 

Patients were assessed at three time points: at initial diagnosis, during the acute disease phase about a week later, and again 2 to 3 months post onset of symptoms after recovery from the acute phase of COVID. At the third assessment, some patients had lingering symptoms such as fatigue (52% ), cough (25%), and loss of taste or sense of smell (18%).

Blood draws were analyzed for autoantibodies and SARS-CoV-2–specific antibodies, global plasma proteomic and metabolomic profiles, and single-cell multiomic characterizations of peripheral blood mononuclear cells.

Each blood draw was paired with nasal-swab and plasma measurements of SARS-CoV-2 viral load and the data sets were integrated with electronic health records and self-reported patient symptoms to guide the interpretation of the molecular signatures of long COVID.
 

Author conclusions

The authors found an association between T2 hyperinflammation and long COVID–anticipating autoantibodies. This association further implies that hyperinflammation-controlling therapies in the acute stage of COVID may influence whether a patient experiences long COVID. “However, the detailed timing and context of these therapies matter, and, thus, future well-controlled studies will be needed to test these and other therapeutic implications,” Dr. Su and colleagues wrote.

Moreover, the negative correlations between anti–SARS-CoV-2 IgG and certain autoantibodies may suggest that patients with elevated autoantibody levels are more susceptible to breakthrough infections, the authors said.

“Many patients with high autoantibodies simultaneously have low protective antibodies that neutralize SARS-CoV-2, and that’s going to make them more susceptible to breakthrough infections,” Mr. Chen explained.*

“Detectability of most [long COVID-19 factors] at COVID diagnosis emphasizes the importance of early disease measurements for understanding emergent chronic conditions and suggests [long COVID] treatment strategies,” they wrote.

According to Mr. Chen, there are clear similarities in underlying immunobiology between patients with COVID autoantibodies and patients with systemic lupus erythematosus.

“These findings are also helping us frame our thinking around other chronic autoimmune conditions, such as postacute Lyme syndrome, for example,” said Dr. Heath.

The bottom line, said Mr. Chen, is that measuring early long COVID indicators may result in preventive treatments. “An example is the cortisol deficiency we see in certain long COVID patients. There are known treatments such as cortisol replacement therapy that should be explored for this group.”

Outside expert’s take on findings

Commenting on the study, Sherry Hsiang-Yi Chou, MD, who was not involved in the research, called the study a very important first step in understanding the path of this complex phenomenon and perhaps other conditions with long-term side effects.

“The researchers have done huge amount of innovative scientific work. They’ve shown the DNA signature of how our bodies respond to this disease,” said Dr. Chou, who is chief of the division of neurocritical care at Northwestern Medicine in Chicago.

“This type of research will help us scientifically understand and differentiate the various syndromes within long COVID. It will help identify who’s at risk for different aspects of this syndrome and lead to following them for longer periods in clinical trials,” she added.

The authors acknowledged that lengthier studies in larger cohorts were needed to see which patients will develop long-term chronic postacute sequelae of COVID.

This research was supported by the Wilke Family Foundation, the Parker Institute for Cancer Immunotherapy, Merck, and the Biomedical Advanced Research and Development Authority. Other support came from the National Institutes of Health, the Bill and Melinda Gates Foundation, Saint John’s Cancer Center, Fred Hutchinson Cancer Research Center, and the European Union’s Horizon 2020 research and innovation program. Dr. Heath is a cofounder of Pact Pharma. He and several coauthors disclosed various ties to multiple private-sector companies. Mr. Chen and Dr. Chou had no competing interests.

*Correction, 1/28: An earlier version of this story misidentified Daniel G. Chen, an undergraduate researcher at ISB.

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

In a large, blinded study of peanut-allergic toddlers published in The Lancet, 71% of treated participants could safely consume 5,000 mg of peanut protein – equivalent to nearly 17 peanuts – after 2½ years on oral immunotherapy. Even after stopping maintenance dosing for the next 6 months, more than 1 in 5 maintained that level of protection, and nearly 3 in 5 still met the 600-mg benchmark (about 2 peanuts) set by the phase 3 PALISADE trial of the FDA-approved peanut-flour product, Palforzia.

About 2% of children in the United States are allergic to peanuts, and most will not outgrow this allergy. In addition, other research suggests that the immune system is more malleable during early childhood.

Consistent with this idea, prior research showed that toddlers can succeed with peanut oral immunotherapy (OIT) – a regimen that builds tolerance through small amounts of the allergen consumed daily for months. However, that trial (DEVIL) was small, was conducted at a single site, and had no placebo group.

In contrast, the Peanut Oral Immunotherapy in Children Trial (IMPACT) enrolled 146 children aged 1-3 years at five academic medical centers in the United States – the first placebo-controlled study of OIT in this younger age group.

“This is a well done study,” Jaclyn Bjelac, MD, associate director of the Food Allergy Center of Excellence at the Cleveland Clinic, told this news organization. “We have seen improved outcomes in OIT, both in our own experience and other published studies, so while this is no surprise, the outcomes and large number of participants contribute to this being a really exciting publication.”

The trial was long and demanding for families. Toddlers who reacted to 500 mg or less of peanut protein in an entry food challenge were randomized in a 2:1 ratio to receive daily peanut flour or oat flour placebo. After initial dose escalation (from 0.1 mg to 6 mg) and biweekly buildup to a 2,000-mg target dose by week 30, participants continued with 20,00-mg daily maintenance dosing through week 134 – at which point they underwent a food challenge. They then went off treatment for 26 weeks and had another food challenge (week 160). In addition, participants came in for skin-prick and blood tests at baseline and at weeks 30, 82, 134, and 160.

In the placebo group, only 23 of 50 participants (46%) completed the study. “If you did 2½ years of this and then bombed the food challenge, you probably can guess that you were not on the real thing. And they were still asked to come back in 6 months and do it again. So, sure enough, a big chunk of those people chose not to continue, and you can’t blame them,” said Lancet co-author Edwin Kim, MD, in an interview. Dr. Kim directs the UNC Food Allergy Initiative at the University of North Carolina School of Medicine, Chapel Hill.

There was attrition in the treatment group as well. Among 96 children initially assigned to this arm, 68 (71%) passed the 5,000-mg peanut challenge at week 134 – but 11 withdrew in the study’s off-treatment phase. “It was a very tough decision. How much do you give toward science?” said Dr. Kim. “When push came to shove, some of the families couldn’t pull the trigger to potentially give up what they worked so hard for.”

In the intention-to-treat analysis, 20 of 96 treated participants (21%) could still tolerate 5,000 mg of peanut protein after going off therapy for 6 months. That translates to a 29% remission rate in the per-protocol subset (n = 70) who completed the study. Forty (57%) of these completers safely consumed at least 1,755 mg of peanut (cumulative dose). By comparison, the PALISADE trial of Palforzia used a 10,430-mg cumulative peanut dose to measure treatment efficacy.

On safety, 98% of treated participants – but also 80% of the placebo group – reported reactions, of which 35 were treated with epinephrine in 21 children receiving peanut OIT.

While some have noted that epinephrine use seemed high, Dr. Kim said, “we’re actually OK with that, because we’d much rather they overtreat and make sure that 1-year-old is safe than take any chances.” Overall, the safety profile looks similar to prior OIT studies of older children. “I think it suggests that, yeah, side effects will happen, [but] they’re all manageable, and people are not anaphylaxing left and right.”

On remission and immunologic parameters, benefits seemed stronger in the youngest subset (12 to 24 months), particularly those with lower peanut-specific IgE at baseline. These trends require further analyses, though, given the limited number of participants under 24 months.

Another noteworthy observation from longitudinal peanut-specific IgE trends in the placebo group: “Avoidance may not be benign,” Dr. Kim said. “If you look at their labs, they don’t stay flat. They actually go up.” The results jibe with the long-held idea of an early window of opportunity while a child’s immune system is maturing. “If you can grab this kid when his IgE is 10, versus next year when it might be 50, maybe you’ll get a different treatment effect,” Dr. Kim said. “We don’t know that for sure, but the placebo labs kind of point toward that.”

Beyond the science, there are practical advantages to starting OIT early. “Trying to convince a 9-year-old who’s been petrified of peanuts for their whole life to start doing this every day is not an easy task,” whereas with a 1- or 2-year-old, “you build it into their routine,” Dr. Kim said.

Plus, some say there’s no need for families to wait for regulatory approval of additional commercial products for very young children. Though some have advocated against the use of “grocery store” products, most peanut OIT research “has used the same 12% light roast defatted peanut flour used in IMPACT,” noted Marcus S. Shaker, MD, professor of pediatrics and of medicine at the Dartmouth Geisel School of Medicine and a physician at the Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire. The commercial product (Palforzia) and grocery-store products “come from the exact same source in the U.S.,” he said in an interview. “Both are an option for parents to consider, but a commercial product is not, nor has [it] ever been, a necessity.”

Dr. Bjelac reports no relevant financial relationships. Dr. Kim reports consultancy with Aimmune Therapeutics, Allako, AllerGenis, Belhaven Pharma, DBV Technologies, Duke Clinical Research Institute, and Nutricia; advisory board membership with ALK, DBV Technologies, Kenota Health, and Ukko; and grant support from the NIH’s National Institute of Allergy and Infectious Diseases, National Center for Complementary and Integrative Health and Immune Tolerance Network, Food Allergy Research and Education, and the Wallace Research Foundation. Dr. Shaker has participated in research funded by DBV, is cochair of the AAAAI/ACAAI Joint Task Force on Practice Parameters, is an associate editor at the Annals of Allergy, Asthma, and Immunology, and is an editorial board member of the Journal of Allergy and Clinical Immunology in Practice.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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

Epstein-Barr virus (EBV) is the likely cause of multiple sclerosis (MS), new research confirms. Investigators found the risk of MS increased 32-fold following EBV infection.

This study is the first to provide compelling evidence of a causal link between EBV and MS, principal investigator Alberto Ascherio, MD, DrPH, professor of epidemiology, Harvard T. H. Chan School of Public Health, and professor of medicine, Harvard Medical School, Boston, told this news organization.

The “prevailing” view has been that MS is “an autoimmune disease of unknown etiology,” said Dr. Ascherio. “Now we know MS is a complication of a viral infection.” With this knowledge, he added, “we can redirect research” to find antiviral drugs to treat the disease.

The study was published online Jan. 13 in Science.
 

Unique dataset

A chronic disease of the central nervous system, MS involves an inflammatory attack on the myelin sheath and the axons it insulates. The disease affects 2.8 million people worldwide.

EBV is a human herpesvirus that can cause infectious mononucleosis. After infection, it persists in latent form in B-lymphocytes.

EBV is common and infects about 95% of adults. Most individuals are already infected with the virus by age 18 or 20 years, making it difficult to study uninfected populations, said Dr. Ascherio.

However, access to a “huge” database of more than 10 million active-duty U.S. service personnel made this possible, he said.

Service members are screened for HIV at the start of their service care and biennially thereafter. The investigators used stored blood samples to determine the relation between EBV infection and MS over a 20-year period from 1993 to 2013.

Researchers examined 801 MS case patients and 1,566 matched controls without MS. Most individuals were under 20 at the time of their first blood collection. Symptom onset for those who developed MS was a median of 10 years after the first sample was obtained.

Only one of the 801 MS case patients had no serologic evidence of EBV. This individual may have been infected with the virus after the last blood collection, failed to seroconvert in response to infection, or was misdiagnosed, the investigators note.

The hazard ratio for MS between EBV seroconversion versus persistent EBV seronegative was 32.4 (95% CI, 4.3-245.3; P < .001).
 

An MS vaccine?

MS risk was not increased after infection with cytomegalovirus, a herpesvirus that is transmitted through saliva, as is EBV.

Researchers measured serum concentrations of neurofilament light chain (sNflL), a biomarker of neuroaxonal degeneration, in samples from EBV-negative individuals at baseline. There were no signs of neuroaxonal degeneration before EBV seroconversion in subjects who later developed MS.

This indicates that “EBV infection preceded not only symptom onset but also the time of the first detectable pathological mechanisms underlying MS,” the investigators note.

The very magnitude of increased MS risk of MS observed EBV almost completely rules out confounding by known risk factors. Smoking and vitamin D deficiency double the risk, and genetic predisposition and childhood obesity also only raise the risks of MS to a “moderate” degree, said Dr. Ascherio.

It’s not clear why only some people infected with EBV go on to develop MS, he said.

The idea that reverse causation – that immune dysregulation during the preclinical phase of MS increases susceptibility to EBV infection – is unlikely, the investigators note. For instance, EBV seroconversion occurs before elevation of sNfL levels, an early marker of preclinical MS.

Since most MS cases appear to be caused by EBV, a suitable vaccine might thwart the disease. “A vaccine could, in theory, prevent infection and prevent MS,” said Dr. Ascherio, adding that there’s ongoing work to develop such a vaccine.

Another approach is to target the virus driving MS disease progression. Developing appropriate antivirals might treat and even cure MS, said Dr. Ascherio.
 

‘Compelling data’

In an accompanying commentary, William H. Robinson, MD, PhD, professor, Division of Immunology and Rheumatology, department of medicine, Stanford (Calif.) University, and a colleague said the study findings “provide compelling data that implicate EBV as the trigger for the development of MS.”

The mechanism or mechanisms by which EBV leads to MS “remain elusive,” the commentary authors write.

“Possibilities include molecular mimicry, through which EBV viral protein sequences mimic human myelin proteins and other CNS proteins and thereby induce autoimmunity against myelin and CNS antigens,” they note.

As other factors, including genetic susceptibility, are important to MS, EBV infection is likely necessary but not sufficient to trigger MS, said the commentary. “Infection with EBV is the initial pathogenic step in MS, but additional fuses must be ignited for the full pathophysiology.”

The commentary authors query whether there may be “new opportunities” for therapy with vaccines or antivirals. “Now that the initial trigger for MS has been identified, perhaps MS could be eradicated.”

In a statement from the Science Media Center, an independent venture promoting views from the scientific community, two other experts offered their take on the study.

Paul Farrell, PhD, professor of tumor virology, Imperial College London, said the paper “provides very clear confirmation of a causal role for EBV in most cases of MS.”

While there’s evidence that a vaccine can prevent the EBV disease infectious mononucleosis, no vaccine candidate has yet prevented the virus from infecting and establishing long-term persistence in people, noted Dr. Farrell.

“So, at this stage it is not clear whether a vaccine of the types currently being developed would be able to prevent the long-term effects of EBV in MS,” he said.

Daniel Davis, PhD, professor of immunology, University of Manchester, United Kingdom, commented that the value of this new discovery is not an immediate medical cure or treatment but is “a major step forward” in understanding MS.

The study “sets up new research working out the precise details of how this virus can sometimes lead to an autoimmune disease,” said Dr. Davis. “There is no shortage of ideas in how this might happen in principle and hopefully the correct details will emerge soon.”

The study received funding from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, National Multiple Sclerosis Society, the German Research Foundation, the National Institutes of Health, and the Howard Hughes Medical Institute. Dr. Ascherio reports no relevant financial relaitonships. Dr. Robinson is a coinventor on a patent application filed by Stanford University that includes antibodies to EBV. Dr. Farrell reports serving on an ad hoc review panel for GSK on EBV vaccines in 2019 as a one off. He has a current grant from MRC on EBV biology, including some EBV sequence variation, but the grant is not about MS. Dr. Davis reports no relevant financial relationships.

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