MDedge Infectious Disease

Cardiac injury caused by COVID-19 may be much less common than suggested previously, a new study has found.

The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.

“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.

They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”

The study was published online in JACC: Cardiovascular Imaging.

Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.

“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.

However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.

To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.

The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.

“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.

Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.

Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.

However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.

Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.

Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.

“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.

“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.

Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.

He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.

However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.

“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.

“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.

“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.

“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.

Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.

“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”

This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.

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

Cardiac injury caused by COVID-19 may be much less common than suggested previously, a new study has found.

The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.

“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.

They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”

The study was published online in JACC: Cardiovascular Imaging.

Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.

“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.

However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.

To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.

The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.

“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.

Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.

Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.

However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.

Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.

Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.

“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.

“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.

Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.

He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.

However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.

“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.

“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.

“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.

“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.

Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.

“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”

This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.

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

Cardiac injury caused by COVID-19 may be much less common than suggested previously, a new study has found.

The study examined cardiac MRI scans in 31 patients before and after having COVID-19 infection and found no new evidence of myocardial injury in the post-COVID scans relative to the pre-COVID scans.

“To the best of our knowledge this is the first cardiac MRI study to assess myocardial injury pre- and post-COVID-19,” the authors stated.

They say that while this study cannot rule out the possibility of rare events of COVID-19–induced myocardial injury, “the complete absence of de novo late gadolinium enhancement lesions after COVID-19 in this cohort indicates that outside special circumstances, COVID-19–induced myocardial injury may be much less common than suggested by previous studies.”

The study was published online in JACC: Cardiovascular Imaging.

Coauthor Till F. Althoff, MD, Cardiovascular Institute, Clínic–University Hospital Barcelona, said in an interview that previous reports have found a high rate of cardiac lesions in patients undergoing imaging after having had COVID-19 infection.

“In some reports, this has been as high as 80% of patients even though they have not had severe COVID disease. These reports have been interpreted as showing the majority of patients have some COVID-induced cardiac damage, which is an alarming message,” he commented.

However, he pointed out that the patients in these reports did not undergo a cardiac MRI scan before they had COVID-19 so it wasn’t known whether these cardiac lesions were present before infection or not.

To try and gain more accurate information, the current study examined cardiac MRI scans in the same patients before and after they had COVID-19.

The researchers, from an arrhythmia unit, made use of the fact that all their patients have cardiac MRI data, so they used their large registry of patients in whom cardiac MRI had been performed, and cross referenced this to a health care database to identify those patients who had confirmed COVID-19 after they obtaining a cardiac scan at the arrhythmia unit. They then conducted another cardiac MRI scan in the 31 patients identified a median of 5 months after their COVID-19 infection.

“These 31 patients had a cardiac MRI scan pre-COVID and post COVID using exactly the same scanner with identical sequences, so the scans were absolutely comparable,” Dr. Althoff noted.

Of these 31 patients, 7 had been hospitalized at the time of acute presentation with COVID-19, of whom 2 required intensive care. Most patients (29) had been symptomatic, but none reported cardiac symptoms.

Results showed that, on the post–COVID-19 scan, late gadolinium enhancement lesions indicative of residual myocardial injury were encountered in 15 of the 31 patients (48%), which the researchers said is in line with previous reports.

However, intraindividual comparison with the pre–COVID-19 cardiac MRI scans showed all these lesions were preexisting with identical localization, pattern, and transmural distribution, and thus not COVID-19 related.

Quantitative analyses, performed independently, detected no increase in the size of individual lesions nor in the global left ventricular late gadolinium enhancement extent.

Comparison of pre- and post COVID-19 imaging sequences did not show any differences in ventricular functional or structural parameters.

“While this study only has 31 patients, the fact that we are conducting intra-individual comparisons, which rules out bias, means that we don’t need a large number of patients for reliable results,” Dr. Althoff said.

“These types of lesions are normal to see. We know that individuals without cardiac disease have these types of lesions, and they are not necessarily an indication of any specific pathology. I was kind of surprised by the interpretation of previous data, which is why we did the current study,” he added.

Dr. Althoff acknowledged that some cardiac injury may have been seen if much larger numbers of patients had been included. “But I think we can say from this data that COVID-induced cardiac damage is much less of an issue than we may have previously thought,” he added.

He also noted that most of the patients in this study had mild COVID-19, so the results cannot be extrapolated to severe COVID-19 infection.

However, Dr. Althoff pointed out that all the patients already had atrial fibrillation, so would have been at higher risk of cardiac injury from COVID-19.

“These patients had preexisting cardiac risk factors, and thus they would have been more susceptible to both a more severe course of COVID and an increased risk of myocardial damage due to COVID. The fact that we don’t find any myocardial injury due to COVID in this group is even more reassuring. The general population will be at even lower risk,” he commented.

“I think we can say that, in COVID patients who do not have any cardiac symptoms, our study suggests that the incidence of cardiac injury is very low,” Dr. Althoff said.

“Even in patients with severe COVID and myocardial involvement reflected by increased troponin levels, I wouldn’t be sure that they have any residual cardiac injury. While it has been reported that cardiac lesions have been found in such patients, pre-COVID MRI scans were not available so we don’t know if they were there before,” he added.

“We do not know the true incidence of cardiac injury after COVID, but I think we can say from this data that it is definitely not anywhere near the 40%-50% or even greater that some of the previous reports have suggested,” he stated.

Dr. Althoff suggested that, based on these data, some of the recommendations based on previous reports such the need for follow-up cardiac scans and caution about partaking in sports again after COVID-19 infection, are probably not necessary.

“Our data suggest that these concerns are unfounded, and we need to step back a bit and stop alarming patients about the risk of cardiac damage after COVID,” he said. “Yes, if patients have cardiac symptoms during or after COVID infection they should get checked out, but I do not think we need to do a cardiac risk assessment in patients without cardiac symptoms in COVID.”

This work is supported in part by grants from Instituto de Salud Carlos III, the Spanish government, Madrid, and Fundació la Marató de TV3 in Catalonia. Dr. Althoff has received research grants for investigator-initiated trials from Biosense Webster.

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

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

The Ohio measles outbreak continues to expand, with cases now totaling 81 – a 37% increase in the course of just 2 weeks.

The lead health official where the outbreak is occurring said the driving force behind the spread is vaccine hesitancy. Most of the children infected were unvaccinated but were old enough to get the measles, mumps, and rubella (MMR) shot, which is 97% effective at preventing measles.

“I think these are individuals who are making a decision not to protect their children against vaccine-preventable diseases, and some of them are making a specific decision not to use the MMR vaccine,” Columbus Public Health Commissioner Mysheika W. Roberts, MD, told JAMA.

She said that parents’ refusal to vaccinate their children was due to a misconception that the vaccine causes autism.

“We’re sounding the alarm that if your child is of age and not vaccinated, they should get vaccinated ASAP,” Dr. Roberts said, noting that she hasn’t seen that happening more.

Health officials have predicted the outbreak, which started in November, will last at least several months. Measles is so contagious that 9 out of 10 unvaccinated people in a room will become infected if exposed.

All of the infections have been in children. According to the Columbus Public Health measles dashboard, of the 81 confirmed cases:

• 29 children have been hospitalized.
• 22 cases are among children under 1 year old.
• No deaths have been reported.

Dr. Roberts said the hospitalized children have had symptoms including dehydration, diarrhea, and pneumonia. Some have had to go to the intensive care unit.

Measles infection causes a rash and a fever that can spike beyond 104° F. Sometimes, the illness can lead to brain swelling, brain damage, and even death, the CDC says.

One of the most recent cases was an infant too young to be vaccinated who lives 45 miles away from where the outbreak began, the Dayton Daily News reported. That’s the first case in Clark County in more than 20 years. At least 10% of kindergartners’ parents in the region’s elementary schools opted out of vaccines because of religious or moral objections.

“We knew this was coming. It was a matter of when, not if,” Yamini Teegala, MD, chief medical officer at Rocking Horse Community Health Center in Springfield, told the Dayton Daily News.

This is the second measles outbreak this year. Minnesota tallied 22 cases since June in an unrelated outbreak, JAMA reported.

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

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

New COVID-19 cases in children jumped by 66% during the first 2 weeks of December after an 8-week steady period lasting through October and November, according to the American Academy of Pediatrics and the Children’s Hospital Association.

New cases reached close to 48,000 for the most recent reporting week, Dec. 9-15, after rising to just over 41,000 the previous week and totaling less than 29,000 for the week of Nov. 25 to Dec. 1. That increase of almost 19,000 cases is the largest over a 2-week period since late July, the AAP and CHA said in their weekly COVID report based on data collected from state and territorial health department websites.

[This publication has been following the AAP/CHA report since the summer of 2020 and continues to share the data for the sake of consistency, but it must be noted that a number of states are no longer updating their public COVID dashboards. As a result, there is now a considerable discrepancy between the AAP/CHA weekly figures and those reported by the Centers for Disease Control and Prevention, which has no such limitations on state data.]

The situation involving new cases over the last 2 weeks is quite different from the CDC’s perspective. The agency does not publish a weekly count, instead offering cumulative cases, which stood at almost 16.1 million as of Dec. 14. Calculating a 2-week total puts the new-case count for Dec. 1-14 at 113,572 among children aged 0-17 years. That is higher than the AAP/CHA count (88,629) for roughly the same period, but it is actually lower than the CDC’s figure (161,832) for the last 2 weeks of November.

The CDC data, in other words, suggest that new cases have gone down in the last 2 weeks, while the AAP and CHA, with their somewhat limited perspective, announced that new cases have gone up.

One COVID-related measure from the CDC that is not contradicted by other sources is hospitalization rates, which had climbed from 0.16 new admissions in children aged 0-17 years with confirmed COVID per 100,000 population on Oct. 22 to 0.29 per 100,000 on Dec. 9. Visits to the emergency department with diagnosed COVID, meanwhile, have been fairly steady so far through December in children, according to the CDC.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

An investigational vaccine against respiratory syncytial virus (RSV) in pregnant women has been shown to help protect infants against severe disease, according to the vaccine’s manufacturer.

Pfizer recently announced that in the course of a randomized, double-blind, placebo-controlled phase 3 study, the vaccine RSVpreF had an almost 82% efficacy against severe RSV infection in infants from birth through the first 90 days of life, according to a company press release.

The vaccine also had a 69% efficacy against severe disease through the first 6 months of life. A total of 7,400 women had received a single dose of 120 mcg RSVpreF in the late second or third trimester of their pregnancy. There were no signs of safety issues for the mothers or infants.

Due to the good results, the enrollment in the study was halted on the recommendation of the study’s Data Monitoring Committee after achieving a primary endpoint. The company plans to apply for marketing authorization to the U.S. Food and Drug Administration by the end of 2022 and to other regulatory agencies in 2023.

“The directness of the strategy, to vaccinate expectant mothers during pregnancy so that their newborn is then later protected, is new and a very interesting approach,” commented Prof. Ortwin Adams, MD, head of virologic diagnostics at the Institute for Virology of the University Hospital of Düsseldorf (Germany) to the Science Media Centre (SMC).

In terms of the RSV vaccination strategy presented, “the unborn child has taken center stage from the outset.” Because the vaccination route is the placental transfer of antibodies from mother to child (“passive immunity”), “... the medical points of contact for this vaccination will be the gynecologists, not the pediatricians,” Dr. Adams said.

“This concept imitates the natural process, since the mother normally passes immune defenses she acquired through infections to the child via the umbilical cord and her breast milk before and after birth. This procedure is long-proven and practiced worldwide, especially in nonindustrialized countries, for a variety of diseases, including tetanus, whooping cough (pertussis), and viral flu (influenza),” explained Markus Rose, MD, PhD, head of Pediatric Pulmonology at the Olgahospital, Stuttgart, Germany.

The development of an RSV vaccine had ground to a halt for many decades: A tragedy in the 1960s set the whole field of research back. Using the model of the first polio vaccine, scientists had manufactured an experimental vaccine with inactivated viruses. However, tests showed that the vaccine did not protect the children vaccinated, but it actually infected them with RSV, they then fell ill, and two children died. Today, potential RSV vaccines are first tested on adults and not on children.
 

Few treatment options

RSV causes seasonal epidemics, can lead to bronchiolitis and pneumonia in infants, and is one of the main causes of hospital stays in young children. Monoclonal antibodies are currently the only preventive option, since there is still no vaccine. Usually, 60%-70% of infants and nearly all children younger than 2 years are infected with RSV, but the virus can also trigger pneumonia in adults.

“RSV infections constitute a major public health challenge: It is the most dangerous respiratory virus for young infants, it is also a threat to the chronically ill and immunocompromised of all ages, and [it] is the second most common cause of death worldwide (after malaria) in young children,” stated Dr. Rose.

Recently, pandemic-related measures (face masks, more intense disinfection) meant that the “normal” RSV infections in healthy adults, which usually progress like a mild cold, were prevented, and mothers were unable to pass on as much RSV immune defense to their children. “This was presumably responsible in part for the massive wave of RSV infections in fall and winter of 2021/22,” explained Dr. Rose.

Thomas Mertens, MD, PhD, chair of the Standing Committee on Vaccination at the Robert Koch Institute (STIKO) and former director of the Institute for Virology at Ulm University Hospital, Germany, also noted: “It would be an important and potentially achievable goal to significantly reduce the incidence rate of hospitalizations. In this respect, RSV poses a significant problem for young children, their parents, and the burden on pediatric clinics.”
 

Final evaluation pending

“I am definitely finding the data interesting, but the original data are needed,” Dr. Mertens said. Once the data are published at a conference or published in a peer-reviewed journal, physicians will be able to better judge the data for themselves, he said.

Dr. Rose characterized the new vaccine as “novel,” including in terms of its composition. Earlier RSV vaccines used the so-called postfusion F protein as their starting point. But it has become known in the meantime that the key to immunogenicity is the continued prefusion state of the apical epitope: Prefusion F-specific memory B cells in adults naturally infected with RSV produce potent neutralizing antibodies.

The new vaccine is bivalent and protects against both RSV A and RSV B.

To date, RSV vaccination directly in young infants have had only had a weak efficacy and were sometimes poorly tolerated. The vaccine presented here is expected to be tested in young adults first, then in school children, then young children.

Through successful vaccination of the entire population, the transfer of RS viruses to young children could be prevented. “To what extent this, or any other RSV vaccine still to be developed on the same basis, will also be effective and well tolerated in young infants is still difficult to assess,” said Dr. Rose.

Dr. Mertens emphasized that all of the study data now needs to be seen as quickly as possible: “This is also a general requirement for transparency from the pharmaceutical companies, which is also rightly criticized.”

This article was originally published in Medscape’s German edition and a version appeared on Medscape.com.

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

A systematic review of observational studies and clinical trials found dolutegravir and raltegravir to be safe and effective for treating teens and children living with HIV.

Effectiveness was higher across dolutegravir studies, the authors reported. After 12 months of treatment and observation, viral suppression levels were greater than 70% in most studies assessing dolutegravir. Viral suppression with raltegravir after 12 months varied between 42% and 83%.

“Our findings support the use of these two integrase inhibitors as part of WHO-recommended regimens for treating HIV,” said lead study author Claire Townsend, PhD, an epidemiologist and consultant to the World Health Organization HIV department in Geneva. “They were in line with what has been reported in adults and provide reassurance for the continued use of these two drugs in children and adolescents.”

The study was published in the Journal of the International AIDS Society.
 

Tracking outcomes for WHO guidelines

Integrase inhibitors, including dolutegravir and raltegravir, have become leading first- and second-line treatments in patients with HIV, largely owing to their effectiveness and fewer side effects, compared with other antiretroviral treatments.

Monitoring short- and long-term health outcomes of these widely used drugs is critical, the authors wrote. This is especially the case for dolutegravir, which has recently been approved in pediatric formulations. The review supported the development of the 2021 WHO consolidated HIV guidelines.

Dr. Townsend and colleagues searched the literature and screened trial registries for relevant studies conducted from January 2009 to March 2021. Among more than 4,000 published papers and abstracts, they identified 19 studies that met their review criteria relating to dolutegravir or raltegravir in children or adolescents aged 0-19 years who are living with HIV, including two studies that reported data on both agents.

Data on dolutegravir were extracted from 11 studies that included 2,330 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 9 cohort studies. Data on raltegravir were extracted from 10 studies that included 649 children and adolescents in 1 randomized controlled trial, 1 single-arm trial, and 8 cohort studies.

The median follow-up in the dolutegravir studies was 6-36 months. Six studies recruited participants from Europe, three studies were based in sub-Saharan Africa, and two studies included persons from multiple geographic regions.

Across all studies, grade 3/4 adverse events were reported in 0%-50% of cases. Of these adverse events, very few were drug related, and no deaths were attributed to either dolutegravir or raltegravir.

However, Dr. Townsend cautioned that future research is needed to fill in evidence gaps “on longer-term safety and effectiveness of dolutegravir and raltegravir in children and adolescents,” including “research into adverse outcomes such as weight gain, potential metabolic changes, and neuropsychiatric adverse events, which have been reported in adults.”

The researchers noted that the small sample size of many of the studies contributed to variability in the findings and that most studies were observational, providing important real-world data but making their results less robust compared with data from randomized controlled studies with large sample sizes. They also noted that there was a high risk of bias (4 studies) and unclear risk of bias (5 studies) among the 15 observational studies included in their analysis.

“This research is particularly important because it supports the WHO recommendation that dolutegravir, which has a particularly high barrier of resistance to the HIV virus, be synchronized in adults and children as the preferred first-line and second-line treatment against HIV,” said Natella Rakhmanina, MD, PhD, director of HIV Services & Special Immunology at the Children’s National Hospital in Washington, D.C. Dr. Rakhmanina was not associated with the study.

Dr. Rakhmanina agreed that the safety profile of both drugs is “very good.” The lack of serious adverse events was meaningful, she highlighted, because “good tolerability is very important, particularly in children” as it means that drug compliance and viral suppression are achievable.

Two authors reported their authorship on two studies included in the review, as well as grant funding from ViiV Healthcare/GlaxoSmithKline, the marketing authorization holder for dolutegravir.

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

Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

Two years ago, when the first COVID-19 vaccines were administered, marked a game-changing moment in the fight against the pandemic. But it also was a significant moment for messenger RNA (mRNA) technology, which up until then had shown promise but had never quite broken through. 

Now, scientists hope to use this technology to develop more vaccines, with those at the University of Pennsylvania hoping to use that technology to pioneer yet another first: a universal flu vaccine that can protect us against all flu types, not just a select few. 

It’s the latest advance in a new age of vaccinology, where vaccines are easier and faster to produce, as well as more flexible and customizable. 

“It’s all about covering the different flavors of flu in a way the current vaccines cannot do,” says Ofer Levy, MD, PhD, director of the Precision Vaccines Program at Boston Children’s Hospital, who is not involved with the UPenn research. “The mRNA platform is attractive here given its scalability and modularity, where you can mix and match different mRNAs.” 

A recent paper, published in Science, reports successful animal tests of the experimental vaccine, which, like the Pfizer-BioNTech and Moderna COVID vaccines, relies on mRNA. But the idea is not to replace the annual flu shot. It’s to develop a primer that could be administered in childhood, readying the body’s B cells and T cells to react quickly if faced with a flu virus. 

It’s all part of a National Institutes of Health–funded effort to develop a universal flu vaccine, with hopes of heading off future flu pandemics. Annual shots protect against flu subtypes known to spread in humans. But many subtypes circulate in animals, like birds and pigs, and occasionally jump to humans, causing pandemics. 

“The current vaccines provide very little protection against these other subtypes,” says lead study author Scott Hensley, PhD, a professor of microbiology at UPenn. “We set out to make a vaccine that would provide some level of immunity against essentially every influenza subtype we know about.” 

That’s 20 subtypes altogether. The unique properties of mRNA vaccines make immune responses against all those antigens possible, Dr. Hensley says. 

Old-school vaccines introduce a weakened or dead bacteria or virus into the body, but mRNA vaccines use mRNA encoded with a protein from the virus. That’s the “spike” protein for COVID, and for the experimental vaccine, it’s hemagglutinin, the major protein found on the surface of all flu viruses.

Mice and ferrets that had never been exposed to the flu were given the vaccine and produced high levels of antibodies against all 20 flu subtypes. Vaccinated mice exposed to the exact strains in the vaccine stayed pretty healthy, while those exposed to strains not found in the vaccine got sick but recovered quickly and survived. Unvaccinated mice exposed to the flu strain died. 

The vaccine seems to be able to “induce broad immunity against all the different influenza subtypes,” Dr. Hensley says, preventing severe illness if not infection overall. 

Still, whether it could truly stave off a pandemic that hasn’t happened yet is hard to say, Dr. Levy cautions. 

“We are going to need to better learn the molecular rules by which these vaccines protect,” he says.

But the UPenn team is forging ahead, with plans to test their vaccine in human adults in 2023 to determine safety, dosing, and antibody response.

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

The percentage of people in the U.S. getting the latest COVID-19 booster shot has crept up by single digits in the past couple months, despite health officials pleading for people to do so before the Christmas holiday. 

Now, a new poll shows why so few people are willing to roll up their sleeves again.

The most common reasons people give for not getting the latest booster shot is that they “don’t think they need one” (44%) and they “don’t think the benefits are worth it” (37%), according to poll results from the Kaiser Family Foundation. 

The data comes amid announcements by the Centers for Disease Control and Prevention that boosters reduced COVID-19 hospitalizations by up to 57% for U.S. adults and by up to 84% for people age 65 and older. Those figures are just the latest in a mountain of research reporting the public health benefits of COVID-19 vaccines.

Despite all of the statistical data, health officials’ recent vaccination campaigns have proven far from compelling. 

So far, just 15% of people age 12 and older have gotten the latest booster, and 36% of people age 65 and older have gotten it, the CDC’s vaccination trackershows.

Since the start of the pandemic, 1.1 million people in the U.S. have died from COVID-19, with the number of deaths currently rising by 400 per day, The New York Times COVID tracker shows.

Many experts continue to note the need for everyone to get booster shots regularly, but some advocate that perhaps a change in strategy is in order.

“What the administration should do is push for vaccinating people in high-risk groups, including those who are older, those who are immunocompromised and those who have comorbidities,” Paul Offitt, MD, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told CNN.

Federal regulators have announced they will meet Jan. 26 with a panel of vaccine advisors to examine the current recommended vaccination schedule as well as look at the effectiveness and composition of current vaccines and boosters, with an eye toward the make-up of next-generation shots.

Vaccines are the “best available protection” against hospitalization and death caused by COVID-19, said Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, in a statement announcing the planned meeting.

“Since the initial authorizations of these vaccines, we have learned that protection wanes over time, especially as the virus rapidly mutates and new variants and subvariants emerge,” he said. “Therefore, it’s important to continue discussions about the optimal composition of COVID-19 vaccines for primary and booster vaccination, as well as the optimal interval for booster vaccination.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

It’s a story perhaps more appropriate for Halloween than for the festive holiday season, given its scary implications. Four Omicron subvariants of the virus that causes COVID-19 will be the most common strains going from person to person in the winter of 2022-2023, new research predicts.

Not too dire so far, until the researchers’ other findings are considered.

The BQ.1, BQ1.1, XBB, and XBB.1 subvariants are the most resistant to neutralizing antibodies, researcher Qian Wang, PhD, and colleagues wrote in a study published online in the journal Cell. This means people have no or “markedly reduced” protection against infection from these four strains, even if they’ve already had COVID-19 or are vaccinated and boosted multiple times, including with a bivalent vaccine.

On top of that, all available monoclonal antibody treatments are mostly or completely ineffective against these subvariants.

What does that mean for the immediate future? The findings are definitely “worrisome,” said Eric Topol, MD, founder and director of the Scripps Translational Research Institute in La Jolla, Calif.

But evidence from other countries, specifically Singapore and France, show that at least two of these variants turned out not to be as damaging as expected, likely because of high numbers of people vaccinated or who survived previous infections, he said.

Still, there is little to celebrate in the new findings, except that COVID-19 vaccinations and prior infections can still reduce the risk for serious outcomes such as hospitalization and death, the researchers wrote.

In fact, Centers for Disease Control and Prevention data released on Dec. 16 shows that people who have received four shots of the original COVID-19 vaccines as well as the bivalent booster were 57% less likely to visit an urgent care clinic or emergency room, regardless of age. 

It comes at a time when BQ.1 and BQ.1.1 account for about 70% of the circulating variants, data show. In addition, hospitalizations are up 18% over the past 2 weeks and COVID-19 deaths are up 50% nationwide, The New York Times reported.

Globally, in many places, an “immunity wall” that has been built, Dr. Topol said. That may not be the case in the United States.  

“The problem in the United States, making it harder to predict, is that we have a very low rate of recent boosters, in the past 6 months, especially in seniors,” he said. For example, only 36% of Americans aged 65 years and older, the group with highest risk, have received an updated bivalent booster.
 

An evolving virus

The subvariants are successfully replacing BA.5, which reigned as one of the most common Omicron variants over the past year. The latest CDC data show that BA.5 now accounts for only about 10% of the circulating virus. The researchers wrote: “This rapid replacement of virus strains is raising the specter of yet another wave of infections in the coming months.”

BQ.1 and BQ.1.1 evolved directly from BA.5 – adding more and some novel mutations to the SARS-CoV-2 virus. XBB and XBB.1 are the “offspring” of a combination of two other strains, known as BJ.1 and BA.2.75.

The story sounds familiar to the researchers. “The rapid rise of these subvariants and their extensive array of spike mutations are reminiscent of the appearance of the first Omicron variant last year, thus raising concerns that they may further compromise the efficacy of current COVID-19 vaccines and monoclonal antibody therapeutics,” they wrote. “We now report findings that indicate that such concerns are, sadly, justified, especially so for the XBB and XBB.1 subvariants.”

To figure out how effective existing antibodies could be against these newer subvariants, Dr. Wang and colleagues used blood samples from five groups of people. They tested serum from people who had three doses of the original COVID-19 vaccine, four doses of the original vaccine, those who received a bivalent booster, people who experienced a breakthrough infection with the BA.2 Omicron variant, and those who had a breakthrough with a BA.4 or BA.5 variant.

Adding the new subvariants to these serum samples revealed that the existing antibodies in the blood were ineffective at wiping out or neutralizing BQ.1, BQ.1.1, XBB, and XBB.1.

The BQ.1 subvariant was six times more resistant to antibodies than BA.5, its parent strain, and XBB.1 was 63 times more resistant compared with its predecessor, BA.2.

This shift in the ability of vaccines to stop the subvariants “is particularly concerning,” the researchers wrote.
 

Wiping out treatments too

Dr. Wang and colleagues also tested how well a panel of 23 different monoclonal antibody drugs might work against the four subvariants. The therapies all worked well against the original Omicron variant and included some approved for use through the Food and Drug Administration emergency use authorization (EUA) program at the time of the study.

They found that 19 of these 23 monoclonal antibodies lost effectiveness “greatly or completely” against XBB and XBB.1, for example.

This is not the first time that monoclonal antibody therapies have gone from effective to ineffective. Previous variants have come out that no longer responded to treatment with bamlanivimab, etesevimab, imdevimab, casirivimab, tixagevimab, cilgavimab, and sotrovimab. Bebtelovimab now joins this list and is no longer available from Eli Lilly under EUA because of this lack of effectiveness.

The lack of an effective monoclonal antibody treatment “poses a serious problem for millions of immunocompromised individuals who do not respond robustly to COVID-19 vaccines,” the researchers wrote, adding that “the urgent need to develop active monoclonal antibodies for clinical use is obvious.”

A limitation of the study is that the work is done in blood samples. The effectiveness of COVID-19 vaccination against the BQ and XBB subvariants should be evaluated in people in clinical studies, the authors noted.

Also, the current study looked at how well antibodies could neutralize the viral strains, but future research, they added, should look at how well “cellular immunity” or other aspects of the immune system might protect people.

Going forward, the challenge remains to develop vaccines and treatments that offer broad protection as the coronavirus continues to evolve.

In an alarming ending, the researchers wrote: “We have collectively chased after SARS-CoV-2 variants for over 2 years, and yet, the virus continues to evolve and evade.”

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

PARIS – To date, studies of antibiotic course length for treating urinary tract infections in men have been patchy and retrospective.

Through recent randomized trials, guidelines can now be based on more solid data.

In sum, to maximize clinical and microbiologic success, a nonfebrile urinary tract infection is treated for 7 days, and a febrile urinary tract infection is treated for a minimum of 14 days.

At the 116th conference of the French urology association, Matthieu Lafaurie, MD, of the Multidisciplinary Infectious Diseases Unit U21, Saint Louis Hospital, Paris, reviewed the literature on this subject.
 

Guidelines for men

The European Association of Urology made its position clear in a text updated in 2022. It stated: “Cystitis in men that does not affect the prostate is rare and should be classed as a complicated infection. Therefore, treatment with antimicrobial drugs that penetrate the prostate tissue is needed in men presenting with symptoms of a urinary tract infection.” In its classification of prostatitis, the National Institutes of Health distinguishes between acute prostatitis (symptoms of a urinary tract infection; stage I) and chronic prostatitis (recurrent infection with the same microorganism; stage II).

Although the French-language Society of Infectious Diseases distinguishes between febrile and nonfebrile urinary tract infections in males, the academic body does not take into account whether the patient has a fever when determining which antibiotic should be given and how long the course should be: A minimum of 14 days’ treatment is recommended when opting for fluoroquinolones, trimethoprim-sulfamethoxazole (cotrimoxazole), or injectable beta-lactam antibiotics, and at least 21 days is recommended for other drugs or in cases in which there is an underlying urologic condition that has not been treated.

Yet the EAU recommends treating cystitis with antibiotics for at least 7 days, preferably with cotrimoxazole or fluoroquinolone, depending on the results of sensitivity testing. For acute prostatitis, the length of treatment with fluoroquinolones should be at least 14 days.
 

Nonfebrile infections

Participation of men in studies of the treatment of complicated cystitis is variable; at most only 10% of patients in such trials are men. There are few data specific to men with nonfebrile urinary tract infections, and most studies are retrospective and involve small cohorts. One of these is a community-based study that involved 422 men aged 18-104 years who presented with nonfebrile urinary tract infection (acute dysuria, frequency of urination and/or urgency of urination, temperature < 38° C, no general symptoms). Antibiotic treatment was prescribed in 60% of cases. In more than 55% of cases, the length of the course of treatment was 1–7 days. Treatment was with cotrimoxazole, quinolones, and nitrofurantoin.

Another observational retrospective study showed benefit with nitrofurantoin (50 mg/8 h in 94% of cases; 69 patients) and pivmecillinam (200 mg/8 h in 65% of cases; 200 mg/12 h in 30% of patients; 57 patients) in treating lower urinary tract infections in men. The median treatment duration was 7 days. The failure rate was 1.4% and 12%, respectively, for these treatments. Compared to the so-called gold-standard treatment, trimethoprim (10 days/800 mg/12 h; 45 patients), the recurrence rate was 11% and 26% for nitrofurantoin and pivmecillinam versus 7% for trimethoprim. The most significant relapse rate with pivmecillinam was when treatment was given for fewer than 7 days.

This is the only risk factor for further antibiotic treatment and/or recurrence. There was no significant difference between the three drugs with regard to other parameters (urinary tract infection symptoms, benign prostatic hypertrophy, prostate cancer, gram-positive bacteria, etc).

Another retrospective, European study of nitrofurantoin that was published in 2015 included 485 patients (100 mg twice daily in 71% of cases). Clinical cure was defined as an absence of signs or symptoms of a urinary tract infection for 14 days after stopping nitrofurantoin, without use of other antibiotics. The cure rate was 77%. Better efficacy was achieved for patients with gram-negative (vs. gram-positive) bacteria. The treatment duration did not differ significantly (clinical success was achieved when the treatment was taken for 8.6 ± 3.6 days; clinical failure occurred when the treatment was taken for 9.3 ± 6.9 days; P = .28).

Regarding pivmecillinam, a retrospective 2010-2016 study involved 21,864 adults and included 2,524 men who had been treated empirically with pivmecillinam (400 mg three times daily) for significant bacteriuria (Escherichia coli) and a lower urinary tract infection. The researchers concluded that for men, the success rate was identical whether the treatment lasted 5 or 7 days.

An American community-based (urologists, primary care physicians, general medicine services) retrospective cohort study involving 573 men with nonfebrile lower urinary tract infections was conducted from 2011 to 2015. The patients received antibiotic treatment with fluoroquinolones (69.7%), cotrimoxazole (21.2%), nitrofurantoin (5.3%), trimethoprim, beta-lactam antibiotics, or aminoglycosides. No clinical advantage was seen in treating men with urinary tract infections for longer than 7 days.

There are some data on the use of fosfomycin. In an observational retrospective study, 25 men of 52 male adults with leukocyturia and E. coli greater than 105, ESBL, were treated with fosfomycin trometamol 3 g on days 1, 3, 5. Clinical and microbiologic success was achieved for 94% and 78.5%, respectively. No distinction was made between the sexes.

These results were confirmed in a retrospective, observational study involving 18 men (of a total of 75 adults) with no fever or hyperleukocytosis who received the same fosfomycin trometamol regimen. The rate of clinical cure or sterile urine microscopy and culture was 69% at 13 days. The risk failure factor was, as expected, infection with Klebsiella pneumoniae, which was slightly susceptible to fosfomycin, unlike E. coli.

The most recent study in this field was published in 2021. It was also the first randomized, double-blind, placebo-controlled study. In all, 272 men older than 18 years were prescribed either ciprofloxacin or cotrimoxazole for 7-14 days to treat a nonfebrile urinary tract infection. To be eligible for the trial, patients were required to have disease of new onset with at least one of the following symptoms: dysuria, frequency of urination, urgency of urination, hematuria, costovertebral angle tenderness, or perineal, flank, or suprapubic pain. Urine microscopy and culture were not necessary; the approach was wholly symptomatic. Treatment was prescribed for 7 days. Patients were randomly allocated on day 8 to receive treatment for the following 7 days (molecule or placebo). The primary outcome was resolution of clinical symptoms of urinary tract infection by 14 days after completion of active antibiotic treatment. In an intention-to-treat or per-protocol analysis, the difference in efficacy between the two molecules was largely below the required 10%. The treatment duration noninferiority margin was 7 days, compared with 14 days.

“In 2022, with regard to the duration of treatment of nonfebrile urinary tract infections in men, the not completely irrefutable evidence does, however, stack up in favor of the possibility of a 7-day or even 5-day course,” pointed out Dr. Lafaurie. “Fluoroquinolones [such as] ofloxacin, levofloxacin, ciprofloxacin, as well as cotrimoxazole and other antibiotics, such as pivmecillinam, nitrofurantoin, or fosfomycin trometamol, can be used, despite the fact that they pass less easily into the prostate – a not-so-obvious benefit.”
 

Febrile infections

In terms of febrile urinary tract infections, a single-center, prospective, open-label study from 2003 involved 72 male inpatients who were randomly to receive treatment either for 2 weeks or 4 weeks. Treatment consisted of ciprofloxacin 500 mg twice daily. This study provided most of the evidence to justify the recommended 14-day antibiotic course.

Another noninferiority, randomized, placebo-controlled study published in 2017 compared 7- and 14-day treatment with ciprofloxacin 500 mg to placebo twice per week. In men, 7 days of antibiotic therapy was inferior to 14 days during a short-term follow-up but was not inferior during a longer follow-up.

A decisive study, which is currently in the submission phase, could silence debate. “In our noninferiority, multicenter, randomized, double-blind, placebo-controlled study, we have enrolled 240 men over the age of 18 years with a febrile infection documented by a fever of 38° C or more, clinical signs of infection, and leukocyturia at least above 10/mm3 and with symptoms lasting less than 3 months,” said Dr. Lafaurie, the trial coordinator.

The primary outcome for efficacy was microbiologic and clinical success after 6 weeks. Patients received either ofloxacin, ceftriaxone, or cefotaxime (two third-generation cephalosporins in the beta-lactam family).

“We clearly show that, for a 7-day course, the clinical success rate is 55.7%, and for a 14-day course, this goes up to 77.6%, with no difference in terms of adverse effects or selection of resistant bacteria. The predictive factors for success are a 14-day treatment and being under the age of 50 years,” said Dr. Lafaurie.

“Unlike nonfebrile urinary tract infections in men, a 7-day course is insufficient for patients with febrile urinary tract infections, and a minimum of 14 days is required to achieve clinical and microbiological success,” he concluded.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

PARIS – To date, studies of antibiotic course length for treating urinary tract infections in men have been patchy and retrospective.

Through recent randomized trials, guidelines can now be based on more solid data.

In sum, to maximize clinical and microbiologic success, a nonfebrile urinary tract infection is treated for 7 days, and a febrile urinary tract infection is treated for a minimum of 14 days.

At the 116th conference of the French urology association, Matthieu Lafaurie, MD, of the Multidisciplinary Infectious Diseases Unit U21, Saint Louis Hospital, Paris, reviewed the literature on this subject.
 

Guidelines for men

The European Association of Urology made its position clear in a text updated in 2022. It stated: “Cystitis in men that does not affect the prostate is rare and should be classed as a complicated infection. Therefore, treatment with antimicrobial drugs that penetrate the prostate tissue is needed in men presenting with symptoms of a urinary tract infection.” In its classification of prostatitis, the National Institutes of Health distinguishes between acute prostatitis (symptoms of a urinary tract infection; stage I) and chronic prostatitis (recurrent infection with the same microorganism; stage II).

Although the French-language Society of Infectious Diseases distinguishes between febrile and nonfebrile urinary tract infections in males, the academic body does not take into account whether the patient has a fever when determining which antibiotic should be given and how long the course should be: A minimum of 14 days’ treatment is recommended when opting for fluoroquinolones, trimethoprim-sulfamethoxazole (cotrimoxazole), or injectable beta-lactam antibiotics, and at least 21 days is recommended for other drugs or in cases in which there is an underlying urologic condition that has not been treated.

Yet the EAU recommends treating cystitis with antibiotics for at least 7 days, preferably with cotrimoxazole or fluoroquinolone, depending on the results of sensitivity testing. For acute prostatitis, the length of treatment with fluoroquinolones should be at least 14 days.
 

Nonfebrile infections

Participation of men in studies of the treatment of complicated cystitis is variable; at most only 10% of patients in such trials are men. There are few data specific to men with nonfebrile urinary tract infections, and most studies are retrospective and involve small cohorts. One of these is a community-based study that involved 422 men aged 18-104 years who presented with nonfebrile urinary tract infection (acute dysuria, frequency of urination and/or urgency of urination, temperature < 38° C, no general symptoms). Antibiotic treatment was prescribed in 60% of cases. In more than 55% of cases, the length of the course of treatment was 1–7 days. Treatment was with cotrimoxazole, quinolones, and nitrofurantoin.

Another observational retrospective study showed benefit with nitrofurantoin (50 mg/8 h in 94% of cases; 69 patients) and pivmecillinam (200 mg/8 h in 65% of cases; 200 mg/12 h in 30% of patients; 57 patients) in treating lower urinary tract infections in men. The median treatment duration was 7 days. The failure rate was 1.4% and 12%, respectively, for these treatments. Compared to the so-called gold-standard treatment, trimethoprim (10 days/800 mg/12 h; 45 patients), the recurrence rate was 11% and 26% for nitrofurantoin and pivmecillinam versus 7% for trimethoprim. The most significant relapse rate with pivmecillinam was when treatment was given for fewer than 7 days.

This is the only risk factor for further antibiotic treatment and/or recurrence. There was no significant difference between the three drugs with regard to other parameters (urinary tract infection symptoms, benign prostatic hypertrophy, prostate cancer, gram-positive bacteria, etc).

Another retrospective, European study of nitrofurantoin that was published in 2015 included 485 patients (100 mg twice daily in 71% of cases). Clinical cure was defined as an absence of signs or symptoms of a urinary tract infection for 14 days after stopping nitrofurantoin, without use of other antibiotics. The cure rate was 77%. Better efficacy was achieved for patients with gram-negative (vs. gram-positive) bacteria. The treatment duration did not differ significantly (clinical success was achieved when the treatment was taken for 8.6 ± 3.6 days; clinical failure occurred when the treatment was taken for 9.3 ± 6.9 days; P = .28).

Regarding pivmecillinam, a retrospective 2010-2016 study involved 21,864 adults and included 2,524 men who had been treated empirically with pivmecillinam (400 mg three times daily) for significant bacteriuria (Escherichia coli) and a lower urinary tract infection. The researchers concluded that for men, the success rate was identical whether the treatment lasted 5 or 7 days.

An American community-based (urologists, primary care physicians, general medicine services) retrospective cohort study involving 573 men with nonfebrile lower urinary tract infections was conducted from 2011 to 2015. The patients received antibiotic treatment with fluoroquinolones (69.7%), cotrimoxazole (21.2%), nitrofurantoin (5.3%), trimethoprim, beta-lactam antibiotics, or aminoglycosides. No clinical advantage was seen in treating men with urinary tract infections for longer than 7 days.

There are some data on the use of fosfomycin. In an observational retrospective study, 25 men of 52 male adults with leukocyturia and E. coli greater than 105, ESBL, were treated with fosfomycin trometamol 3 g on days 1, 3, 5. Clinical and microbiologic success was achieved for 94% and 78.5%, respectively. No distinction was made between the sexes.

These results were confirmed in a retrospective, observational study involving 18 men (of a total of 75 adults) with no fever or hyperleukocytosis who received the same fosfomycin trometamol regimen. The rate of clinical cure or sterile urine microscopy and culture was 69% at 13 days. The risk failure factor was, as expected, infection with Klebsiella pneumoniae, which was slightly susceptible to fosfomycin, unlike E. coli.

The most recent study in this field was published in 2021. It was also the first randomized, double-blind, placebo-controlled study. In all, 272 men older than 18 years were prescribed either ciprofloxacin or cotrimoxazole for 7-14 days to treat a nonfebrile urinary tract infection. To be eligible for the trial, patients were required to have disease of new onset with at least one of the following symptoms: dysuria, frequency of urination, urgency of urination, hematuria, costovertebral angle tenderness, or perineal, flank, or suprapubic pain. Urine microscopy and culture were not necessary; the approach was wholly symptomatic. Treatment was prescribed for 7 days. Patients were randomly allocated on day 8 to receive treatment for the following 7 days (molecule or placebo). The primary outcome was resolution of clinical symptoms of urinary tract infection by 14 days after completion of active antibiotic treatment. In an intention-to-treat or per-protocol analysis, the difference in efficacy between the two molecules was largely below the required 10%. The treatment duration noninferiority margin was 7 days, compared with 14 days.

“In 2022, with regard to the duration of treatment of nonfebrile urinary tract infections in men, the not completely irrefutable evidence does, however, stack up in favor of the possibility of a 7-day or even 5-day course,” pointed out Dr. Lafaurie. “Fluoroquinolones [such as] ofloxacin, levofloxacin, ciprofloxacin, as well as cotrimoxazole and other antibiotics, such as pivmecillinam, nitrofurantoin, or fosfomycin trometamol, can be used, despite the fact that they pass less easily into the prostate – a not-so-obvious benefit.”
 

Febrile infections

In terms of febrile urinary tract infections, a single-center, prospective, open-label study from 2003 involved 72 male inpatients who were randomly to receive treatment either for 2 weeks or 4 weeks. Treatment consisted of ciprofloxacin 500 mg twice daily. This study provided most of the evidence to justify the recommended 14-day antibiotic course.

Another noninferiority, randomized, placebo-controlled study published in 2017 compared 7- and 14-day treatment with ciprofloxacin 500 mg to placebo twice per week. In men, 7 days of antibiotic therapy was inferior to 14 days during a short-term follow-up but was not inferior during a longer follow-up.

A decisive study, which is currently in the submission phase, could silence debate. “In our noninferiority, multicenter, randomized, double-blind, placebo-controlled study, we have enrolled 240 men over the age of 18 years with a febrile infection documented by a fever of 38° C or more, clinical signs of infection, and leukocyturia at least above 10/mm3 and with symptoms lasting less than 3 months,” said Dr. Lafaurie, the trial coordinator.

The primary outcome for efficacy was microbiologic and clinical success after 6 weeks. Patients received either ofloxacin, ceftriaxone, or cefotaxime (two third-generation cephalosporins in the beta-lactam family).

“We clearly show that, for a 7-day course, the clinical success rate is 55.7%, and for a 14-day course, this goes up to 77.6%, with no difference in terms of adverse effects or selection of resistant bacteria. The predictive factors for success are a 14-day treatment and being under the age of 50 years,” said Dr. Lafaurie.

“Unlike nonfebrile urinary tract infections in men, a 7-day course is insufficient for patients with febrile urinary tract infections, and a minimum of 14 days is required to achieve clinical and microbiological success,” he concluded.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

PARIS – To date, studies of antibiotic course length for treating urinary tract infections in men have been patchy and retrospective.

Through recent randomized trials, guidelines can now be based on more solid data.

In sum, to maximize clinical and microbiologic success, a nonfebrile urinary tract infection is treated for 7 days, and a febrile urinary tract infection is treated for a minimum of 14 days.

At the 116th conference of the French urology association, Matthieu Lafaurie, MD, of the Multidisciplinary Infectious Diseases Unit U21, Saint Louis Hospital, Paris, reviewed the literature on this subject.
 

Guidelines for men

The European Association of Urology made its position clear in a text updated in 2022. It stated: “Cystitis in men that does not affect the prostate is rare and should be classed as a complicated infection. Therefore, treatment with antimicrobial drugs that penetrate the prostate tissue is needed in men presenting with symptoms of a urinary tract infection.” In its classification of prostatitis, the National Institutes of Health distinguishes between acute prostatitis (symptoms of a urinary tract infection; stage I) and chronic prostatitis (recurrent infection with the same microorganism; stage II).

Although the French-language Society of Infectious Diseases distinguishes between febrile and nonfebrile urinary tract infections in males, the academic body does not take into account whether the patient has a fever when determining which antibiotic should be given and how long the course should be: A minimum of 14 days’ treatment is recommended when opting for fluoroquinolones, trimethoprim-sulfamethoxazole (cotrimoxazole), or injectable beta-lactam antibiotics, and at least 21 days is recommended for other drugs or in cases in which there is an underlying urologic condition that has not been treated.

Yet the EAU recommends treating cystitis with antibiotics for at least 7 days, preferably with cotrimoxazole or fluoroquinolone, depending on the results of sensitivity testing. For acute prostatitis, the length of treatment with fluoroquinolones should be at least 14 days.
 

Nonfebrile infections

Participation of men in studies of the treatment of complicated cystitis is variable; at most only 10% of patients in such trials are men. There are few data specific to men with nonfebrile urinary tract infections, and most studies are retrospective and involve small cohorts. One of these is a community-based study that involved 422 men aged 18-104 years who presented with nonfebrile urinary tract infection (acute dysuria, frequency of urination and/or urgency of urination, temperature < 38° C, no general symptoms). Antibiotic treatment was prescribed in 60% of cases. In more than 55% of cases, the length of the course of treatment was 1–7 days. Treatment was with cotrimoxazole, quinolones, and nitrofurantoin.

Another observational retrospective study showed benefit with nitrofurantoin (50 mg/8 h in 94% of cases; 69 patients) and pivmecillinam (200 mg/8 h in 65% of cases; 200 mg/12 h in 30% of patients; 57 patients) in treating lower urinary tract infections in men. The median treatment duration was 7 days. The failure rate was 1.4% and 12%, respectively, for these treatments. Compared to the so-called gold-standard treatment, trimethoprim (10 days/800 mg/12 h; 45 patients), the recurrence rate was 11% and 26% for nitrofurantoin and pivmecillinam versus 7% for trimethoprim. The most significant relapse rate with pivmecillinam was when treatment was given for fewer than 7 days.

This is the only risk factor for further antibiotic treatment and/or recurrence. There was no significant difference between the three drugs with regard to other parameters (urinary tract infection symptoms, benign prostatic hypertrophy, prostate cancer, gram-positive bacteria, etc).

Another retrospective, European study of nitrofurantoin that was published in 2015 included 485 patients (100 mg twice daily in 71% of cases). Clinical cure was defined as an absence of signs or symptoms of a urinary tract infection for 14 days after stopping nitrofurantoin, without use of other antibiotics. The cure rate was 77%. Better efficacy was achieved for patients with gram-negative (vs. gram-positive) bacteria. The treatment duration did not differ significantly (clinical success was achieved when the treatment was taken for 8.6 ± 3.6 days; clinical failure occurred when the treatment was taken for 9.3 ± 6.9 days; P = .28).

Regarding pivmecillinam, a retrospective 2010-2016 study involved 21,864 adults and included 2,524 men who had been treated empirically with pivmecillinam (400 mg three times daily) for significant bacteriuria (Escherichia coli) and a lower urinary tract infection. The researchers concluded that for men, the success rate was identical whether the treatment lasted 5 or 7 days.

An American community-based (urologists, primary care physicians, general medicine services) retrospective cohort study involving 573 men with nonfebrile lower urinary tract infections was conducted from 2011 to 2015. The patients received antibiotic treatment with fluoroquinolones (69.7%), cotrimoxazole (21.2%), nitrofurantoin (5.3%), trimethoprim, beta-lactam antibiotics, or aminoglycosides. No clinical advantage was seen in treating men with urinary tract infections for longer than 7 days.

There are some data on the use of fosfomycin. In an observational retrospective study, 25 men of 52 male adults with leukocyturia and E. coli greater than 105, ESBL, were treated with fosfomycin trometamol 3 g on days 1, 3, 5. Clinical and microbiologic success was achieved for 94% and 78.5%, respectively. No distinction was made between the sexes.

These results were confirmed in a retrospective, observational study involving 18 men (of a total of 75 adults) with no fever or hyperleukocytosis who received the same fosfomycin trometamol regimen. The rate of clinical cure or sterile urine microscopy and culture was 69% at 13 days. The risk failure factor was, as expected, infection with Klebsiella pneumoniae, which was slightly susceptible to fosfomycin, unlike E. coli.

The most recent study in this field was published in 2021. It was also the first randomized, double-blind, placebo-controlled study. In all, 272 men older than 18 years were prescribed either ciprofloxacin or cotrimoxazole for 7-14 days to treat a nonfebrile urinary tract infection. To be eligible for the trial, patients were required to have disease of new onset with at least one of the following symptoms: dysuria, frequency of urination, urgency of urination, hematuria, costovertebral angle tenderness, or perineal, flank, or suprapubic pain. Urine microscopy and culture were not necessary; the approach was wholly symptomatic. Treatment was prescribed for 7 days. Patients were randomly allocated on day 8 to receive treatment for the following 7 days (molecule or placebo). The primary outcome was resolution of clinical symptoms of urinary tract infection by 14 days after completion of active antibiotic treatment. In an intention-to-treat or per-protocol analysis, the difference in efficacy between the two molecules was largely below the required 10%. The treatment duration noninferiority margin was 7 days, compared with 14 days.

“In 2022, with regard to the duration of treatment of nonfebrile urinary tract infections in men, the not completely irrefutable evidence does, however, stack up in favor of the possibility of a 7-day or even 5-day course,” pointed out Dr. Lafaurie. “Fluoroquinolones [such as] ofloxacin, levofloxacin, ciprofloxacin, as well as cotrimoxazole and other antibiotics, such as pivmecillinam, nitrofurantoin, or fosfomycin trometamol, can be used, despite the fact that they pass less easily into the prostate – a not-so-obvious benefit.”
 

Febrile infections

In terms of febrile urinary tract infections, a single-center, prospective, open-label study from 2003 involved 72 male inpatients who were randomly to receive treatment either for 2 weeks or 4 weeks. Treatment consisted of ciprofloxacin 500 mg twice daily. This study provided most of the evidence to justify the recommended 14-day antibiotic course.

Another noninferiority, randomized, placebo-controlled study published in 2017 compared 7- and 14-day treatment with ciprofloxacin 500 mg to placebo twice per week. In men, 7 days of antibiotic therapy was inferior to 14 days during a short-term follow-up but was not inferior during a longer follow-up.

A decisive study, which is currently in the submission phase, could silence debate. “In our noninferiority, multicenter, randomized, double-blind, placebo-controlled study, we have enrolled 240 men over the age of 18 years with a febrile infection documented by a fever of 38° C or more, clinical signs of infection, and leukocyturia at least above 10/mm3 and with symptoms lasting less than 3 months,” said Dr. Lafaurie, the trial coordinator.

The primary outcome for efficacy was microbiologic and clinical success after 6 weeks. Patients received either ofloxacin, ceftriaxone, or cefotaxime (two third-generation cephalosporins in the beta-lactam family).

“We clearly show that, for a 7-day course, the clinical success rate is 55.7%, and for a 14-day course, this goes up to 77.6%, with no difference in terms of adverse effects or selection of resistant bacteria. The predictive factors for success are a 14-day treatment and being under the age of 50 years,” said Dr. Lafaurie.

“Unlike nonfebrile urinary tract infections in men, a 7-day course is insufficient for patients with febrile urinary tract infections, and a minimum of 14 days is required to achieve clinical and microbiological success,” he concluded.

This article was translated from the Medscape French edition. A version appeared on Medscape.com.

It’s beginning to look less like an epidemic as seasonal flu activity “appears to be declining in some areas,” according to the Centers for Disease Control and Prevention.

Declines in a few states and territories were enough to lower national activity, as measured by outpatient visits for influenza-like illness, for the second consecutive week. This reduced the weekly number of hospital admissions for the first time in the 2022-2023 season, according to the CDC influenza division’s weekly FluView report.

Flu-related hospital admissions slipped to about 23,500 during the week of Dec. 4-10, after topping 26,000 the week before, based on data reported by 5,000 hospitals from all states and territories.

The weekly hospitalization rate tumbled from 8 per 100,000 people to 4.5 per 100,000, which was still higher than any other December rate from all previous seasons going back to 2009-10, CDC data shows. 

Visits for flu-like illness represented 6.9% of all outpatient visits reported to the CDC during the week of Dec. 4-10. The rate reached 7.5% during the last full week of November before dropping to 7.3%, the CDC said.

There were 28 states or territories with “very high” activity for the latest reporting week, compared with 32 the previous week. Eight states – Colorado, Idaho, Kentucky, Nebraska, New Mexico, Oklahoma, Tennessee, and Washington – and New York City were at the very highest level on the CDC’s 1-13 scale of activity, compared with 14 areas the week before, the agency reported.

So far for the 2022-2023 season, the CDC estimated there have been at least 15 million cases of the flu, 150,000 hospitalizations, and 9,300 deaths. Among those deaths have been 30 reported in children, compared with 44 for the entire 2021-22 season and just 1 for 2020-21.

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

It’s beginning to look less like an epidemic as seasonal flu activity “appears to be declining in some areas,” according to the Centers for Disease Control and Prevention.

Declines in a few states and territories were enough to lower national activity, as measured by outpatient visits for influenza-like illness, for the second consecutive week. This reduced the weekly number of hospital admissions for the first time in the 2022-2023 season, according to the CDC influenza division’s weekly FluView report.

Flu-related hospital admissions slipped to about 23,500 during the week of Dec. 4-10, after topping 26,000 the week before, based on data reported by 5,000 hospitals from all states and territories.

The weekly hospitalization rate tumbled from 8 per 100,000 people to 4.5 per 100,000, which was still higher than any other December rate from all previous seasons going back to 2009-10, CDC data shows. 

Visits for flu-like illness represented 6.9% of all outpatient visits reported to the CDC during the week of Dec. 4-10. The rate reached 7.5% during the last full week of November before dropping to 7.3%, the CDC said.

There were 28 states or territories with “very high” activity for the latest reporting week, compared with 32 the previous week. Eight states – Colorado, Idaho, Kentucky, Nebraska, New Mexico, Oklahoma, Tennessee, and Washington – and New York City were at the very highest level on the CDC’s 1-13 scale of activity, compared with 14 areas the week before, the agency reported.

So far for the 2022-2023 season, the CDC estimated there have been at least 15 million cases of the flu, 150,000 hospitalizations, and 9,300 deaths. Among those deaths have been 30 reported in children, compared with 44 for the entire 2021-22 season and just 1 for 2020-21.

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

It’s beginning to look less like an epidemic as seasonal flu activity “appears to be declining in some areas,” according to the Centers for Disease Control and Prevention.

Declines in a few states and territories were enough to lower national activity, as measured by outpatient visits for influenza-like illness, for the second consecutive week. This reduced the weekly number of hospital admissions for the first time in the 2022-2023 season, according to the CDC influenza division’s weekly FluView report.

Flu-related hospital admissions slipped to about 23,500 during the week of Dec. 4-10, after topping 26,000 the week before, based on data reported by 5,000 hospitals from all states and territories.

The weekly hospitalization rate tumbled from 8 per 100,000 people to 4.5 per 100,000, which was still higher than any other December rate from all previous seasons going back to 2009-10, CDC data shows. 

Visits for flu-like illness represented 6.9% of all outpatient visits reported to the CDC during the week of Dec. 4-10. The rate reached 7.5% during the last full week of November before dropping to 7.3%, the CDC said.

There were 28 states or territories with “very high” activity for the latest reporting week, compared with 32 the previous week. Eight states – Colorado, Idaho, Kentucky, Nebraska, New Mexico, Oklahoma, Tennessee, and Washington – and New York City were at the very highest level on the CDC’s 1-13 scale of activity, compared with 14 areas the week before, the agency reported.

So far for the 2022-2023 season, the CDC estimated there have been at least 15 million cases of the flu, 150,000 hospitalizations, and 9,300 deaths. Among those deaths have been 30 reported in children, compared with 44 for the entire 2021-22 season and just 1 for 2020-21.

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